lignans and schizandrin

Topics: Anti-Inflammatory Agents; Antioxidants; Fruit; Lignans; Schisandra

Topics: China; Cyclooctanes; Lignans; Schisandra

There has been an exponential growth in the field of molecular oncology and cutting-edge research has enabled us to develop a better understanding of therapeutically challenging nature of cancer. Based on the mechanistic insights garnered from decades of research, puzzling mysteries of multifaceted nature of cancer have been solved to a greater extent. Our rapidly evolving knowledge about deregulated oncogenic cell signaling pathways has allowed us to dissect different oncogenic transduction cascades which play critical role in cancer onset, progression and metastasis. Pharmacological targeting of deregulated pathways has attracted greater than ever attention in the recent years. Henceforth, discovery and identification of high-quality biologically active chemicals and products is gaining considerable momentum. There has been an explosion in the dimension of natural product research because of tremendous potential of chemopreventive and pharmaceutical significance of natural products. Schisandrin is mainly obtained from Schisandra chinensis. Schisandrin has been shown to be effective against different cancers because of its ability to inhibit/prevent cancer via modulation of different cell signaling pathways. Importantly, regulation of non-coding RNAs by schisandrin is an exciting area of research that still needs detailed and comprehensive research.   However, we still have unresolved questions about pharmacological properties of schisandrin mainly in context of its regulatory role in TGF/SMAD, SHH/GLI, NOTCH and Hippo pathways.

Topics: Animals; Apoptosis; Carcinogenesis; Cell Movement; Clinical Trials as Topic; Cyclooctanes; Gene Expression Regulation, Neoplastic; Humans; Lignans; Neoplasms; Plant Extracts; Polycyclic Compounds; Protein Interaction Maps; Schisandra; Signal Transduction; Treatment Outcome

Multidrug resistance (MDR) is one of the major clinical challenges in cancer treatment and compromises the effectiveness of conventional anticancer chemotherapeutics. Among known mechanisms of drug resistance, drug efflux via ATP binding cassette (ABC) transporters, namely P-glycoprotein (P-gp) has been characterized as a major mechanism of MDR. The primary function of ABC transporters is to regulate the transport of endogenous and exogenous small molecules across the membrane barrier in various tissues. P-gp and similar efflux pumps are associated with MDR because of their overexpression in many cancer types. One of the intensively studied approaches to overcome this mode of MDR involves development of small molecules to modulate P-gp activity. This strategy improves the sensitivity of cancer cells to anticancer drugs that are otherwise ineffective. Although multiple generations of P-gp inhibitors have been identified to date, reported compounds have demonstrated low clinical efficacy and adverse effects. More recently, natural polyphenols have emerged as a promising class of compounds to address P-gp linked MDR. This review highlights the chemical structure and anticancer activities of selected members of a structurally unique class of 'biaryl' polyphenols. The discussion focuses on the anticancer properties of ellagic acid, ellagic acid derivatives, and schisandrins. Research reports regarding their inherent anticancer activities and their ability to sensitize MDR cell lines towards conventional anticancer drugs are highlighted here. Additionally, a brief discussion about the axial chirality (i.e., atropisomerism) that may be introduced into these natural products for medicinal chemistry studies is also provided.

Topics: Animals; Cyclooctanes; Drug Discovery; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Ellagic Acid; Humans; Lignans; Neoplasms; Polycyclic Compounds; Polyphenols

With increasing use of pharmaceuticals, drug-induced liver injury (DILI) has become a significant therapeutic challenge to physicians all over the world. Drugs based on Schisandra fruits (SF for short, the fruits of Schisandra chinensis or Schisandra sphenanthera) or synthetic analogues of schisandrin C, are commonly prescribed for treating DILI in China.. This review summarizes the literature regarding the application of SF-derived drugs in patients with DILI and current understanding of mechanisms underlying the protective effects of SF against liver injury.. Keywords related to drug-induced liver injury and Schisandra fruits were searched in the following databases: Pubmed, Cochrane Library, Google Scholar, LiverTox, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal database (VIP), and Wanfang database. All studies, published in English or Chinese, were included. Clinical study exclusion criteria: if patients received other Chinese herbal medicines in a study, the study will not be included in this review.. Clinical studies have shown that SF-derived drugs are effective in inhibiting drug-induced elevation of serum levels of alanine aminotransferase, aspartate transaminase and total bilirubin. Cellular and animal studies have demonstrated that crude SF extracts, lignan compounds found in SF, and SF-derived drugs are effective in protecting the liver against xenobiotic-induced injury. Regulation of cytochrome P450 enzyme activity, anti-oxidation, anti-inflammation and acceleration of liver regeneration are involved in the hepatoprotective mechanisms of SF.. SF-derived drugs are effective in ameliorating DILI in China. To verify the clinical efficacy of these drugs, high-quality clinical studies are needed.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; China; Cyclooctanes; Drugs, Chinese Herbal; Fruit; Humans; Lignans; Liver; Liver Regeneration; Phytotherapy; Polycyclic Compounds; Schisandra

Schisandra chinensis (TURCZ.) BAILL., originally a Japanese-Manchurian endemite, yields a vegetable drug (Schisandrae fructus) with a number of very utilizable therapeutic effects. The paper reports the results of phytochemical and pharmacological-toxicological studies approximately from the year 1990 carried out both with the drug and, in particular, the principal isolated lignans of the dibenzo[a,c]cyclooctadiene type. The results confirm the validity of the historical use of the drug, in particular as a hepatoprotective, adaptogenic, and antioxidative agent. It is obvious that a very positive therapeutic effect based on the use of a complex mixture of its principal constituents because their biological effects are complementary and potentiate each other. At the same time, some lignans (e.g. gomisin A, gomisin N) are interesting as new prospective medicines.

Topics: Cardiovascular Diseases; Cyclooctanes; Humans; Lignans; Plant Extracts; Plants, Medicinal; Polycyclic Compounds

Fructus Schizandrae sinensis Baill, a traditional Chinese medicine, used as tonic and sedative, has been shown at the beginning of 70's to lower the elevated serum glutamic-pyruvic transaminase (SGPT) levels of patients suffering from chronic viral hepatitis. During past 20 years, a series of neolignans have been isolated and identified as effective principles. Pharmacological studies revealed that they increased liver protein and glycogen synthesis, antagonized liver injuries from CCl4 and thioacetamide. The mechanism of SGPT lowering was considered as a hepato-protective and membrane stabilize action, although inhibition of the activity of liver GPT may also be existed. It was found that some principles of Schizandrae have an inducing effect on hepatic microsomal drug-metabolizing enzyme system P-450, thus explained their anti-toxic, anti-carcinogenic and anti-mutagenic effects. A synthetic derivative compound of Schisandrin called DDB has most of the above mentioned actions now used widely in China as a hepato-protective drug with high effectiveness in normalizing liver functions and very low side effects. From natural Schisandrin to synthesized DDB, pointed out a successful way in the development of new drugs from natural products.

Topics: Alanine Transaminase; Animals; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Humans; Lignans; Lignin; Liver; Polycyclic Compounds

Topics: Animals; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Cyclooctanes; Cytochrome P-450 Enzyme System; Drugs, Chinese Herbal; Lignans; Liver; Mitochondria, Liver; Polycyclic Compounds

Ginseng Radix et Rhizoma (GRR) and Schisandrae Chinensis Fructus (SCF) are frequently used as herb pairs in traditional herbal formulas especially for the synergetic beneficial effects on lung and heart. Shengmai-yin (SMY), a noted formula, was first published in the traditional Chinese medicine classic named Yixue Qiyuan written by Zhang Yuansu in the Jin Dynasty, and has been used for deficiency of both qi and yin, palpitation, shortness of breath and spontaneous sweating. In SMY, GRR, a sovereign herb, plays an essential role in tonifying lung and supplementing qi, and SCF as an adjuvant herb contributes to the effects of nourishing yin and promoting fluid production, both of which are traditionally used as invigorants in China, Korea, Japan, and Russia. However, the underlying compatibility mechanism of GRR-SCF has remained unknown.. In order to explore the impact and underlying mechanism of schisandra chinensis extract (SCE) on the absorption of ginsenosides Rb. Preliminarily, pharmacokinetic characteristics of ginseng extract (GE) in the presence and absence of SCE were studied. Thereafter, molecular docking was used to predict whether ginsenosides were P-glycoprotein (P-gp) or cytochrome P450 isoenzyme 3A4 (CYP3A4) substrates. Finally, the effects and underlying mechanism of SCE on the absorption of GE were further investigated by in situ SPIP experiment.. Our findings indicated that SCE could increase exposure in vivo and the intestinal absorption of distinct ginsenosides. Additionally, we found that the PPD-type ginsenosides Rb. The study demonstrated that SCE could improve the absorption of GE, and revealed the underlying compatibility mechanism of GRR and SCF from the perspective of P-gp and CYP3A4-mediated interactions to some extent, which provided a certain scientific reference for the compatibility and clinical practice of GRR-SCF as common herb pairs in traditional prescriptions such as SMY. Moreover, this study also furnished a strategy for improving the oral bioavailability of different types of ginsenosides by drug combinations.

Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cytochrome P-450 CYP3A; Ginsenosides; Lignans; Molecular Docking Simulation; Plant Extracts; Schisandra

Schisandrin B (Scheme B) is the most abundant and active lignan monomer isolated from Schisandra chinensis. At present, most reports focus on its cardioprotective and hepatoprotective effects, however, the related reports on gastrointestinal protective effects are still limited. The study aims to evaluate the protective effect of Scheme B on cisplatin-induced rat intestinal crypt epithelial (IEC-6) cell injury and the possible molecular mechanisms. The results showed that Scheme B at 2.5, 5 and 10 μM could inhibit dose-dependently the reduction of cell activity induced by cisplatin exposure at 1 μM, decrease the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while increasing glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) to alleviate oxidative stress injury in IEC-6 cell lines. Meanwhile, Scheme B could relieve cisplatin-induced apoptosis by regulating PI3K/AKT and the downstream caspase signaling pathway. The results from flow cytometry analysis and mitochondrial membrane potential (MMP) staining also demonstrated the anti-apoptosis effect of Scheme B. Furthermore, Scheme B was found to reduce the inflammation associated with cell damage by evaluating the protein expressions of the nuclear factor-kappa B (NF-κB) signaling pathway. Importantly, Wnt/β-catenin, as a functional signaling pathway that drives intestinal self-recovery, was also in part regulated by Scheme B. In conclusion, Scheme B might alleviate cisplatin-induced IEC-6 cell damage by inhibiting oxidative stress, apoptosis, inflammation, and repairing intestinal barrier function. The present research provides a strong evidence that Scheme B may be a useful modulator in cisplatin-induced intestinal toxicity.

Topics: Animals; Cisplatin; Glutathione; Inflammation; Lignans; NF-kappa B; Oxidative Stress; Phosphatidylinositol 3-Kinases; Rats; Schisandra

Schisandra chinensis is a potential plant for production of nutrient supplements due to adaptogens content. The dominant bioactive substance, lignan schisandrin, has positive effects on human health, but it can cause possible allelopathic effects in relation to other plants. S. chinensis is not native to European ecosystems, and its ecotoxicological properties have not been verified yet. Lemna minor was selected as a model aquatic plant to test its potential impact on the aquatic environment. Crude water extract from S. chinensis fruits, simulating the natural soaking of active substances in a surface water body, was used in treatments from 0.045 to 45 mg/L (according to the content of schisandrin as the dominating lignan). During seven days of cultivation, the growth (number of plants, leaf area, fresh weight) and photosynthetic activity of L. minor fronds were assessed. In low treatments (0.045 and 0.09 mg/L), the extract of S. chinensis did not cause any changes in duckweed growth parameters or photosynthetic performance. Higher treatments (0.45 and 0.9 mg/L) caused significant limitations in plants' number, total leaf area, and fresh weight. The photosynthetic parameters (basal chlorophyll fluorescence, quantum yields) were affected only by 0.9 mg/L. The highest treatment, 45 mg/L, exhibited extreme toxicity to duckweed plants causing their death during the first five days of cultivation. Schisandrin and other bioactive substances extractable from S. chinensis fruits can negatively impact water biota in the case of massive contamination of surface water.

Topics: Ecosystem; Humans; Lignans; Schisandra; Water; Water Pollutants, Chemical

From the fruits of Schisandra cauliflora, five new dimethylbutyrylated dibenzocyclooctadiene lignans, named schisandracaurins A-E, were isolated using separation and chromatographic techniques. Their structures were determined by extensive analyses of HR-ESI-MS, NMR, and ECD spectra. The schisandracaurins A-E potentially inhibited NO production in LPS-activated RAW264.7 cells with their IC

Topics: Cyclooctanes; Fruit; Lignans; Lipopolysaccharides; Molecular Structure; Schisandra

Plants of the Schisandra genus are commonly used in folk medicinal remedies. Some Schisandra species and their lignans have been reported to improve muscle strength. In the present study, four new lignans, named schisacaulins A-D, together with three previously described compounds ananonin B, alismoxide, and pregomisin were isolated from the leaves of S. cauliflora. Their chemical structures were determined by extensive analyses of HR-ESI-MS, NMR, and ECD spectra. Schisacaulin D and alismoxide significantly stimulated skeletal muscle cell proliferation by increasing the number of fused myotubes and expression of myosin heavy chain (MyHC) which may be good candidates for the treatment of sarcopenia.

Topics: Cell Proliferation; Lignans; Muscle, Skeletal; Plant Leaves; Schisandra

Topics: Animals; Collagen; Lignans; Mice; Polycyclic Compounds; Pulmonary Fibrosis

To investigate the volatile components of

Topics: Fruit; Lignans; Plant Extracts; Schisandra

Acute lung injury (ALI) is characterized by an excessive inflammatory response, closely related to sepsis occurrence and development. It has been reported that Schisandrin (Sch) exhibits anti-inflammatory activity. However, whether the beneficial effects of Sch exists during ALI remains to be studied. In this study, the impact of Sch was evaluated by studying lung tissue damage, measuring the concentrations of pro-inflammatory factors, and the expression of apoptotic proteins in the LPS-induced ALI mice model. Protein expression of inflammation-related signaling pathway within the lung tissue and A549 cells were also measured. In addition, the effect of Sch on A549 cell apoptosis and inflammatory markers was also detected. Animal experiments demonstrated that pre-feeding Sch alleviated the production of inflammation mediators, abnormal pathological injuries, and blocked the progression of apoptotic events in the lung tissue. The in vitro experiments showed that Sch pretreatment reduced LPS upregulated interleukin-1β (IL-1β), IL-18, and IL-6 levels, and improved LPS-induced abnormal apoptosis. Sch and the pathway inhibitor AG490 also inhibited the expression levels of p-JAK2 and p-STAT3 in A549 cells. Moreover, pretreatment with Sch significantly inhibited the activation of NLRP3 inflammasomes, reduced inducible nitric oxide synthase, and cyclooxygenase 2 proteins expression during ALI in vitro and in vivo. Overall, Sch effectively alleviated ALI and provided a new mechanism to support the protective effect of Sch for sepsis-induced ALI. PRACTICAL IMPLICATIONS: ALI is characterized by inflammatory injury of the lungs, which is an important cause of high morbidity and mortality in severe patients. Sch is considered as a botanical active ingredient with various pharmacological activities, such as neuroprotective and vascular protective effects. However, the effect of Sch on ALI and its mechanism remains largely unknown. Research data indicate that Sch exerts an anti-inflammatory effect by reducing the production of inflammatory factors and abnormal apoptosis of cells, further alleviating lung damage. The protective effect of Sch was associated with inhibition of the activation of NLRP3 and the JAK2/STAT3 inflammatory pathways. The study, therefore, confirmed that Sch has a potential as an effective drug to prevent ALI diseases.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Cyclooctanes; Lignans; Lipopolysaccharides; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Polycyclic Compounds; Sepsis

Topics: Cyclooctanes; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dioxoles; Drug Interactions; Humans; Immunosuppressive Agents; Lignans; Models, Biological; Polycyclic Compounds; Tacrolimus

Quality control of Traditional Chinese Medicines (TCMs) has improved greatly, but there is still a lack of a convincing quality evaluation system for TCMs. Developing quality control markers of TCMs based on pharmacodynamics instead of content has been an attractive approach. However, on account of neglecting phytochemistry attributes of TCMs, part of effective markers might be short of specificity and inconvenient for detecting in production manufacture, which is adverse to control the quality of TCMs systematically.. To build a novel and multidimensional quality assessment approach for TCMs based on pharmacodynamics and chemical properties.. Schisandra chinensis (Turcz.) Baill (S. chinensis) was used as an example and a rat depression model was built by using a chronic unpredictable mild stress procedure. For identifying the antidepressive components of S. chinensis, we elucidated its antidepressant mechanism in first-step by using quantitative RT-PCR and immunoblotting techniques. And accordingly, correlation analysis between ingredients in vivo with target proteins and anti-inflammation experiments in vitro were carried out. On the other hand, HPLC fingerprint combinations with diverse chemometrics methods were applied to analyze 14 preparations of S. chinensis to obtain its characteristic chemical information. Finally, we ascertained the quality control markers of S. chinensis by integrating the efficacious and characteristic constituents.. Our research indicated that S. chinensis treated depression by relieving disordered monoaminergic system and ameliorating neuroinflammation. Five effective substances (schisandrol A, schisandrin A, gomisin N, schisandrin B, and schisandrin C) were screened out according to their potential anti-depression efficacy. Besides, 21 common ingredients and 4 representative constituents of S. chinensis were identified by chemical analysis, whereas only 2 characteristic quantitative markers (schisandrol A, schisandrol B) were ultimately ascertained based on previous studies.. 6 components, schisandrol A, schisandrin A, gomisin N, schisandrin B, schisandrin C, and schisandrol B, possessed efficacy, measurability, and specificity, were selected as the comprehensive markers for quality control of S. chinensis. We proposed a multidimensional strategy for identifying comprehensive quality markers for TCMs in this study.

Topics: Animals; Biomarkers; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Lignans; Polycyclic Compounds; Rats; Schisandra

Lignan schisandrol A (SolA) is known to have antioxidant and anti-inflammatory effects. However, the impact of SolA on obesity is poorly understood. To test the hypothesis that SolA has anti-obesity effects, C57BL/6J mice were fed a high-fat diet with or without SolA (0.006%, w/w) for 16 weeks. SolA decreased visceral fat mass (10%) by increasing energy expenditure and upregulating white adipose tissue thermogenic genes mRNA expression. Furthermore, SolA upregulated adipose Lpl mRNA expression and decreased plasma free fatty acid (FFA), triglyceride (TG), apolipoprotein (apo) B, aspartate aminotransferase levels and TG/HDL-cholesterol and apoB/apoA1 ratios as well as hepatic lipid droplets. Increased hepatic β-oxidation and fecal FFA and TG levels were observed in the SolA-supplemented mice, suggesting an association of its lipid-lowering effect with increased hepatic β-oxidation, fecal fat excretion and adipose Lpl. Conclusionally, this study provides evidence on the protective effects of SolA against adiposity, dyslipidemia and nonalcoholic fatty liver disease in obese mice.

Topics: Animals; Diet, High-Fat; Lignans; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; RNA, Messenger

In this study, roasting was applied to enhance the volatile compound content and antioxidant activity of hot-air dried omija (Schisandra chinensis Baillon) fruit. The major volatile compounds were furfural, 1,8-cineole and terpinen-4-ol. Total volatile compound concentration in omija roasted at 150 ℃ for 15 min was approximately 4 times higher than that in hot-air dried omija. Contents of monoterpenes and sesquiterpenes in roasted omija were significantly increased, compared to that of the hot-air dried omija (P < 0.05). The contents of schizandrin in extracts of hot-air dried omija and omija roasted at 150 ℃ for 10 min were determined to be 28.9 and 106.5 mg/100 g extract, respectively. The content of gomisin A from roasted omija was about 5 times higher than that of hot-air dried omija. Through this study, it is believed that the usability of omija will be expanded.

Topics: Cooking; Cyclooctanes; Dioxoles; Flavonoids; Fruit; Lignans; Plant Extracts; Polycyclic Compounds; Polyphenols; Schisandra; Temperature; Volatile Organic Compounds

Recently, a new drug combination GRS comprising ginsenoside Rb1 (G-Rb1), ruscogenin (R-Rus) and schisandrin (S-SA) was screened based on ShengMai preparations, which exhibited a prominent cardioprotective effects against myocardial ischemia/reperfusion (MI/R) injury.. To investigate their systemic and individual mechanism of each compound in combination GRS.. The mice model of MI/R and hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury were performed to explore the respective characteristics of each compound in GRS against myocardial injury.. Each component in the combination GRS attenuated MI/R injury as evidenced by decreased myocardial infarct size, ameliorated histological features, and improved biochemical indicators. Meanwhile, ingredient G, R and S in combination also individually performed a significant decrease of apoptotic index in MI/R mice and H/R-induced cardiomyocytes injury. Mechanistically, component G in GRS could markedly increase the ATP content in cardiomyocytes through activation of AMPKα phosphorylation. Interestingly, the anti-apoptotic actions of G were profoundly attenuated by knockdown of AMPKα, while no alteration was observed on composition R and S. Moreover, component R in GRS significantly reduced the IL-6 and TNF-α mRNA expression, as well as the content of IL-6 via the modulation of NF-κB signaling pathway. Further, component S exhibited the most powerful anti-oxidative capacity in GRS and remarkably decreased the production of MDA and ROS, and potential mechanisms might at least in part through activating the Akt-14-3-3 signaling pathway and inhibiting the phosphorylation of Bad and ERK1/2.. Our results indicated that the respective mechanism of each compound in combination GRS against MI/R injury might closely associated with energy metabolism modulation, suppression of inflammation and oxidative stress.

Topics: Animals; Cell Line; Cell Survival; Cyclooctanes; Drug Combinations; Drugs, Chinese Herbal; Ginsenosides; Inflammation Mediators; Lignans; Male; Mice; Mice, Inbred ICR; Myocardial Reperfusion Injury; Myocytes, Cardiac; Polycyclic Compounds; Rats; Spirostans; Treatment Outcome

Schisandrin which is derived from Schisandra chinensis has shown multiple pharmacological effects on various diseases including Alzheimer's disease (AD). It is demonstrated that mitochondrial dysfunction plays an essential role in the pathogenesis of neurodegenerative disorders.. Our study aims to investigate the effects of schisandrin on mitochondrial functions and metabolisms in primary hippocampal neurons.. In our study, rat primary hippocampal neurons were isolated and treated with indicated dose of amyloid β1-42 (Aβ1-42) oligomer to establish a cell model of AD in vitro. Schisandrin (2 μg/mL) was further subjected to test its effects on mitochondrial function, energy metabolism, mitochondrial biogenesis, and dynamics in the Aβ1-42 oligomer-treated neurons.. Our findings indicated that schisandrin significantly alleviated the Aβ1-42 oligomer-induced loss of mitochondrial membrane potential and impaired cytochrome c oxidase activity. Additionally, the opening of mitochondrial permeability transition pore and release of cytochrome c were highly restricted with schisandrin treatment. Alterations in cell viability, ATP production, citrate synthase activity, and the expressions of glycolysis-related enzymes demonstrated the relief of defective energy metabolism in Aβ-treated neurons after the treatment of schisandrin. For mitochondrial biogenesis, elevated expression of peroxisome proliferator-activated receptor γ coactivator along with promoted mitochondrial mass was found in schisandrin-treated cells. The imbalance in the cycle of fusion and fission was also remarkably restored by schisandrin. In summary, this study provides novel mechanisms for the protective effect of schisandrin on mitochondria-related functions.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Animals, Newborn; Cyclooctanes; Cytochromes c; Energy Metabolism; Hippocampus; Lignans; Membrane Potential, Mitochondrial; Mitochondria; Mitochondrial Dynamics; Models, Biological; Neurons; Neuroprotective Agents; Organelle Biogenesis; Peptide Fragments; Polycyclic Compounds; Primary Cell Culture; Rats, Sprague-Dawley

Ninjin'yoeito (NYT), a Japanese traditional Kampo medicine, has been reported to exert various clinical benefits such as relief from fatigue, malaise, anorexia, frailty, sarcopenia, and cognitive dysfunction. Recently, some review articles described the pharmacological effects of NYT and additionally indicated the possibility that multiple ingredients in NYT contribute to these effects. However, pharmacokinetic data on the ingredients are essential in addition to data on their pharmacological activities to accurately determine the active ingredients in NYT.. This study assessed the in vivo pharmacokinetics of NYT using mice.. Target liquid chromatography-mass spectrometry (LC-MS) and wide target LC-MS or LC-tandem MS of NYT ingredients in plasma and the brain after oral administration of NYT were performed. Imaging MS was performed to investigate the detailed brain distributions of NYT ingredients.. The concentrations of 13 ingredients in plasma and schizandrin in the brain were quantified via target LC-MS, and the wide target analysis illustrated that several ingredients are absorbed into blood and transported into the brain. Imaging MS revealed that schizandrin was homogenously dispersed in the NYT-treated mouse brain.. These results should be useful for clarifying the active ingredients of NYT and their mechanisms of actions.

Topics: Administration, Oral; Animals; Brain; Chromatography, Liquid; Cyclooctanes; Drugs, Chinese Herbal; Lignans; Male; Mass Spectrometry; Mice; Mice, Inbred C57BL; Polycyclic Compounds; Tissue Distribution

Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. The virulence of an intracellular human pathogen

Topics: Azithromycin; Biological Assay; Chlamydophila pneumoniae; Cyclooctanes; Glutathione; Humans; Kinetics; Lignans; Macrophages; Oxidation-Reduction; Phenotype; Polycyclic Compounds; Reactive Oxygen Species; THP-1 Cells

Avian pathogenic Escherichia coli (APEC) is a kind of highly pathogenic parenteral bacteria, which adheres to chicken type II pneumocytes through pili, causing inflammatory damage of chicken type II pneumocytes. Without affecting the growth of bacteria, anti-adhesion to achieve anti-inflammatory effect is considered to be a new method for the treatment of multi-drug-resistant bacterial infections. In this study, the anti-APEC activity of schizandrin was studied in vitro. By establishing the model of chicken type II pneumocytes infected with APEC-O78, the adhesion number, the expression of virulence genes, the release of lactate dehydrogenase (LDH), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8 and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were detected. The results showed that schizandrin reduced the release of LDH and the adherence of APEC on chicken type II pneumocytes. Moreover, schizandrin markedly decreased the levels of IL-1β, IL-8, IL-6, and TNF-α, the mechanism responsible for these effects was attributed to the inhibitory effect of schizandrin on NF-κB and MAPK signaling activation. In conclusion, our findings revealed that schizandrin could reduce the inflammatory injury of chicken type II pneumocytes by reducing the adhesion of APEC-O78 to chicken type II pneumocytes. The results indicate that schizandrin can be a potential agent to treat inflammation caused by avian colibacillosis.

Topics: Alveolar Epithelial Cells; Animals; Anti-Inflammatory Agents; Bacterial Adhesion; Cells, Cultured; Chickens; Cyclooctanes; Cytokines; Escherichia coli; Escherichia coli Infections; Extracellular Signal-Regulated MAP Kinases; Inflammation; Inflammation Mediators; L-Lactate Dehydrogenase; Lignans; NF-kappa B; Polycyclic Compounds; Poultry Diseases; Signal Transduction

Topics: Animals; Apoptosis; Cardiotonic Agents; Cell Line; Cyclooctanes; Enzymes; Lignans; Male; Metabolomics; Mice, Inbred ICR; Myocardial Ischemia; Myocardium; Myocytes, Cardiac; Polycyclic Compounds; Protein Interaction Maps; Rats; Signal Transduction

Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens elderly health. Schisandrin (SCH) and nootkatone (NKT) are two core components derived from Alpinia oxyphylla-Schisandra chinensis herb pair (ASHP), a traditional Chinese medicine formulation. Previous studies demonstrated that the combination of NKT and SCH exerted a neuroprotective effect in AD mouse models. The present study was undertaken to investigate whether there was a synergistic effect between NKT and SCH and the possible mechanism in Aβ1-42 induced PC12 cells. SCH (50 μM) and NKT (10 μM) had the most notable inhibitory effect on the level of Aβ secreted by cells. Treatment with NKT + SCH activated the PI3K/AKT/Gsk-3β/mTOR pathway. Inflammation related proteins such as NF-κB, IKK, IL-1β, IL-6 and TNF-α were decreased. The levels of cleaved-Caspase3 and LC3-II were reduced, indicating that apoptosis and autophagy were inhibited. These results revealed that NKT + SCH exerted a neuroprotective effect via the PI3K/AKT pathway, inhibiting inflammation, apoptosis and autophagy.

Topics: Alzheimer Disease; Animals; Apoptosis; Autophagy; Cyclooctanes; Disease Models, Animal; Drug Synergism; Inflammation; Lignans; Mice; Neuroprotective Agents; PC12 Cells; Phosphatidylinositol 3-Kinases; Polycyclic Compounds; Polycyclic Sesquiterpenes; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction; tau Proteins

Schisandrin, an active component extracted from Schisandra chinensis (Turcz.) Baill has been reported to alleviate the cognitive impairment in neurodegenerative disorder like Alzheimer's disease (AD). However, the mechanism by which schisandrin regulates the cognitive decline is still unclear. In our study, intracerebroventricular injection of streptozotocin (STZ) was employed to establish AD model in male Wistar rats, and indicated dose of schisandrin was further administered. The Morris water maze test was performed to evaluate the ability of learning and memory in rats with schisandrin treatment. The results indicated that schisandrin improved the capacity of cognition in STZ-induced rats. The contents of pro-inflammatory cytokines in brain tissue were determined by ELISA, and the expressions of these cytokines were assessed by western-blot and immunohistochemistry. The results showed that treatment of schisandrin significantly reduced the production of inflammation mediators including tumor necrosis factor-α, interleukin-1β and interleukin-6. Further study suggested a remarkable decrease in the expressions of ER stress maker proteins like C/EBP-homologous protein, glucose-regulated protein 78 and cleaved caspase-12 in the presence of schisandrin, meanwhile the up-regulation of sirtuin 1 (SIRT1) was also observed in the same group. Additionally, the results of western-blot and EMSA demonstrated that schisandrin inhibited NF-κB signaling in the brain of STZ-induced rats. In conclusion, schisandrin ameliorated STZ-induced cognitive dysfunction, ER stress and neuroinflammation which may be associated with up-regulation of SIRT1. Our study provides novel mechanisms for the neuroprotective effect of schisandrin in AD treatment.

Topics: Alzheimer Disease; Animals; Cognition; Cognitive Dysfunction; Cyclooctanes; Disease Models, Animal; Endoplasmic Reticulum Stress; Lignans; Male; Phytotherapy; Polycyclic Compounds; Rats, Wistar; Schisandra; Sirtuin 1; Streptozocin; Up-Regulation

Xiaosheng prescription (XSP) has been used for dry eye disease (DED) for more than 10 years in Eye Hospital of China Academy of Chinese Medicine Sciences. However, the effective ingredients involved have remained unclear, which was investigated in this study by the correlation of ingredient and therapeutic activity. Human corneal epithelial cells (HCEC) cultured with 110 mM NaCl solution in vitro and C57BL/6 mice injected subcutaneously with scopolamine hydrobromide were used to establish dry eye models, and the therapeutic effect of XSP extract 1 was better than that of XSP extract 2 significantly. Then, UPLC-Q-TOF/MS and data analysis program Progenesis QI and Makerlynx XS were used to analyze the potential effective ingredients of XSP, and 4 compounds were speculated and identified, in which Schisandrin and 1 μM of Schisantherin A could obviously increase the cell survival rate of injured cells on the cell model. It can be indicated that Schisandrin and Schisantherin A are probably the potential effective ingredients in XSP for DED.

Topics: Animals; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Epithelium, Corneal; Female; Humans; Lignans; Mice; Plant Extracts; Polycyclic Compounds

A wide variety of plant raw materials thought to promote health are used as herbal medicines as well as foods. However, there is no legal maximum or minimum concentration limit on any herbal compound when these plant raw materials are used in processed foods. Legally, these processed foods are regulated only for harmful substances, and there is no other guarantee of their contents. Therefore, the objective of this study was to determine the concentrations of 12 herbal compounds (nodakenin, decursin, decursinol angelate, morroniside, loganin, glycyrrhizic acid, liquiritigenin, puerarin, daidzin, schisandrin, gomisin A, gomisin N) in commonly used plant raw materials, such as "Angelica Gigas root", "Cornus Fruit", "Liquorice Root", "Pueraria Root", and "Schisandra Fruit"; and also in 45 processed foods, using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Method validation was performed successfully using the parameters of specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, matrix effect, extraction recovery, and stability. The 12 herbal compounds were determined to be present in all the foods advertised as containing each ingredient, although in very low concentrations in some cases. Three solid samples labelled as 100% pure material from one herbal species also contained herbal compounds found in others, so that intentional or unintentional adulteration was suspected.

Topics: Benzopyrans; Butyrates; Chromatography, Liquid; Coumarins; Cyclooctanes; Dioxoles; Flavanones; Food Analysis; Fruit; Glucosides; Glycosides; Glycyrrhizic Acid; Herbal Medicine; Iridoids; Isoflavones; Lignans; Plant Roots; Plants, Medicinal; Polycyclic Compounds; Tandem Mass Spectrometry

Growing evidence shows that gut microbiota and neuroinflammatory responses play a critical role in the pathogenesis of depression. Our previous study demonstrated that schisandrin (SCH) could reduce proinflammatory factors of depressive mice. Therefore, our present study is to research the potential connection between gut microbial and anti-inflammatory effects of SCH on a depressive mouse model induced by lipopolysaccharide (LPS). We found that SCH pre-treatment could decrease the immobility time of forced swimming test (FST) and tail suspension test (TST). And the results of 16S rRNA demonstrated that SCH pre-administration attenuated the dysbiosis of gut microbiota of depressive mice, along with altered fecal short-chain fatty acids (SCFAs). Furthermore, SCH reduced the levels of proinflammatory factors of depressive mice and the expression of TLR4/NF-κB signaling pathway in the hippocampus. Overall, our study indicated that SCH might recover the gut microbial disorder of depressive mice through suppressing the expression of TLR4/NF-κB signaling pathway.

Topics: Animals; Anti-Inflammatory Agents; Antidepressive Agents; Bacteria; Behavior, Animal; Cyclooctanes; Cytokines; Depression; Disease Models, Animal; Dysbiosis; Fatty Acids, Volatile; Gastrointestinal Microbiome; Hippocampus; Host-Pathogen Interactions; Inflammation Mediators; Lignans; Lipopolysaccharides; Male; Mice, Inbred C57BL; Motor Activity; NF-kappa B; Polycyclic Compounds; Signal Transduction; Toll-Like Receptor 4

We established a mouse model of allergic asthma by sensitizing with chicken ovalbumin. The volatile oils and decoctions from raw, wine- and vinegar-steamed Schisandra chinensis fruits were intragastrically administrated to the mice. Atomization, serum IgE, IL-2, IL-4 and IFN-γ in the lung homogenates and pathological sections were evaluated to compare the effect of these volatile oils and decoctions on allergic asthma in mice. The results showed that all Schisandra volatile oils could significantly suppress allergic asthma in mice. Raw Schisandra volatile oil was most effective followed by volatile oils extracted from wine-steamed and vinegar-steamed Schisandra. The decoctions had no significant impact. Our findings demonstrated that volatile oil was the active ingredient in Schisandra, and raw Schisandra could be used to prevent cough and asthma.

Topics: Animals; Asthma; Cyclooctanes; Fruit; Hypersensitivity; Lignans; Male; Mice; Oils, Volatile; Ovalbumin; Plant Extracts; Polycyclic Compounds; Schisandra

One new sesquiterpene (α-iso-cubebenol acetate,

Topics: Animals; Cyclooctanes; Dioxoles; Feeding Behavior; Lignans; Plant Stems; Polycyclic Compounds; Schisandra; Sesquiterpenes; Structure-Activity Relationship; Tribolium; Triterpenes

Topics: Alzheimer Disease; Animals; Cyclooctanes; Disease Models, Animal; Glutathione; Lignans; Malondialdehyde; Maze Learning; Mice; Neuroprotective Agents; Oxidative Stress; Plant Extracts; Polycyclic Compounds; Polycyclic Sesquiterpenes; Superoxide Dismutase

The neuroprotective role of schizandrin (SA) in cerebral ischemia-reperfusion (I/R) was recently highlighted. However, whether SA plays a regulatory role on autophagy in cerebral I/R injury is still unclear. This study aimed to explore whether the neuroprotective mechanisms of SA were linked to its regulation of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/autophagy pathway in vivo and in vitro. The present study confirmed that SA significantly improved oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced PC12 cells injury. The results of immunoblotting and confocal microscope showed that SA decreased autophagy in OGD/R-injured PC12 cells, which was reflected by the decreased Beclin-1 and LC3-II expression, autophagy flux level, and LC3 puncta formation. In addition, the autophagy inducer rapamycin partially prevented the effects of SA on cell viability and autophagy after OGD/R, whereas the autophagy inhibitor 3-methyladenine (3-MA) exerted the opposite effect. The results of Western blotting showed that SA markedly decreased the phosphorylation of AMPK (p-AMPK), whereas the phosphor-mTOR (p-mTOR) levels increased in the presence of OGD/R insult. Furthermore, pretreatment with the AMPK inducer AICAR partially reversed the protective effects and autophagy inhibition of SA. However, AMPK inhibitor Compound C pretreatment further promoted the inhibition of SA on autophagy induction and cell damage induced by OGD/R. Taken together, these findings demonstrate that SA protects against OGD/R insult by inhibiting autophagy through the regulation of the AMPK-mTOR pathway and that SA may have therapeutic value for protecting neurons from cerebral ischemia.

Topics: AMP-Activated Protein Kinases; Animals; Autophagy; Cyclooctanes; Disease Models, Animal; Glucose; Lignans; Mice; Models, Biological; Molecular Structure; Neurons; Neuroprotective Agents; Oxidation-Reduction; Oxygen; Polycyclic Compounds; Rats; Reperfusion Injury; Signal Transduction; Stroke; TOR Serine-Threonine Kinases

Arboreous fruit of Schisandra chinensis Baillon, Schisandra Fruit (SF), is a crude drug used in Japanese traditional Kampo medicine. The marker compounds of SF for quality control are lignans, such as schizandrin (Sz) and gomisin A (GmA). Kampo formulation containing SF is usually prepared as decoctions in the dosage form of whole crude drug (W), as its size is small enough to measure using a spoon. However, in some traditional books, it has been described that SF must be used in the dosage form of crushed or cut pieces (Cr). In this study, we evaluated the transferring ratio of lignans from SF to the decoction, and the stability and taste of the decoctions of shoseiryuto (SST) and ninjin'yoeito (NYT) using each dosage form, i.e., Cr and W, of SF. The transferring ratio of Sz and GmA was significantly higher in the decoction prepared with the Cr form than that prepared using the W form in both SST and NYT. The concentration of Sz and GmA in the decoctions was stable when maintained at 4 °C for 35 days. The taste of SST decoction prepared using the Cr form was more acidic, harsher, and bitterer than SST decoction prepared using the W form, and the taste of NYT decoction prepared using the Cr form was harsher than NYT decoction prepared using the W form. In conclusion, when SF is used in Kampo prescription, crushing the fruits and seeds can increase its effectiveness.

Topics: Adult; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Female; Fruit; Humans; Lignans; Male; Medicine, Kampo; Polycyclic Compounds; Schisandra; Taste; Young Adult

Redox signaling has been established as an essential component of inflammatory responses, and redox active compounds are of interest as potential immunomodulatory agents. Dibenzocyclooctadiene lignans isolated from Schisandra chinensis, a medicinal plant with widespread use in oriental medicine, have been implicated to possess immunomodulatory properties but their effects on the human innate immune system cells have not been described. In this contribution, data are presented on the impact of schisandrin, schisandrin B and schisandrin C on human monocytic cell redox status, as well as their impact on dendritic cell maturation and T cell activation capacity and cytokine production. In THP-1 cells, levels of intracellular reactive oxygen species (ROS) were elevated after 1 h exposure to schisandrin. Schisandrin B and schisandrin C decreased cellular glutathione pools, which is a phenotype previously reported to promote anti-inflammatory functions. Treatment of human primary monocytes with the lignans during their maturation to dendritic cells did not have any effect on the appearance of surface markers HLA-DR and CD86 but schisandrin B and schisandrin C suppressed the secretion of cytokines interleukin (IL)-6, IL-10 and IL-12 by the mature dendritic cells. Dendritic cells maturated in presence of schisandrin C were further cocultured with naïve CD4+ T cells, resulting in reduced IL-12 production. In THP-1 cells, schisandrin B and schisandrin C reduced the IL-6 and IL-12 production triggered by E. coli lipopolysaccharide and IL-12 production induced by an infection with Chlamydia pneumoniae. In conclusion, the studied lignans act as immunomodulatory agents by altering the cytokine secretion, but do not interfere with dendritic cell maturation. And the observed effects may be associated with the ability of the lignans to alter cellular redox status.

Topics: B7-2 Antigen; Chlamydophila pneumoniae; Coculture Techniques; Cyclooctanes; Dendritic Cells; Gene Expression; Glutathione; HLA-DR Antigens; Humans; Immunologic Factors; Interleukin-10; Interleukin-12; Interleukin-6; Lignans; Lipopolysaccharides; Lymphocyte Activation; Oxidation-Reduction; Polycyclic Compounds; Primary Cell Culture; Reactive Oxygen Species; Schisandra; T-Lymphocytes; THP-1 Cells

Overexpression of P-gp is the main cause of multidrug resistance (MDR) and chemotherapeutic failure in leukemia. In this study, the multidrug resistance reverse effect of Schizandrol A (SchA) was demonstrated with P-gp overexpressed drug-resistant K562/A02 cells. SchA had almost no cytotoxic activity, the EC50 value reversed to DOX was in the nanomole range of (707 ± 29nM) and had a high selectivity index (> 113) to normal cells. DOX accumulation and Rh123 efflux tests demonstrated that the MDR reversal activity of SchA was induced by inhibiting P-gp function. Western blotting assay showed that SchA down-regulated the expression of P-gp by inhibiting the PI3K / Akt signaling pathway, which was also a key factor in reversal activity. Therefore, SchA may be a potential candidate for natural MDR reversal agents.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Death; Cyclooctanes; Doxorubicin; Drug Resistance, Neoplasm; Humans; Intracellular Space; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lignans; Phosphorylation; Polycyclic Compounds; Proto-Oncogene Proteins c-akt; Rhodamine 123

Schizandrin is a major bioactive constituent of Schisandra chinensis (Turcz.) Baill with antioxidant and anti-inflammatory properties. The objective of this study was to explore the potential effects of schizandrin on a cell model of myocarditis. The H9c2 cells were treated with schizandrin alone or in combination with lipopolysaccharide (LPS), after which, cell survival, migration, and the release of inflammatory cytokines were assessed. Moreover, downstream effectors and signaling pathways were studied to reveal the possible underlying mechanism. As a result, LPS stimulation induced significant cell damage as cell viability was repressed and the apoptosis was induced. In the meantime, LPS promoted the release of proinflammatory cytokines including interleukin 1β (IL-1β), IL-8, IL-6, and tumor necrosis factor (TNF-α) while repressing the release of the anti-inflammatory cytokine IL-10. Schizandrin could promote H9c2 cell migration and long-term treatment (7 days) enhanced cell viability. More interestingly, pretreatment with schizandrin attenuated LPS-induced cell loss and inflammatory response. Besides this, Smad3 was a downstream effector of schizandrin. The beneficial effects of schizandrin on the H9c2 cells were attenuated when Smad3 was overexpressed. Moreover, the silencing of Smad3 deactivated c-Jun N-terminal kinase (JNK) and nuclear factor κB (NF-κB) pathways. This study preliminarily demonstrated that schizandrin prevented LPS-induced injury in the H9c2 cells and promoted the recovery of myocardial tissues by enhancing cell viability and migration. Schizandrin conferred its beneficial effects possibly by downregulating Smad3 and inhibiting the activation of JNK and NF-κB pathways.

Topics: Apoptosis; Cell Survival; Cyclooctanes; Cytokines; Down-Regulation; Humans; Lignans; Lipopolysaccharides; MAP Kinase Kinase 4; Myoblasts, Cardiac; NF-kappa B; Polycyclic Compounds; Schisandra; Signal Transduction; Smad3 Protein

Schisandra chinensis fructus (SCF) is widely used traditional Chinese medicine, which possesses hepato-protective potential. Schisandrin (SD), schisantherin (ST), and γ-schizandrin (SZ) are the major bioactive lignans. The main problem associated with the major bioactive lignans oral administration is low oral bioavailability due to the lignans' poor aqueous solubility and taste. The aim of the present research work was to develop liposome (SCL) encapsulated β-cyclodextrin (β-CD) inclusion complex loaded with SCF extract (SCF-E). The SD, ST, and SZ were selected as effective candidates to perform comparisons of liver targeting among the solution (SES), β-cyclodextrin inclusion compound (SCF-E-β-CD), liposome (SEL), and SCL of SCF-E to characterize the pharmacokinetic behaviors and liver targeting in rats. The β-CD inclusion complex (SCF-E-β-CD) was used to improve the solubility. The concentrations were determined using high-performance liquid chromatography (HPLC) and analyzed by DAS3.0. The pharmacokinetic results indicate that the plasma concentration-time courses were fitted well to the one-compartment model with the first weighing factor. The half-life period (t

Topics: Administration, Oral; Animals; beta-Cyclodextrins; Biological Availability; Chromatography, High Pressure Liquid; Cyclooctanes; Drug Compounding; Lignans; Liposomes; Liver; Particle Size; Plant Extracts; Polycyclic Compounds; Rats, Wistar; Schisandra

Traditional Chinese Medicines (TCMs) have been widely used in orient countries for thousands of years, while their inconsistent quality and therapy issues have become increasingly serious as a result of the absence of effective methods for quality control. Therefore, it is necessary to develop a novel and specific evaluation system for TCMs' quality involved with not only composition but also bioactivity. In this study, we used Schisandra chinensis (Turcz.) Baill as an example and developed a novel integrated approach involved with various chemical analysis and data processing methods to explore its quality marker (Q-marker) underlying its anti-depressive effects. First, six bioactive lignans were identified and semi-quantified in rat brain samples via high resolution mass spectrometry. Then, the bioinformation analysis showed that all the six bioactive components could modulate various diseases relative to noradrenergic, dopaminergic and serotonergic pathways. Thus, the monoaminergic metabolites contained in these three pathways were selected to screen potential biomarkers of depression treated by S. chinensis based on target metabolomics using a rapid HPLC-MS/MS method. Finally, the correlation analysis between the six components and potential biomarkers was employed to uncover the Q-markers of S. chinensis. It is suggested that schisandrol A, schisandrin A, schisandrin C and gomisin N could be determined as Q-markers for S. chinensis. Thus, the integrated approach describing here for discovering Q-markers was expected to offer an alternative quality assessment strategy of herbal medicines for the first time.

Topics: Animals; Biomarkers; Chromatography, High Pressure Liquid; Cyclooctanes; Drugs, Chinese Herbal; Gas Chromatography-Mass Spectrometry; Lignans; Medicine, Chinese Traditional; Plants, Medicinal; Polycyclic Compounds; Quality Control; Rats; Schisandra; Tandem Mass Spectrometry

1. Green tea is commonly used worldwide due to its potential positive health benefits. We have examined the effects of epigallocatechin gallate (EGCG), the most abundant catechin in green tea, on the pharmacokinetics of deoxyschizandrin (DSD) and schizandrin (SD), which are the representative lignans in popular traditional Chinese medicines Fructus schisandrae, in rats. 2. The effects on the transport in Caco-2 cells and metabolism in human liver microsomes (HLMs) of DSD and SD by EGCG were determined to analyze their interactions thoroughly. 3. In pharmacokinetic studies, rats were divided into four groups. Each group was orally treated with DSD alone (Group 1), DSD combined with EGCG (Group 2), SD alone (Group 3) and SD combined with EGCG (Group 4). The pharmacokinetic parameters of DSD and SD in rats were determined by UPLC-MS/MS. 4. The in vivo results indicated that EGCG had no significant influence on the pharmacokinetic behaviors of DSD or SD in rats, which were in accordance with the in vitro transport and metabolism studies. However, there were marked differences between male and female rats among C

Topics: Animals; Caco-2 Cells; Catechin; Cyclooctanes; Female; Humans; Lignans; Male; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Tea

Topics: Animals; Benzaldehydes; Benzofurans; Catechols; Chromatography, Liquid; Cyclooctanes; Drug Stability; Drugs, Chinese Herbal; Flavonoids; Lignans; Limit of Detection; Linear Models; Male; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Tandem Mass Spectrometry

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Cerebral Cortex; Chromatography, Liquid; Cognitive Dysfunction; Cyclooctanes; Female; Hippocampus; Lignans; Male; Maze Learning; Memory Disorders; Mice, Inbred C57BL; Mice, Transgenic; Neurotransmitter Agents; Nootropic Agents; Polycyclic Compounds; Presenilin-1; Tandem Mass Spectrometry

Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years and has accumulated considerable knowledge concerning the in vivo efficacy of targeting complicated diseases. TCM formulae are a mixture of hundreds of chemical components with multiple potential targets, essentially acting as a combination therapy of multi-component drugs. However, the obscure substances and the unclear molecular mechanisms are obstacles to their further development and internationalization. Therefore, it is necessary to develop new modern drugs based on the combination of effective components in TCM with exact clinical efficacy. In present study, we aimed to detect optimal ratio of the combination of effective components based on Sheng-Mai-San for myocardial ischemia.. On the basis of preliminary studies and references of relevant literature about Sheng-Mai-San for myocardial ischemia, we chose three representative components (ginsenoside Rb1 (G), ruscogenin (R) and schisandrin (S)) for the optimization design studies. First, the proper proportion of the combination was explored in different myocardial ischemia mice induced by isoproterenol and pituitrin based on orthogonal design. Then, the different proportion combinations were further optimized through uniform design in a multi-model and multi-index mode. Finally, the protective effect of combination was verified in three models of myocardial ischemia injured by ischemia/reperfusion, chronic intermittent hypoxia and acute infarction.. The optimized combination GRS (G: 6 mg/kg, R: 0.75 mg/kg, S: 6 mg/kg) obtained by experimental screening exhibited a significant protective effect on myocardial ischemia injury, as evidenced by decreased myocardium infarct size, ameliorated histological features, decreased myocardial myeloperoxidase (MPO) and malondiadehyde (MDA), calcium overload, and decreased serum lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), cardiac troponin I (cTn-I) activity. In addition, the interactions of three components in combination GRS were also investigated. The combination, compared to G, R and S, could significantly reduce the concentration of serum CK-MB and cTn-I, and decrease myocardial infarct size, which demonstrated the advantages of this combination for myocardial ischemia.. Our results demonstrated that the optimized combination GRS could exert significant cardioprotection against myocardial ischemia injury with similar effect compared to Sheng Mai preparations, which might provide some pharmacological evidences for further development of new modern Chinese drug for cardiovascular diseases basing on traditional Chinese formula with affirmative therapeutic effect.

Topics: Animals; Creatine Kinase, MB Form; Cyclooctanes; Disease Models, Animal; Drug Combinations; Drugs, Chinese Herbal; Ginsenosides; Heart; Isoproterenol; L-Lactate Dehydrogenase; Lignans; Medicine, Chinese Traditional; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Pituitary Hormones, Posterior; Polycyclic Compounds; Spirostans; Troponin I

Topics: Antineoplastic Agents; Apoptosis; Binding Sites; Cell Cycle Checkpoints; Cell Line, Tumor; Cyclooctanes; Drug Screening Assays, Antitumor; G2 Phase; Humans; Inhibitory Concentration 50; Lignans; Molecular Docking Simulation; Polycyclic Compounds; Structure-Activity Relationship

Shengmai San (SMS), a Chinese classic herbal formula, has been widely used for the treatment of Qi-Yin deficiency syndrome in Asia. Modern pharmacological studies have shown that SMS improves the cognitive function. However, the quality markers (Q-markers) for SMS still need further research.. Using chinmedocmics strategy to systematically evaluate the efficacy of SMS in the treatment of APPswe/PS1dE9 (APP/PS1) transgenic model of Alzheimer's disease (AD) and to discover the efficacy-related Q-markers.. The effect of SMS on APP/PS1 mice was evaluated by behavioral test, immunohistochemistry and urine metabolic profile, and the urine marker metabolites associated with SMS treatment of AD were characterized using metabolomics method. In the premise of efficacy, Serum Pharmacochemistry of Traditional Chinese Medicine was applied to investigate the in vivo constituents of SMS. A correlation analysis between marker metabolites of therapeutic effects and serum constituents was completed by chinmedomics approach.. SMS had a therapeutic effect on APP/PS1 mice, and 34 potential urine biomarkers were reversed by SMS treatment. A total of 17 in vivo constituents were detected, including 14 prototype components and 3 metabolites. The correlation analysis showed that eight constituents were extremely correlated with protective effects of SMS in AD, and considered as potential Q-markers of SMS, including schisandrin, isoschisandrin, angeloylgomisin Q, gomisin D, angeloylgomisin H, gomisin M2, ginsenoside F1, 20(R)-ginsenoside Rg3.. This study has demonstrated that chinmedomics is novel strategy for discovering the potential effective constituents from herbal formula, which are recognized as Q-markers.

Topics: Alzheimer Disease; Animals; Biomarkers, Pharmacological; Cyclooctanes; Dioxoles; Disease Models, Animal; Drug Combinations; Drugs, Chinese Herbal; Ginsenosides; Lignans; Male; Medicine, Chinese Traditional; Metabolomics; Mice, Transgenic; Neuroprotective Agents; Polycyclic Compounds

Schisandrin, derived from the Chinese medicinal herb Schisandra chinensis, has been found to confer protective effects on circulation systems. But the underlying molecular mechanisms remain unclear. The aim of this study was to investigate the effects of a high level of glucose on RhoA and eNOS activity in human umbilical vein endothelial cells(HUVECs) and how Schisandrin plays a role in mediating these effects. To find the optimal treatment time, HUVECs were cultured at a high glucose concentration (30 mM) for different lengths of time (0, 12, 24, and 48 h). Subsequently, the cells were randomized into five groups: a normal group, a high glucose group, and three high glucose groups that were given different doses (5, 10, and 20 μM) of Schisandrin. The cells were pretreated with Schisandrin for 24 h before stimulation with high glucose. The morphology of HUVECs in the various groups was assessed under a light microscope. Immunocytochemical staining was used to detect the level of p-MYPT1 expression. The levels of RhoA activity were determined using the RhoA Activation Assay Biochem Kit. The levels of eNOS activity were examined using a nitrate reduction test. The results showed that in the high glucose group, the activity of RhoA was increased and the activity of eNOS was reduced, thus decreasing the secretion of NO. However, after pretreatment with Schisandrin (10, 20 μM), the activity of RhoA was inhibited and the activity of eNOS increased, which led to an increase in NO production compared with the high glucose group. There was no evident difference between the 5 μM Schisandrin group and the high glucose group. Taken together, these findings indicate that Schisandrin can improve the function of endothelial cells by lowering the activity of RhoA/Rho kinase and raising both the activity of eNOS and the production of NO.

Topics: Cyclooctanes; Glucose; Human Umbilical Vein Endothelial Cells; Humans; Lignans; Nitric Oxide Synthase Type III; Polycyclic Compounds; rhoA GTP-Binding Protein

Topics: Administration, Oral; Adult; Chromatography, High Pressure Liquid; Cinnamates; Cyclooctanes; Drugs, Chinese Herbal; Ephedrine; Glucosides; Humans; Lignans; Linear Models; Male; Middle Aged; Monoterpenes; Polycyclic Compounds; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry; Young Adult

The double qualitative principle is a new composite qualitative method based on retention time and the characteristic peaks of the absorption spectra. Using a self-designed and assembled diode array detector (DAD), a high performance liquid chromatography (HPLC) system was constructed. The illegal additive auramine O in six kinds of herbal slices and the active ingredient schisandrin in Jujube kernel Tianma capsules were separated and qualitative analyzed using the HPLC-DAD system. The results showed that there were similar peaks in the chromatograms of pollen typhae and Jujube kernel Tianma capsules when comparing the target analytes. However, the probabilities of the targets were excluded by comparing the absorption spectra. The application results indicated that, based on the double qualitative principle of retention time/absorption spectrum, the interference of impurities in the samples could be well eliminated and the false positives could be avoided. This provides a reference method for the study of traditional Chinese medicine components.

Topics: Chromatography, High Pressure Liquid; Cyclooctanes; Drugs, Chinese Herbal; Lignans; Polycyclic Compounds

Schisandra chinensis, a traditional Chinese medicine (TCM), has been used to treat sleep disorders. Zebrafish sleep/wake behavioral profiling provides a high-throughput platform to screen chemicals, but has never been used to study extracts and components from TCM. In the present study, the ethanol extract of Schisandra chinensis and its two main lignin components, schisandrin and schisandrin B, were studied in zebrafish. We found that the ethanol extract had bidirectional improvement in rest and activity in zebrafish. Schisandrin and schisandrin B were both sedative and active components. We predicted that schisandrin was related to serotonin pathway and the enthanol extract of Schisandra chinensis was related to seoronin and domapine pathways using a database of zebrafish behaviors. These predictions were confirmed in experiments using Caenorhabditis elegans. In conclusion, zebrafish behavior profiling could be used as a high-throughput platform to screen neuroactive effects and predict molecular pathways of extracts and components from TCM.

Topics: Animals; Behavior, Animal; Caenorhabditis elegans; Central Nervous System Agents; Cyclooctanes; Drugs, Chinese Herbal; Lignans; Plant Extracts; Polycyclic Compounds; Schisandra; Zebrafish

To study the anti-inflammatory properties of OJ.. Ojayeonjonghwan (OJ) is a traditional Korean prescription, which has been widely used for the treatment of prostatitis. However, no scientific study has been performed of the anti-inflammatory effects of OJ.. Peritoneal macrophages were isolated 3-4 days after injecting a C57BL/6J mouse with thioglycollate. They were then treated with OJ water extract (0.01, 0.1, and 1 mg/mL) for 1 h and stimulated with lipopolysaccharide (LPS) for different times. Nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and proinflammatory cytokine levels were determined by NO assay, Western blotting, RT-PCR and ELISA.. OJ reduces inflammatory response, and this probably explains its positive impact on the prostatitis associated inflammation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Cyclooctanes; Cyclooxygenase 2; Cytokines; Dioxoles; Ethnopharmacology; Gene Expression Regulation; Lignans; Lipopolysaccharides; Macrophage Activation; Macrophages, Peritoneal; Male; Medicine, Korean Traditional; Mice, Inbred C57BL; Nitric Oxide; Nitric Oxide Synthase Type II; Plant Extracts; Polycyclic Compounds; Prostatitis; Thioglycolates

Topics: Chromatography, High Pressure Liquid; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Humans; Lignans; Polycyclic Compounds; Reproducibility of Results; Tandem Mass Spectrometry

The current study aimed to prove the antidepressant-like effects and the probable mechanisms of Schisandrin on depression, which induced by chronic unpredictable mild stress (CUMS) in mice. Four weeks of CUMS exposure resulted in depressive-like behavior, as indicated by the significant decrease in sucrose consumption and increase the immobility time in the forced swim test, but without any influence on the locomotor activity. Further, there were significant downregulations of GDNF/ERK1/2/ROS and PI3K/AKT/NOX signaling pathways in the hippocampus and prefrontal cortex in depressed mice. Treatment of mice with Schisandrin (30mg/kg) and Fluoxetine (10mg/kg) significantly ameliorated all the behavioral and biochemical changes induced by CUMS. These results suggest that Schisandrin produces an antidepressant-like effect in CUMS-induced mice, which possibly mediated, at least in part, by rectifying the signaling pathways of GDNF/ERK1/2/ROS and PI3K/AKT/NOX.

Topics: Animals; Antidepressive Agents; Cyclooctanes; Depression; Glial Cell Line-Derived Neurotrophic Factor; Hippocampus; Lignans; Male; MAP Kinase Signaling System; Mice; NADPH Oxidases; Phosphatidylinositol 3-Kinases; Polycyclic Compounds; Prefrontal Cortex; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Stress, Psychological; Swimming

Schisandra chinensis (SC) and its main constituent, schizandrin (SCH) exhibit anti-inflammatory and anti-allergic activities. Allergic and inflammatory reactions are aggravated via caspase-1 signaling pathway. However, the regulatory effects of SC and SCH on caspase-1 activation have not been clarified yet. In this study, we aimed to clarify the anti-allergic effects of SC and SCH using an ovalbumin (OVA)-sensitized mice and anti-CD3 and anti-CD28 antibodies-stimulated splenocytes. SC or SCH significantly inhibited the levels of immunoglobulin (Ig)E, IgG1, or interleukin (IL)-4 in serum of OVA-sensitized mice. SC or SCH significantly inhibited the levels of IL-6, tumor necrosis factor (TNF)-[Formula: see text], and IL-1[Formula: see text] in spleen of the OVA-sensitized mice. SC or SCH significantly suppressed the expression of caspase-1 and receptor-interacting protein (RIP)-2 in spleen of the OVA-sensitized mice. In activated splenocytes, SC or SCH significantly decreased the expression of caspase-1 and RIP-2 as well as the production of IL-6 and TNF-[Formula: see text]. We suggest that SC and SCH exert an anti-allergic effect by down-regulating caspase-1 signaling.

Topics: Animals; Caspase 1; Cyclooctanes; Down-Regulation; Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Interleukin-1beta; Interleukin-4; Interleukin-6; Lignans; Mice; Ovalbumin; Plant Extracts; Polycyclic Compounds; Receptor-Interacting Protein Serine-Threonine Kinase 2; Receptor-Interacting Protein Serine-Threonine Kinases; Schisandra; Spleen; Tumor Necrosis Factor-alpha

Topics: Animals; Chromatography, High Pressure Liquid; Cyclooctanes; Drugs, Chinese Herbal; Emodin; Female; Flavanones; Flavonoids; Glucosides; Lignans; Limit of Detection; Linear Models; Male; Monoterpenes; Polycyclic Compounds; Rats; Rats, Wistar; Reproducibility of Results; Tandem Mass Spectrometry

This study was performed to use UHPLC-QTOF/MSE technology to rapidly search and identify variations of chemical ingredients between Fructus Schisandrae Chinensis and its processed products. The present study provides a basis for the study of Chinese herbal medicine processing with a focus on the impact of processing on chemical components. Using a time-dependent data scan mode (MSE) couple with metabolomics technology, we acquired accurate data and identified the potential chemical markers. A total of 12 chemical markers were identified in the crude, \ vinegar-processed and wine-processed Schisandra chinensis fruit; The results showed that the levels of 6-O-benzoylgomisin O, schisantherin B, schisantherin C, schisantherin D and neokadsuranic acid are the highest in crude Schisandra chinensis fruit; thelevels of schizandrin A, schizandrin B, schizandrin C, gomisin D and gomisin T are the highest in wine-processed Schisandra chinensis fruit; the levels of schisantherin A and schisandrin are the highest in vinegar-processed Schisandra chinensis fruit. There were significant changes of chemical components between Fructus Schisandrae Chinensis and their processed products, and these findings may offer a reasonable explanation for variation of efficacy and clinical applications in the processed products of Fructus Schisandrae Chinensis.

Topics: Chromatography, High Pressure Liquid; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Fruit; Lignans; Metabolomics; Polycyclic Compounds; Schisandra

UHPLC-QTOF/MS technique was used to study the differences of lignans and their metabolites derived from Schisandra chinensis and vinegar Schisandra chinensis in rat plasma, bile, urine and faeces by the data processing techniques such as the dynamic background subtract(DBS), mass defect filtering(MDF) and enhance peak list (EPL) in analysis. In order to enhance accuracy for Schisandra chinensis hepatoprotective effect, we established rat acute alcoholic liver injury model in this experiment, and studied the prototype components and metabolisms of Schisandra lignans in vivo under pathological condition. The main ingredients of alcohol extract are lignans, including deoxyschizandrin, schisandrin B, schizandrin C, schizandrol, schizandrol B,schisantherin, schisantherin B, schisanhenol, gomisin G, gomisin J. The metabolic transformation of lignans in rats was mainly induced by methylation, hydroxyl, oxidation, and so on. Finally, we identified 6 kinds of prototype components and their 20 potential metabolites in Schisandra chinensis group and vinegar Schisandra chinensis group.

Topics: Acetic Acid; Animals; Bile; Chromatography, High Pressure Liquid; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Feces; Lignans; Liver Diseases, Alcoholic; Plasma; Polycyclic Compounds; Rats; Schisandra; Urine

GRS is a drug combination of three active components including ginsenoside Rb1, ruscogenin and schisandrin. It derived from the well-known TCM formula ShengMai preparations, a widely used traditional Chinese medicine for the treatment of cardiovascular diseases in clinic. The present study explores the cardioprotective effects of GRS on myocardial ischemia/reperfusion (MI/R) injury compared with ShengMai preparations and investigates the underlying mechanisms. GRS treatment significantly attenuated MI/R injury and exhibited similar efficacy as Shengmai preparations, as evidenced by decreased myocardium infarct size, ameliorated histological features, the decrease of LDH production and improved cardiac function, and also produced a significant decrease of apoptotic index. Mechanistically, GRS alleviated myocardial apoptosis by inhibiting the mitochondrial mediated apoptosis pathway as reflected by inhibition of caspase-3 activity, normalization of Bcl-2/Bax levels and improved mitochondrial function. Moreover, GRS prevented cardiomyocytes mitochondrial fission and upregulated AMPKα phosphorylation. Interestingly, AMPK activation prevented hypoxia and reoxygenation induced mitochondrial fission in cardiomyocytes and GRS actions were significantly attenuated by knockdown of AMPKα. Collectively, these data show that GRS is effective in mitigating MI/R injury by suppressing mitochondrial mediated apoptosis and modulating AMPK activation-mediated mitochondrial fission, thereby providing a rationale for future clinical applications and potential therapeutic strategy for MI/R injury.

Topics: AMP-Activated Protein Kinases; Animals; Apoptosis; Cardiotonic Agents; Cyclooctanes; Drug Combinations; Drug Therapy, Combination; Drugs, Chinese Herbal; Dynamins; Ginsenosides; Lignans; Male; Mice, Inbred ICR; Mitochondrial Dynamics; Myocardial Reperfusion Injury; Polycyclic Compounds; Spirostans

Schizandrin (SCH) has been reported to prevent or reduce learning and memory defects. However, it is not known whether SCH ameliorates cognitive impairments induced by oestrogen deficiency. In the present study, we investigated the effect of SCH on memory in ovariectomized (OVX) and non-OVX rats.. A passive avoidance test was used to evaluate the effect of SCH on memory. Field EPSPs were recorded in hippocampal slices using an electrophysiological method. In OVX rats, biochemical parameters in the bilateral hippocampus were measured; these included superoxide dismutase (SOD), malondialdehyde (MDA) and AChE. Also, the number of NADPH-diaphorase (NADPH-d) positive neurons was counted by NADPH-d histochemistry staining technique.. Oral SCH improved the memory and facilitated the induction of long-term potentiation in non-OVX and OVX rats; this effect was more obvious in OVX rats. Similarly, SCH perfusion enhanced synaptic transmission in hippocampal slices from both non-OVX and OVX rats. However, SCH perfusion reduced the ratio of paired-pulse facilitation only in OVX but not in non-OVX rats. In addition, SCH decreased AChE activity and MDA level and increased SOD activity and the number of NADPH-d-positive neurons in OVX rats.. SCH improves memory in OVX rats and its potential mechanisms may include a reduction in the loss of hippocampal NADPH-d positive neurons, an increase of antioxidant properties and a potentiation of synaptic transmission that possibly involves to enhance cholinergic function. Overall, our findings indicate that SCH has potential as a therapeutic strategy for the cognitive dysfunctions associated with the menopause.

Topics: Acetylcholinesterase; Animals; Antioxidants; Avoidance Learning; Cell Count; Cyclooctanes; Excitatory Postsynaptic Potentials; Female; GPI-Linked Proteins; Hippocampus; Lignans; Long-Term Potentiation; Malondialdehyde; Memory Disorders; Ovariectomy; Polycyclic Compounds; Rats; Superoxide Dismutase; Synaptic Transmission

The transforming growth factor (TGF)-β1 plays a crucial role in the induction of the epithelial-to-mesenchymal transition (EMT) in hepatocytes, which contributes to the pathogenesis of liver fibrosis. The inhibition of the TGF-β1 cascade suppresses EMT and the resultant fibrosis. Schizandrin (Sch) has various therapeutic effects on a range of medical conditions such as anti-asthmatic, anti-cancer, and anti-inflammatory effects. However, the effect of Sch on TGF-β1-stimulated hepatic fibrosis and EMT is still unknown. In the present investigation, we evaluated the anti-fibrotic and anti-EMT properties of Sch and its underlying mechanisms in murine hepatocyte AML12 cells. Overall, we found that Sch inhibited the pro-fibrotic activity of TGF-β1 in AML12 cells; thus, it suppressed the accumulation of ECM proteins. Also, Sch inhibited the EMT as assessed by reduced expression of vimentin and fibronectin, and increased E-cadherin and ZO-1 in TGF-β1 induced AML12 cells. Sch reduced TGF-β1-mediated phosphorylation of Smad2/3 and Smad3/4 DNA binding activity. On the other hand, Sch reduced TGF-β1-induced ERK1/2 and PI3K/Akt phosphorylation in the non-Smad pathway. In conclusion, Sch can antagonize TGF-β1-mediated fibrosis and EMT in AML12 cells. Sch may possess potential as an anti-fibrotic molecule in the treatment of liver fibrosis.

Topics: Animals; Cell Line; Cyclooctanes; Epithelial-Mesenchymal Transition; Fibrosis; Lignans; Liver Diseases; Mice; Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases; Polycyclic Compounds; RNA, Small Interfering; Smad2 Protein; Smad3 Protein; Smad4 Protein; Transforming Growth Factor beta1

To investigate the inhibitory effects of emodin, baicalin, etc. on the hefA gene of multidrug resistance (MDR) in Helicobacter pylori (H. pylori).. The double dilution method was used to screen MDR H. pylori strains and determine the minimum inhibitory concentrations (MICs) of emodin, baicalin, schizandrin, berberine, clarithromycin, metronidazole, tetracycline, amoxicillin and levofloxacin against H. pylori strains. After the screened MDR stains were treated with emodin, baicalin, schizandrin or berberine at a 1/2 MIC concentration for 48 h, changes in MICs of amoxicillin, tetracycline, levofloxacin, metronidazole and clarithromycin were determined. MDR strains with reduced MICs of amoxicillin were selected to detect the hefA mRNA expression by real-time quantitative PCR.. A total of four MDR H. pylori strains were screened. Treatment with emodin, baicalin, schizandrin and berberine significantly decreased the MICs of amoxicillin and tetracycline against some strains, decreased by 1 to 2 times, but did not significantly change the MICs of clarithromycin, levofloxacin, and metronidazole against MDR strains. In the majority of strains with reduced MICs of amoxicillin, hefA mRNA expression was decreased; one-way ANOVA (SPSS 12.0) used for comparative analysis, P < 0.05.. Emodin, baicalin, schizandrin and berberine significantly decreased the MICs of amoxicillin and tetracycline against some H. pylori strains, possibly by mechanisms associated with decreasing hefA mRNA expression.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Berberine; Cyclooctanes; Drug Resistance, Multiple, Bacterial; Drugs, Chinese Herbal; Emodin; Flavonoids; Gene Expression Regulation, Bacterial; Helicobacter pylori; Lignans; Membrane Transport Proteins; Microbial Sensitivity Tests; Polycyclic Compounds; RNA, Messenger

Three dibenzocyclooctadiene lignans: deoxyschizandrin (1), gomisin A (2) and schizandrin (3) were isolated from biomass extracts of Schisandra chinensis (Turcz.) Baill. shoot-differentiating callus cultures. The mentioned lignans were not isolated earlier from in vitro cultures of this plant species. This is the first report concerning on isolation of dibenzocyclooctadiene lignans from in vitro cultures of Schisandra chinensis.

Topics: Cells, Cultured; Chromatography, Thin Layer; Cyclooctanes; Dioxoles; Lignans; Magnetic Resonance Spectroscopy; Plant Leaves; Plant Shoots; Polycyclic Compounds; Schisandra

Structure-activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine-Diphosphate) UDP-glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 μM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, schisandrin, schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 μM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among schisandrin A, schisandrin, and schisandrin C toward UGT1A1 and UGT1A3: schisandrin A > schisandrin > schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (Ki ) to be 0.7 μM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb-drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9-mediated metabolism. In conclusion, in silico-in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis.

Topics: Animals; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Glucuronosyltransferase; Herb-Drug Interactions; Lignans; Plant Extracts; Polycyclic Compounds; Rats; Schisandra; Structure-Activity Relationship

YiQiFuMai Powder Injection (YQFM) is a re-developed preparation based on the well-known traditional Chinese medicine formula Sheng-mai-san. It has been widely used for the treatment of cardiovascular disease with definite clinical efficacy in China, but its bioactive molecules remain obscure. In this study, an effective method has been employed as a tool for screening active components in YQFM, using human umbilical vein endothelial cells (HUVECs) extraction and liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS). Nine compounds, which could interact with HUVECs, were identified as ginsenosides Rb1, Rc, Rb2, Rd, 20(S)-Rg3, 20(R)-Rg3, Rk1/Rg5 and schisandrin by comparing with reference substances or literature. In vitro assays showed that schisandrin at concentrations of 10-100 μM protected HUVECs from hypoxia/reoxygenation (H/R) injury, increased cell viability, nitric oxide (NO) content and decreased lactate dehydrogenase (LDH) leakage, malonaldehyde (MDA) content and ROS generation. Moreover, schisandrin pretreatment inhibited cell apoptosis, as evidenced by inhibiting activation of caspase-3 and increasing the Bcl-2/Bax ratio. These data indicate that HUVECs biospecific extraction coupled with HPLC-ESI-Q-TOF-MS/MS analysis is a reliable method for screening potential bioactive components from traditional Chinese medicines. Meanwhile, the vascular endothelium protective property of schisandrin might be beneficial for the treatment of cardiovascular disease.

Topics: Apoptosis; Cardiovascular Agents; Cell Hypoxia; Cell Survival; Chromatography, High Pressure Liquid; Cyclooctanes; Dose-Response Relationship, Drug; Drug Combinations; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Ginsenosides; Human Umbilical Vein Endothelial Cells; Humans; L-Lactate Dehydrogenase; Lignans; Malondialdehyde; Nitric Oxide; Polycyclic Compounds; Reactive Oxygen Species; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

SMXZF (a combination of ginsenoside Rb1, ginsenoside Rg1, schizandrin and DT-13) derived from Chinese traditional medicine formula ShengMai preparations) is capable of alleviating cerebral ischemia-reperfusion injury in mice. In this study we used network pharmacology approach to explore the mechanisms of SMXZF in the treatment of cardio-cerebral ischemic diseases.. Based upon the chemical predictors, such as chemical structure, pharmacological information and systems biology functional data analysis, a target-pathway interaction network was constructed to identify potential pathways and targets of SMXZF in the treatment of cardio-cerebral ischemia. Furthermore, the most related pathways were verified in TNF-α-treated human vascular endothelial EA.hy926 cells and H2O2-treated rat PC12 cells.. Three signaling pathways including the NF-κB pathway, oxidative stress pathway and cytokine network pathway were demonstrated to be the main signaling pathways. The results from the gene ontology analysis were in accordance with these signaling pathways. The target proteins were found to be associated with other diseases such as vision, renal and metabolic diseases, although they exerted therapeutic actions on cardio-cerebral ischemic diseases. Furthermore, SMXZF not only dose-dependently inhibited the phosphorylation of NF-κB, p50, p65 and IKKα/β in TNF-α-treated EA.hy926 cells, but also regulated the Nrf2/HO-1 pathway in H2O2-treated PC12 cells.. NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases.

Topics: Animals; Brain Ischemia; Cell Line; Cyclooctanes; Drug Combinations; Drugs, Chinese Herbal; Ginsenosides; Humans; Lignans; Myocardial Ischemia; NF-kappa B; Oxidative Stress; PC12 Cells; Polycyclic Compounds; Protein Interaction Maps; Rats; Saponins; Signal Transduction; Systems Biology; Tumor Necrosis Factor-alpha

Disturbances in DNA methylation are postulated to result in various central nervous system diseases including Alzheimer's disease (AD). The SH-SY5Y neuronal cell line treated with Aβ1-40 (5 μmol/L) protein is considered to be a model of AD. Hence the aim of this study was to examine the influence of Schizandrol A, a plant extract, on DNA methylation in SH-SY5Y cells exposed to Aβ1-40. Aβ1-40 were incubated with varying concentrations of Sehizandrol A to a final concentration of 1 (low), 3 (intermediate) or 9 μg/ml (high). Exposure of SH-SY5Y with Aβ1-40 reduced viability, and altered cellular morphology and mRNA expression of DNA methyltransferase (DNMT3A) and DNMT3B. Treatment with 1 or 3 μg/ml Sehizandrol A resulted in normal cell morphology as well as elevated cell number, enhanced viability, and increased mRNA expression of DNMT3A and DNMT3B compared to saline. However, an increase in Sehizandrol A to 9 μg/ml produced a fall in cell viability, as well as a decrease in mRNA DNMT3A and DNMT3B expression to control levels. Data demonstrated that Schizandrol A at 1 or 3 μg/ml improved cell morphological appearance and viability of Aβ1-40 injured SH-SY5Y cells by an enhanced DNA methylation pathway.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Cell Line; Cell Survival; Cyclooctanes; DNA Methylation; Gene Expression Regulation; Humans; Lignans; Neurons; Peptide Fragments; Polycyclic Compounds; Real-Time Polymerase Chain Reaction; RNA, Messenger

Renal proximal tubular epithelial cells are the main targets of toxic drugs such as cisplatin (CisPt), an alkylating agent indicated for the treatment of solid organ tumors. Current techniques aiming at reducing nephrotoxicity in patients receiving CisPt are still not satisfactory as they can only partially prevent acute kidney injury. New nephroprotective strategies remain to be developed. In the present in vitro study, schizandrin (Schi) and schizandrin B (Schi B), major phytochemicals from Schisandra chinensis (Turcz.) Baill. fruits, were tested on HK-2 cells along four processes that could help alleviate CisPt toxicity. Results indicated that: (i) both Schi and Schi B enhanced cell survival via reducing apoptosis rate; (ii) only Schi showed moderate effects towards modulation of regeneration capacities of healthy cells; (iii) both Schi and Schi B limited extracellular matrix deposition; and (iv) both compounds could help preventing dedifferentiation processes via the β-catenin pathway. Schi and Schi B present promising activities for future development of protective agents against CisPt nephrotoxicity.

Topics: Antineoplastic Agents; Cell Culture Techniques; Cell Cycle; Cell Line; Cell Survival; Cisplatin; Collagen; Cyclooctanes; Epithelial Cells; Fruit; Humans; Kidney Tubules, Proximal; Lignans; Molecular Structure; Polycyclic Compounds; Protective Agents; Schisandra

Ginsenoside Rg1, ginsenoside Rb1 and schizandrin are main bioactive components from Panax ginseng and Schisandra chinensis. They have been found in many prescriptions of Traditional Chinese Medicines (TCM) and proven to be effective for prevention and treatment of cardiovascular disease. It is valuable to investigate their pharmacokinetic and pharmacodynamic behavior and potential synergistic effect for better drug development and clinical application.. Pharmacokinetic and nitric oxide (NO) release pharmacodynamic drug-drug interactions of ginsenoside Rg1, ginsenoside Rb1 and schisandrin were studied after intravenous administration of each compound with the dose of 10 mg/kg and their mixture with the total dose of 10 mg/kg to isoproterenol (ISO)-induced myocardial ischemia rats. Drug concentrations in serum were determined using LC-MS method. Nitrite and nitrate (NOx(-)), the predominant oxidation product of NO in serum was used as an effective marker and quantitated by the method of high-performance liquid chromatography coupled with fluorescence detection (HPLC-FL). The main pharmacokinetic parameters of T(1/2β), MRT(0-∞), Vd, Cl, and AUC, and the main pharmacodynamic parameters of Cmax, Tmax and AUEC were calculated by non-compartment model.. The results indicated ginsenoside Rb1 and (or) schisandrin in mixture could significantly postpone the elimination of ginsenoside Rg1 in rat serum. Co-administration of three compounds markedly increased the systemic exposure level of each compound in vivo. Ginsenoside Rg1 and ginsenoside Rb1 had the effect of inducing real-time NO release in rats concentration dependently. Schisandrin had no effect of inducing real-time NO release in this study. The mixture of ginsenoside Rg1, Rb1 and schisandrin administration exhibited synergistic effect of inducing NO release in ISO treated rats.. The result obtained from this study suggested pharmacokinetic and pharmacodynamic drug-drug interactions between ginsenoside Rg1, Rb1 and schisandrin. The study provided valuable information for drug development and clinical application of TCM.

Topics: Administration, Intravenous; Animals; Area Under Curve; Chromatography, High Pressure Liquid; Cyclooctanes; Drug Interactions; Drug Synergism; Ginsenosides; Half-Life; Lignans; Male; Medicine, Chinese Traditional; Models, Biological; Nitric Oxide; Panax; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Schisandra

Recently, combination therapy with acupuncture and medicine as a practical strategy to treat diseases has gained increasing attention. The present study aimed to investigate whether acupuncture stimulation at ST.36 had a potential impact on the pharmacokinetics and tissue distribution of lignans. An HPLC-ESI/MS analytical method was established and successfully applied to a comparative study of drug concentration in plasma and tissues of three lignans. The parameters area under the plasma concentration-time curve from time zero to the final measurable point and from time zero to infinity, and peak concentration were significantly increased, with a prolonged mean residence time and a corresponding decrease in clearance in comparision with the Schisandra-alone group. Additionally, tissue concentrations of three lignans were improved in the group with acupuncture, especially in liver. The results indicated that acupuncture has a synergistic effect on the pharmacokinetics and tissue distribution of the three lignans, which could postpone their elimination, resulting in a longer blood circulating time in rat plasma and prolonged residence time in target tissues, leading to higher tissue concentration. The findings provide some scientific evidence for the mechanism of the combined use of acupuncture and herbal medicine. Furthermore, we suggest that acupuncture and its combination with herbal medicine should be investigated further as a possible adjuvant therapy in clinical treatment for liver injury.

Topics: Acupuncture Therapy; Administration, Oral; Animals; Chromatography, High Pressure Liquid; Cyclooctanes; Lignans; Linear Models; Plant Extracts; Polycyclic Compounds; Rats; Schisandra; Spectrometry, Mass, Electrospray Ionization; Tissue Distribution

A rapid, sensitive and reliable high-performance liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantification of the five main bioactive components, calycosin, calycosin-7-O-β-d-glucoside, formononetin, astragaloside IV and schisandrin in rat plasma after oral administration of Shenqi Wuwei chewable tablets. Plasma samples were extracted using solid-phase extraction separated on a CEC18 column and detected by MS with an electrospray ionization interface in multiple-reaction monitoring mode. Calibration curves offered linear ranges of two orders of magnitude with r > 0.995. The method had a lower limit of quantitation of 0.1, 0.02, 0.1, 1 and 0.1 ng/mL for calycosin, calycosin-7-O-β-d-glucoside, formononetin, astragaloside IV and schisandrin, respectively. Intra- and inter-day precisions (relative standard deviation) for all analytes ranged from 0.97 to 7.63% and from 3.45 to 10.89%, respectively. This method was successfully applied to the pharmacokinetic study of the five compounds in rats after oral administration of Shenqi Wuwei chewable tablets.

Topics: Administration, Oral; Animals; Chromatography, High Pressure Liquid; Cyclooctanes; Drug Stability; Drugs, Chinese Herbal; Glucosides; Isoflavones; Lignans; Linear Models; Male; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Saponins; Sensitivity and Specificity; Tablets; Tandem Mass Spectrometry; Triterpenes

High-speed counter-current chromatography (HSCCC) was used to high performance separate and prepare lignans from Schisandrae chinensis fructus. The solvent system is composed of n-hexane-ethyl acetate-methanol-water (9 : 1 : 5 : 5) and n-hexane-ethyl acetate-methanol-water (9 : 1 : 9 : 5), speed is at 900 r.min-1, and flow rate is at 2.0 mL.min-1. Five fractions from Schisandrae chinensis fructus extract were separated and prepared with one HSCCC process. They were identified as schisandrin, gomisin J, schisandrol B, schisantherin A and deoxyschizandrin by electrospray ionization-multiple tandem mass spectrometry (ESI-MSn), respectively. Their contents were obtained in 98.74%, 94.32%, 99.53%, 94.23% and 98.68% by ultra high performance liquid chromatography (UPLC), separately. The rapid and simple method can be applied for the preparation of lignans from Schisandrae chinensis fructus.

Topics: Countercurrent Distribution; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Fruit; Lignans; Molecular Structure; Plants, Medicinal; Polycyclic Compounds; Schisandra; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

SMXZF is a combination of Rb1, Rg1, schizandrin, and DT-13 (6:9:5:4) derived from Sheng-mai San, a widely used Chinese traditional medicine for the treatment of cardiovascular and cerebral diseases. The present study explores the inhibitory effects and signaling pathways of SMXZF on autophagy induced by cerebral ischemia-reperfusion injury. Male C57BL/6 mice were subjected to ischemia-reperfusion insult by right middle cerebral artery occlusion (MCAO) for 1 hr with subsequent 24 hr reperfusion. Three doses of SMXZF (4.5, 9, and 18 mg/kg) were administered intraperitoneally (i.p.) after ischemia for 1 hr. An autophagic inhibitor, 3-methyladenine (3-MA; 300 μg/kg), was administered i.p. 20 min before ischemia as a positive drug. We found that SMXZF significantly increased cerebral blood flow and reduced the infarct volume, brain water content, and the neurological deficits in a dose-dependent manner. Similar to the positive control, SMXZF at 18 mg/kg also significantly inhibited autophagosome formation. Immunofluorescence staining and Western blotting demonstrated that SMXZF could significantly decrease the expression levels of beclin1 and microtubule-associated protein 1 light chain 3. SMXZF also remarkably inhibited the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) as well as the expression of c-Jun N-terminal kinase (JNK) and its phosphorylation induced by 24 hr reperfusion. Finally, we demonstrated that the optimal administration time of SMXZF was at the early period of reperfusion. This study reveals that SMXZF displays neuroprotective effect against focal ischemia-reperfusion injury, possibly associated with autophagy inactivation through AMPK/mTOR and JNK pathways.

Topics: Adenine; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Autophagy; Brain; Brain Infarction; Cyclooctanes; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Combinations; Drugs, Chinese Herbal; Ginsenosides; Infarction, Middle Cerebral Artery; Lignans; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Polycyclic Compounds; Renal Circulation; Reperfusion Injury; Saponins; Time Factors; TOR Serine-Threonine Kinases

To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification.. A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide (H2O2)-induced PC12 cells by Western blotting.. Twelve differentially expressed proteins (gene names: NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK14, CREB1, IFNG, APP, and BCL2) were confirmed as the central nodes of the interaction network (45 nodes, 93 edges). The NF-κB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of IKKα, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting.. The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-κB signaling pathway as the key targets and pathways for schisandrin.

Topics: Animals; Cerebrovascular Disorders; Cyclooctanes; Drugs, Chinese Herbal; Gene Regulatory Networks; Humans; Lignans; Molecular Targeted Therapy; PC12 Cells; Polycyclic Compounds; Protein Interaction Maps; Rats; Signal Transduction

To establish a method for determination contents of schizandrin, tanshinone I, cryptotanshinone, tanshinone II (A) and schizandrin B in rongxin pills. The HPLC method was performed on an Agilent C18. The mobile phase was composed of methnol and water wish gradient elution. The flow rate was 1.0 mL x min(-1). The column temperature was 30 degrees C and the detection wavelength wash 240 nm. The linear of schizandrin, tanshinone I, cryptotanshinone, Tanshinone II (A) and schizandrin B were 3.000-48.00 (r = 1.000), 3.985-63.76 (r = 0.999 9), 6.370-101.9 (r = 1.000), 8.690-139.0 (r = 0.999 9), 1.700-27.20 mg x L(-1) (r = 0.999 9), respectively. The average recoveries were 98.44%, 100.3%, 99.29%, 99.07%, 98.42%, and RSDs were 0.61%, 1.1%, 0.52%, 0.72%, 0.97%. The method is convenient, accurate and has good precision. It can be used for determination of the preparation.

Topics: Abietanes; Chromatography, High Pressure Liquid; Cyclooctanes; Drugs, Chinese Herbal; Lignans; Linear Models; Organic Chemicals; Phenanthrenes; Polycyclic Compounds; Quality Control; Reproducibility of Results

Metabonomics is a useful tool for studying mechanisms of drug treatment using systematic metabolite profiles. Ginsenosides Rg1 and Rb1, ophiopogonin D, and schizandrin are the main bioactive components of a traditional Chinese formula (Sheng-Mai San) widely used for the treatment of coronary heart disease. It remains unknown the effect of individual bioactive component and how the multi-components in combination affect the treating acute myocardial infarction (AMI).. Rats were divided into 7 groups and dosed consecutively for 7 days with mono and combined-therapy administrations. Serum samples were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy. Partial least squares discriminate analysis (PLS-DA) was employed to distinguish the metabolic profile of rats in different groups and identify potential biomarkers.. Score plots of PLS-DA exhibited that combined-therapy groups were significantly different from AMI group, whereas no differences were observed for mono-therapy groups. We found that AMI caused comprehensive metabolic changes involving stimulation of glycolysis, suppression of fatty acid oxidation, together with disturbed metabolism of arachidonic acid, linoleate, leukotriene, glycerophospholipid, phosphatidylinositol phosphate, and some amino acids. β-hydroxybutyrate, cholines and glucose were regulated by mono-therapy of schizandrin and ginsenosides respectively. Besides these metabolites, combined-therapy ameliorated more of the AMI-induced metabolic changes including glycerol, and O-acetyl glycoprotein. A remarkable reduction of lactate suggested the therapeutic effect of combined-therapy through improving myocardial energy metabolism.. This study provided novel metabonomic insights on the mechanism of synergistic cardioprotection of combined-therapy with ginsenosides, schizandrin, and ophiopogonin D, and demonstrated the potential of discovering new drugs by combining bioactive components from traditional Chinese formula.

Topics: Animals; Cyclooctanes; Drug Combinations; Drugs, Chinese Herbal; Ginsenosides; Lignans; Magnetic Resonance Spectroscopy; Male; Metabolome; Metabolomics; Myocardial Infarction; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Saponins; Spirostans

This study investigated the effects of combined grape pomace and omija fruit extracts (GO) on diabetes-related metabolic changes in type 2 diabetic db/db mice. The effects of GO were compared with those of a resveratrol and schizandrin mixture (RS), which is a mixture of major components of GO. Mice were fed a normal diet with RS (0.005% resveratrol and 0.02% schizandrin in diet, w/w) or GO (0.3% grape pomace ethanol extract and 0.05% omija fruit ethanol extract in diet, w/w) for seven weeks. RS and GO not only lowered the levels of blood and plasma glucose, HbA1c, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) with a simultaneous decrease in hepatic gluconeogenic enzymes activities and adiposity, but also improved preservation of the pancreatic β-cells. Plasma leptin and resistin levels were lower while the plasma adiponectin level was higher in the RS and GO groups than in the control group. Especially, GO increased hepatic glucokinase activity and gene expression and improved hepatic steatosis by elevating fatty acid oxidation compared to RS. These findings suggest that GO ameliorates hyperglycemia, adiposity and hepatic steatosis in type 2 diabetic mice.

Topics: Adiponectin; Adiposity; Animals; Biomarkers; Blood Glucose; Cyclooctanes; Diabetes Mellitus, Experimental; Fatty Liver; Fruit; Glycated Hemoglobin; Hyperglycemia; Insulin; Leptin; Lignans; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Plant Extracts; Polycyclic Compounds; Resistin; Resveratrol; Schisandra; Stilbenes; Vitis

The fruits of Schisandra chinensis have been recorded as an effective somnificant for the treatment of insomnia in some oriental countries pharmacopoeias. However, the mechanism of sedative and hypnotic effects of this kind of herb is still unclear. In the present study, schizandrin, which is the main component of Schisandra chinensis, was selected as a target compound to investigate possible mechanisms through behavioral pharmacology methods. The results showed that schizandrin possessed dose-dependent (5-45 mg/kg, i.p.) sedative effects on locomotion activity in normal mice, and produced a dose-dependent decrease in sleep latency and an increase in sleep duration in pentobarbital-treated mice; thus, itself did not induce sleep at higher dose which was used in this experiment (45 mg/kg, i.p.). It also can reverse the rodent models of insomnia induced by p-chlorophenylalanine (PCPA) and caffeine, which could exhibit a syne with 5-hydroxytryptophan (5-HTP) as well; therefore, the hypnotic effects of schizandrin were not inhibited by flumazenil (a specific gamma aminobutyric acid (GABA)-A-BZD receptor antagonist). Altogether, these results indicated that schizandrin produces beneficial sedative and hypnotic bioactivity, which might be mediated by the modification of the serotonergic system.

Topics: 5-Hydroxytryptophan; Animals; Caffeine; Cyclooctanes; Fenclonine; Flumazenil; Fruit; GABA Antagonists; Hypnotics and Sedatives; Lignans; Locomotion; Male; Mice; Pentobarbital; Polycyclic Compounds; Sleep

A set of central composite design experiments were designed by using four factors which were ethanol amount, ethanol concentration, refrigeration temperature and refrigeration time. The relation between these factors with the target variables of the retention rate of schizandrol A, the soluble solids content, the removal rate of fructose and the removal rate of glucose were analyzed with Bayesian networks, and ethanol amount and ethanol concentration were found as the critical process parameters. Then a network model was built with 2 inputs and 4 outputs using back propagation artificial neural networks which was optimized by genetic algorithms. The R2 and MSE from the training set were 0.983 8 and 0.001 1. The R2 and MSE from the test set were 0.975 9 and 0.001 8. The results showed that network analysis method could be used for modeling of Schisandrae Chinensis Fructus ethanol precipitation process and identify critical operating parameters.

Topics: Bayes Theorem; Chemical Precipitation; Cold Temperature; Cyclooctanes; Ethanol; Fructose; Fruit; Glucose; Lignans; Neural Networks, Computer; Polycyclic Compounds; Reproducibility of Results; Schisandra; Time Factors

To establish a fingerprint of seeds of Schisandra chinensis (SSC) and develop a method of quantitative analysis of multi-components by single marker (QAMS) for simultaneous determining six lignanoids in SSC.. Eleven batches of SSC were determined by HPLC and a common mode of fingerprint has been established. A method was developed for QAMS to determine schizandrol A, schizandrol B, schisantherin A, deoxyschizandrin, schizandrin B and schizandrin C in SSC. Schizandrol A was selected as internal reference; the relative correction factors (RCF)of other five lignanoids to the internal reference were calculated. The contents of the six lignanoids in eleven batches of SSC were determined by both external standard method and QAMS. The QAMS method was evaluated by comparison of its assay results with that of external standard method.. There were 24 common peaks in fingerprints of eleven batches of SSC, six of them were identified. The similarities of fingerprints of eleven batches of SSC were over 0.980. The established RCF had a good reproducibility. No significant differences were found between the quantitative results of external standard method and QAMS.. The developed method is accurate,feasible, and can be used for the qualitative and quantitative analysis of lignanoids in SSC.

Topics: Chromatography, High Pressure Liquid; Cyclooctanes; Dioxoles; Lignans; Polycyclic Compounds; Reproducibility of Results; Schisandra; Seeds

To separate and identify the chemical constituents from the stem of Schisandra chinensis.. Various chromatographic techniques were used to separate and purify the chemical constituents from 95% ethanol extraction of the stem of Schisandra chinensis. Their structures were elucidated based on the physico-chemical properties and spectral data.. Ten compounds were obtained and elucidated as (+)-deoxyschizandrin (1), γ-schizandrin (2), wuweizisu C (3), gomisin N (4), schizandrin (5), anwuweizic acid (6), (-)-dihydroguaiaretic acid (7), tetradecanoic acid (8), β-sitosterol (9) and daucosterol (10).. Compounds 6-8 are obtained from the stem of Schisandra chinensis for the first time.

Topics: Cyclooctanes; Guaiacol; Lignans; Phytochemicals; Plant Stems; Polycyclic Compounds; Schisandra; Sitosterols

To study the chemical constituents from the supercritical CO2 extraction of Schisandra chinensis.. The compounds were separated and purified by conventional column chromatography and their structures were identified by spectroscopic methods.. Nine compounds were isolated from the supercritical CO2 extraction of Schisandra chinensis, and their structures were identified as chrysophanol(1),schisandrin B(2), β-sitosterol(3), schisandrin C(4),schisandrol A(5), angeloylgomisin H(6), daucosterol(7) 1, 5-dimethyl citrate (8), and shikimic acid (9).. Compounds 1, 8 and 9 are isolated from Schisandra chinensis for the first time,and compound 1 as an anthraquinone is isolated from this genus for the first time.

Topics: Cyclooctanes; Lignans; Phytochemicals; Polycyclic Compounds; Schisandra; Sitosterols

Schisandra chinensis (Turcz.) Baill., a traditional Chinese medicine, has been used for treating insomnia for centuries. This paper was designed to study on the plasma pharmacokinetic for its absorption process, and to compare the pharmacokinetics of its active ingredients in normal and insomnic rats orally administrated with the prescription. Therefore, an efficient, sensitive and selective ultra fast liquid chromatography/tandem mass spectrometry (UFLC-MS/MS) method for the simultaneous determination of six sedative and hypnotic lignans (schisandrin, schisandrol B, schisantherin A, deoxyshisandrin, γ-schisandrin and gomisin N) of Schisandra chinensis (Turcz.) Baill. in rat plasma has been developed and validated. The analysis was performed on a Shim-pack XR-ODS column (75mm×3.0mm, 2.2μm) using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid waterat a flow rate of 0.4ml/min. The detection of the analytes was performed on 4000Q UFLC-MS/MS system with turbo ion spray source in the positive ion and multiple reaction-monitoring mode. The method was validated in plasma samples, which showed good linearity over a wide concentration range (r(2)>0.99), and obtained lower limits of quantification were 10, 1.2, 1.2, 1.2, 1.0 and 1.2ngmL(-1) for the analytes. The intra- and inter-day assay variability was less than 15% for all analytes. The mean extraction recoveries of analytes and IS from rats plasma were all more than 85.0%. The validated method has been successfully applied to comparing pharmacokinetic profiles of analytes in rat plasma. The results indicated that significant difference in pharmacokinetic parameters of the analytes was observed between two groups, while absorptions of these analytes in insomnic group were all significantly higher than those in normal group.

Topics: Animals; Chromatography, High Pressure Liquid; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Lignans; Male; Medicine, Chinese Traditional; Polycyclic Compounds; Random Allocation; Rats; Rats, Sprague-Dawley; Schisandra; Sensitivity and Specificity; Sleep Initiation and Maintenance Disorders; Tandem Mass Spectrometry

Phytochemical investigation of an ethanolic extract of stems of Schisandra neglecta led to the isolation and identification of two new dibenzocyclooctadiene lignans, designated neglschisandrins E (1) and F (2), and thirteen known lignans. All structures and stereochemistries were determined by spectroscopic methods, including 2D-NMR techniques. The isolates were evaluated for in vitro cytotoxic activity. Among them, compounds 2-6 exhibited moderate to weak cytotoxicity against the human colorectal carcinoma HCT-8 cell line with EC₅₀ values of 7.33~19.8 μg/mL. In addition, compounds 2-4 also exhibited marginal cytotoxicity against the human lung carcinoma A549 cell line with EC₅₀ values of 11.8~15.0 μg/mL.

Topics: Cell Death; Cell Line, Tumor; Cyclooctanes; Drug Screening Assays, Antitumor; Humans; Lignans; Magnetic Resonance Spectroscopy; Models, Molecular; Polycyclic Compounds; Schisandra

Recently, the combination of acupuncture and Chinese medicine as a practical strategy to treat diseases is receiving considerable attention worldwide as they are usually found to exhibit intriguing therapeutic effectiveness. The current study aimed to study the adjunct effect of acupuncture on target tissue distribution of schisandra lignans when acupuncture is combined with Schisandra chinensis.. A simple and reliable high performance liquid chromatography-electrospray tandem-mass spectrometry (HPLC-ESI-MS) method for simultaneous analysis of three bioactive lignans (schisandrin, deoxyschisandrin and schisandrin B) in rat tissues was established. Using this analytical method we evaluated whether acupuncture had a synergistic effect on the tissue distribution of schisandra lignans.. Tissue concentrations of the three lignans in the group receiving acupuncture were significantly higher than those in the schisandra only group, suggesting that acupuncture may potently increase tissue concentrations of schisandra lignans. The highest concentrations of the three lignans occurred in the liver compared with other tissues, and tissue concentrations in the heart, spleen, lungs and kidneys were increased by 315%, 203%, 250% and 224%, respectively. In addition, retention times of the lignans in tissues were prolonged for a relative long time.. Our date indicate that the combined use of acupuncture and Schisandra chinensis could produce a synergistic effect which could play a beneficial role on promoting the tissue distribution of lignans. This has supported our initial hypothesis. The HPLC-MS method showed good sensitivity in quantifying the three schisandra lignans in different tissues.

Topics: Acupuncture Therapy; Animals; Chromatography, High Pressure Liquid; Cyclooctanes; Lignans; Polycyclic Compounds; Rats; Spectrometry, Mass, Electrospray Ionization; Substrate Specificity; Tandem Mass Spectrometry; Tissue Distribution

This study aimed to investigate the in vivo behaviors of the main components in traditional Chinese medicine (TCM) fomulae. The plasma pharmacokinetics, tissue distribution and excretion of the main component-schisandrin in rats after oral administration of a classical TCM prescription, shengmaisan (SMS), were studied by a developed and validated UPLC-MS/MS method. The separation of schisandrin was achieved on a UPLC HSS T3 column with a mobile phase consisting of acetonitrile and water at a flow rate of 0.5 mL/min by linear gradient elution. The MS/MS detection was carried out by monitoring the fragmentation of m/z 415.22 → 384.26 for schisandrin on a triple quadrupole mass spectrometer. The result showed that the method was suitable for the quantification of schisandrin in plasma, tissue and excreta samples with satisfactory selectivity, precision, accuracy, sensitivity, linearity and recovery. Pharmacokinetic results showed a rapid absorption phase with the mean Tmax of 0.17 h and a relatively slow elimination proceeding with a half-life (T1/2 ) of 5.24 ± 1.28 h. The tissue distribution showed the maximum concentration distributions of schisandrin after oral administration of SMS were in the order of small intestine > large intestine > lung > liver > kidney > spleen > heart > brain. Only 0.005-0.006% of schisandrin was recovered in feces and was not detected in urine.

Topics: Administration, Oral; Animals; Chromatography, High Pressure Liquid; Cyclooctanes; Drug Combinations; Drugs, Chinese Herbal; Feces; Lignans; Male; Organ Specificity; Polycyclic Compounds; Rats; Rats, Wistar; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry

It is valuable to establish a chemical-pharmacokinetic (PK)-pharmacodynamics (PD) fingerprint of traditional Chinese medicine (TCM) for comprehensively understanding the TCM integrated conception and revealing the material foundation. The chemical, metabolic in vitro, and PK/PD in vivo fingerprints of Schisandra chinensis (SC) alcoholic extract were established and comparatively analyzed using HPLC-UV-MS method, rat liver microsomes in vitro and CCl4 intoxicated rats in vivo. Four known effective lignans, schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin, were detected as the standard references in SC alcoholic extract with high concentration. SC alcoholic extract and four lignans when incubated with rat liver microsomes produced several metabolites in NAPDH-dependent manner. Chemical fingerprint of some components with bioactivities were also identified in PK and PD fingerprints in normal and ALI rats that explained the material foundation of SC alcoholic extract for multiple pharmacological effects. Schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin could be considered as the "PK marker" of SC alcoholic extract or its relevant preparations, while two metabolites of the four lignans, 7, 8-dihydroxy-schizandrin and another one (M(W) 432), could be recognized as drug-metabolism (DM) Marker. This work provides experimental data for the further studies of metabolism or material foundation of SC components.

Topics: Alanine Transaminase; Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Chromatography, High Pressure Liquid; Cyclooctanes; Drugs, Chinese Herbal; Lignans; Male; Microsomes, Liver; Plants, Medicinal; Polycyclic Compounds; Random Allocation; Rats; Rats, Sprague-Dawley; Schisandra; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet

The effects of 15 preparations with general tonic, antioxidant, and antihypoxant activities on exercise performance of laboratory rats were studied in the forced swimming test. The best recovery and improvement of exercise performance was recorded after a single intragastric dose of schizandrin and acyzol. These drugs stimulated an increase in the parameters in control animals by 86 and 72% (exercise performance recovery) and by 33 and 51% (exercise performance improvement).

Topics: Administration, Oral; Animals; Animals, Outbred Strains; Antioxidants; Central Nervous System Stimulants; Cyclooctanes; Imidazoles; Lignans; Organometallic Compounds; Oxidative Stress; Physical Conditioning, Animal; Physical Endurance; Polycyclic Compounds; Rats; Swimming

Shengmaisan (SMS) is a traditional Chinese medicine prescription widely used for the treatment of cardiovascular diseases in Asia. Its lignans are major components responsible for therapeutic action. A rapid and specific UPLC-Q-TOF/MS has been developed and validated for simultaneous quantification of the five main bioactive components, i.e. schisandrin, schisandrol B, schisantherin A, deoxyschisandrin, and schisandrin B, in rat plasma after oral administration of SMS. All calibration curves showed excellent linearity within the test ranges. Validation proved the repeatability of the method was good and recovery was satisfactory. The separation of these compounds was carried out on a Waters ACQUITY HSS T(3) column (2.1 × 100 mm, 1.8 μm) by linear gradient elution using a mobile phase consisting of 0.01% formic acid in water and ACN containing 0.01% formic acid. In this work, plasma pharmacokinetic characteristics of lignans components after oral administration SMS were investigated using UPLC-Q-TOF/MS method. MS was performed on a Waters Micromass high-definition technology with an ESI source. Data were analyzed and estimated by compartmental methods and pharmacokinetic parameters calculated using WinNonlin Professional version 6.1. Results demonstrated that the proposed UPLC-Q-TOF/MS method was successfully applied to pharmacokinetic study of all components in rat plasma after oral administration of the SMS.

Topics: Administration, Oral; Animals; Chromatography, High Pressure Liquid; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Lignans; Male; Polycyclic Compounds; Rats; Rats, Wistar; Spectrometry, Mass, Electrospray Ionization

High glucose (HG) is the underlying factor contributing to long term complication of diabetes mellitus. Reactive oxygen species (ROS) have been postulated as a unifying mechanism for HG-induced complications. NADPH oxidase, producing superoxide anion, is the main source of ROS in diabetic nephropathy. In this study we report the inhibitory effect of schizandrin (Sch), an active ingredient of Fructus schisandrae, on HG-induced murine mesangial cells (MMCs) damage. Sch treatment significantly attenuated HG-induced proliferation and protein synthesis of MMCs in a dose dependent manner. The intracellular reactive oxygen species (ROS) level was also remarkably reduced by Sch as well as the enhanced NADPH oxidase activity, superoxide anion levels, NOX4 and p22phox protein expression, and phosphorylation of p47phox and p67phox. The phosphorylation level of mitogen activated kinase (MAPK) protein, phospho-Erk1/2 and -p38, and Akt was also significantly inhibited by Sch under HG condition. By using specific inhibitors, we found that Sch inhibits HG-induced mesangial cell proliferation and ECM overexpression via NADPH oxidase/PI3K-Akt-MAPK-dependent pathway in MMCs. Taken together; our demonstration of the ability of Sch to inhibit high glucose induced damage of MMCs has clinical implications in treatment of diabetic nephropathy.

Topics: Animals; Cell Line, Transformed; Cell Proliferation; Collagen Type IV; Cyclooctanes; Fibronectins; Glomerular Mesangium; Glucose; Lignans; MAP Kinase Signaling System; Mice; NADPH Oxidases; Phosphorylation; Polycyclic Compounds; Reactive Oxygen Species; Signal Transduction; Transforming Growth Factor beta1

To investigate the pharmacokinetic interaction among three major bioactive compounds of Shengmai formula.. After oral administration of ginsenoside Rg(1), ginsenoside Rb(1) and schisandrin with the same dose(100 mg.kg(-1)) individually or in combination, rat serum samples were extracted, then these three compounds were determined by liquid chromatography-mass spectrometry(LC-MS). The pharmacokinetic parameters of three compounds in single or combination form were calculated by WinNonLinu6.0 using non-compartment model.. Compared with single drug group, the peak concentration of ginsenoside Rg(1) in combined group increased from(0.476 ±0.238) μg.ml(-1) to (1.946 ±1.432) μg.ml(-1), AUC(0-∞) increased from(0.523 ±0.238) μg.h.ml(-1) to (1.908 ±1.319) μg.h.ml(-1), CL decreased from(226311 ± 96819) ml.h(-1).kg(-1) to(90650 ±73684) ml.h(-1).kg(-1) and Vd decreased from(317110 ±154009) ml.kg(-1) to(130967 ±78306) ml.kg(-1). While the pharmacokinetic parameters of ginsenoside Rb(1) and schisandrin showed no significant change.. Combined oral administration of three compounds of Shengmai formula can improve the bioavailability of ginsenoside RgRg(1), however it does not change the pharmacokinetic behavior of ginsenoside RbRg(1) and schisandrin.

Topics: Animals; Biological Availability; Chromatography, Liquid; Cyclooctanes; Drug Synergism; Ginsenosides; Lignans; Male; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

In the present study, we examined the effect of schisandrin (SCH) of Schisandra chinensis on the amyloid-beta(1-42)- (Aβ(1-42)-) induced memory impairment in mice and elucidated the possible antioxidative mechanism. Mice were intracerebroventricular (i.c.v.) injected with the aggregated Aβ(1-42) and then treated with SCH (4, 12, and 36 mg/kg body weight) or donepezil (DPZ), a reference drug (0.65 mg/kg) by intragastric infusion for 14 days. Noncognitive disturbances and cognitive performance were evaluated by locomotor activity test, Y-maze test, and water maze test. Antioxidative enzyme activities including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and levels of malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG) within the cerebral cortex and hippocampus of mice were measured to elucidate the mechanism. Our results showed that SCH significantly improved Aβ(1-42)-induced short-term and spatial reference memory impairments in Y-maze test and water maze test. Furthermore, in the cerebral cortex and hippocampus of mice, SOD and GSH-px activities, GSH level, and GSH/GSSG ratio were increased, and levels of MDA and GSSG were decreased by the treatment of SCH. These results suggest that SCH is a potential cognitive enhancer against Alzheimer's disease through antioxidative action.

Topics: Amyloid beta-Peptides; Animals; Antioxidants; Biological Assay; Cerebral Cortex; Cyclooctanes; Hippocampus; Lignans; Male; Maze Learning; Memory Disorders; Mice; Motor Activity; Peptide Fragments; Polycyclic Compounds; Reaction Time; Schisandra

Thymic stromal lymphopoietin (TSLP) plays an important role in allergic diseases such as asthma and atopic dermatitis. Schizandrin has various effects such as anti-asthmatic, anti-cancer and anti-inflammatory effects. However, the effect of schizandrin on the production of TSLP has not been clarified. Thus, we investigated how schizandrin inhibits the production of TSLP in the human mast cell line HMC-1 cells.. We used enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, luciferase assay, and Western blot analysis to investigate the effects of schizandrin.. Schizandrin inhibited the production and mRNA expression of TSLP in HMC-1 cells. The maximal inhibition rate of TSLP production by schizandrin (10 μM) was 68.62 ± 3.47%. Schizandrin inhibited the translocation and luciferase activity of nuclear factor-κB induced by phorbol myristate acetate plus A23187. In the activated HMC-1 cells, the activation of caspase-1 was increased, whereas the activation of caspase-1 was decreased by pretreatment with schizandrin.. These results suggest that schizandrin can be used to treat inflammatory and atopic diseases through the inhibition of TSLP.

Topics: Blotting, Western; Calcimycin; Caspase 1; Cell Line; Cyclooctanes; Cytokines; Enzyme-Linked Immunosorbent Assay; Humans; Lignans; Luciferases; Mast Cells; Polycyclic Compounds; Reverse Transcriptase Polymerase Chain Reaction; Tetradecanoylphorbol Acetate; Thymic Stromal Lymphopoietin

To model glucocorticoid-induced cognitive impairment and evaluate the neuroprotection by schizandrin (Sch) against dexamethasone (Dex)-induced neurotoxicity in vivo and in vitro.. Cerebral cortical cells from neonatal Sprague-Dawley rats (within 24 hours after birth) were cultured for 9 days, and then treated with Dex (10(-4), 10(-5), 10(-6) or 10(-7) mol/L) for 24 h or pretreated with 10(-4) mol/L Dex for 24 h followed by 10, 20, 40, or 80 μmol/L Sch for 48 h. Cell viability was assessed using the MTT assay. Immunofluorescence and real-time PCR for MAP2 were performed to confirm the effects of Dex on neurite outgrowth. In vivo, kunming mice were randomly divided into six groups: control [(intragastric (i.g.) vehicle for 42 days]; Dex group I (5 mg/kg · d(-1) Dex i.g. treatment for 28 days followed by i.g. vehicle for 14 days); Dex group II (Dex i.g. for 42 days); Dex + Sch (Dex i.g. for 28 days followed by 5, 15, or 45 mg/kg · d(-1) Sch i.g. for 14 days). Learning and memory were assessed by Morris water maze test. Histological examination was used to assess pathology and apoptosis in neurons.. Compared to the Dex groups, Sch increased cell viability in a dose-dependent manner, improved performance in the Morris water maze and ameliorated the morphological changes.. Sch has neuroprotective effects against insults induced by glucocorticoid.

Topics: Animals; Animals, Newborn; Cell Survival; Cells, Cultured; Cerebral Cortex; Cognition Disorders; Cyclooctanes; Dexamethasone; Dose-Response Relationship, Drug; Lignans; Male; Mice; Neuroprotective Agents; Polycyclic Compounds; Random Allocation; Rats; Rats, Sprague-Dawley; Schisandra

Schisandra, a globally distributed plant, has been widely applied to health care products. Here, we investigated the effects of dietary intake of Fructus Schisandrae chinensis (FSC), both aqueous and ethanolic extracts (AqFSC, EtFSC), on serum/hepatic lipid contents in normal diet (ND)- and high-fat/cholesterol/bile salt diet (HFCBD)-fed mice.. Male ICR mice were fed with ND or HFCBD, supplemented with 1 and 4% of AqFSC and EtFSC, respectively, or 0.1% fenofibrate, for 13 days. Lipids were determined according to the manufacture's instructions.. EtFSC, but not AqFSC, significantly elevated hepatic triglyceride (TG) in mice fed with ND. Feeding mice with HFCBD increased serum total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) levels as well as alanine aminotransferase (ALT) activity. Supplementation with AqFSC, EtFSC or fenofibrate significantly reduced hepatic TC and TG levels. However, AqFSC and EtFSC supplementation increased serum HDL and LDL levels in mice fed with HFCBD. Fenofibrate increased serum HDL and reduced serum LDL contents in hypercholesterolemic mice. EtFSC reduced, but fenofibrate elevated, serum ALT activity in both normal and hypercholesterolemic mice. While fenofibrate reduced serum TC, TG, and HDL levels in mice fed with ND, it increased serum HDL and reduced serum LDL and TC levels in mice fed with HFCBD. Hepatomegaly was found in normal and hypercholesterolemic mice fed with diet supplemented with fenofibrate.. Feeding mice with AqFSC and EtFSC ameliorated the HFCBD-induced hepatic steatosis. In addition, EtFSC may offer protection against hepatic injury in hypercholesterolemic mice.

Topics: Animals; Cyclooctanes; Diet; Drugs, Chinese Herbal; Fenofibrate; Fruit; Hypercholesterolemia; Hypolipidemic Agents; Lignans; Lipid Metabolism; Lipids; Liver; Mice; Polycyclic Compounds; Triglycerides

The aim of the study is to establish a new method of quality evaluation and validate its feasibilities by the simultaneous quantitative assay of four lignanoids in Schisandra chinensis. A new quality evaluation method, quantitative analysis of multi-components by single marker (QAMS), was established and validated with Schisandra chinensis. Four main lignanoids, schisandrin, schisantherin A, deoxyschizandrin and gamma-schizandrin, were selected as analytes and schisandrin as internal reference substance to evaluate the quality. Their contents in 13 different batches of samples, collected from different bathes, were determined by both external standard method and QAMS. The method was evaluated by comparison of the quantitative results between external standard method and QAMS. No significant differences were found in the quantitative results of four lignanoids in 13 batches of S. chinensis determined by external standard method and QAMS. QAMS is feasible for determination of four lignanoids simultaneously when some authentic standard substances were unavailable, and the developed method can be used for quality control of S. chinensis.

Topics: Chromatography, High Pressure Liquid; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Fruit; Lignans; Plants, Medicinal; Polycyclic Compounds; Quality Control; Schisandra

Glutamate-induced excitotoxicity has been implicated in a variety of neuronal degenerative disorders. In the present study, we investigated the possible neuroprotective effects of schizandrin against apoptosis of primary cultured rat cortical cells induced by glutamate. Glutamate (10 μM) administered for 24 h decreased the expression of Bcl-2 and Bcl-X(L) protein, whereas increased the expression of Bax, Bak, apoptosis inducing factor (AIF), endonuclease G (Nodo G) and endoplasmic reticulum (ER) stress of caspase-12. Pretreatment with schizandrin (100 μM) before glutamate treatment increased the Bcl-X(L) and Bcl-2 expression and decreased Bax, Bak, AIF, Nodo G and caspase-12 compared with those only treated with glutamate. Furthermore, glutamate-induced phosphorylation of JNK, p38 and ERK mitogen-activated protein kinases (MAPK), and these effects were attenuated by schizandrin (100 μM) treatment. These results suggest that schizandrin possesses the neuroprotective effects. The molecular mechanisms of schizandrin against glutamate-induced apoptosis may involve the regulation of Bcl-2 family proteins expression, and ER stress through blocking the activation of JNK, ERK and p38 MAPK.

Topics: Animals; Apoptosis; bcl-2 Homologous Antagonist-Killer Protein; bcl-2-Associated X Protein; Blotting, Western; Caspase 12; Cells, Cultured; Cerebral Cortex; Cyclooctanes; Fas Ligand Protein; fas Receptor; Glutamic Acid; Lignans; Mitochondria; Mitogen-Activated Protein Kinases; Neuroprotective Agents; Phosphorylation; Polycyclic Compounds; Primary Cell Culture; Signal Transduction; Tumor Suppressor Protein p53

Aggregated beta-amyloid (Aβ) and elevated plasma levels of homocysteine have been implicated as critical factors in the pathogenesis of Alzheimer's disease. The neuroprotective effects and possible mechanism of four structurally similar dibenzocyclooctadiene lignans (namely schisandrin, schisantherin A, schisandrin B and schisandrin C) isolated from the fruit of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) against Aβ₂₅₋₃₅ and homocysteine toxicity in PC12 cells was studied. Exposure of PC12 cells to 0.5 µm Aβ₂₅₋₃₅ caused significant cell death, increased the number of apoptotic cells, elevated reactive oxygen species, increased the levels of the pro-apoptotic protein Bax and caspase-3 activation. All these effects induced by Aβ₂₅₋₃₅ were markedly reversed by schisandrin B and schisandrin C pretreatment, while schisandrin and schisantherin A had no obvious effects. Meanwhile, schisandrin B and schisandrin C reversed homocysteine-induced cytotoxicity. The results indicated that schisandrin B and schisandrin C protected PC12 cells against Aβ toxicity by attenuating ROS production and modulating the apoptotic signal pathway through Bax and caspase-3. Further structure-activity analysis of Schisandra lignans and evaluations of their neuroprotective effects using AD animal models are warranted.

Topics: Amyloid beta-Peptides; Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cyclooctanes; Dioxoles; Homocysteine; Lignans; Neuroprotective Agents; PC12 Cells; Peptide Fragments; Polycyclic Compounds; Rats; Reactive Oxygen Species; Schisandra

Schisandra chinensis, commonly used in Asia for tea material and traditional Chinese medicine, is presumed to enhance mental and intellectual functions. In this study, the effects and signalling mechanisms of a purified compound schisandrin, one of the lignan of Schisandra chinensis, on primary cultured hippocampal neurons were investigated.. Schisandrin treatment enhanced total dendritic length and branching complexity, both of which were significantly suppressed in the presence of specific blockers for calmodulin-dependent kinase II (CaMKII), protein kinase C epsilon (PKCε), and mitogen activated protein kinase kinase (MEK). Moreover, schisandrin induced calcium influx, and phosphorylation of CaMKII, PKCε, and MEK. Inhibition of CAMKII and PKCε attenuated the schisandrin-induced phosphorylation of PKCε and MEK, and the phosphorylation of MEK, respectively. Moreover, schisandrin also stimulated the phosphorylation of cyclic AMP responsive-element binding protein (CREB) at Ser-133, an effect that was blocked by KN93. In addition to its neuritogenic effects, schisandrin increased the numbers of postsynaptic density-95-positive and FM1-43-positive puncta in dendrites and synaptic boutons, respectively.. In hippocampal neurons, schisandrin exhibits neurotrophic properties that are mediated by the CaMKII-PKCε-MEK pathway.

Topics: Animals; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cyclic AMP Response Element-Binding Protein; Cyclic Nucleotide Phosphodiesterases, Type 1; Cyclooctanes; Dendrites; Fruit; Hippocampus; Lignans; Mitogen-Activated Protein Kinase Kinases; Neurogenesis; Phosphorylation; Plant Extracts; Polycyclic Compounds; Post-Synaptic Density; Presynaptic Terminals; Protein Kinase C-epsilon; Rats; Rats, Wistar; Schisandra

Schiglautone A (1), a unique 6/7/9-fused tricyclic carbon backbone triterpenoid, was isolated from the stems of Schisandra glaucescens. Its structure was determined on the basis of spectroscopic analysis and single-crystal X-ray crystallography. A hypothetical biosynthetic pathway of 1 was postulated.

Topics: Crystallography, X-Ray; Cyclooctanes; Lignans; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plant Stems; Polycyclic Compounds; Schisandra; Triterpenes

The ionic liquid-based ultrasonic-assisted extraction (ILUAE) has been successfully applied in extracting four biphenyl cyclooctene lignans from the fruit of Schisandra chinensis Baill. Seventeen different types of ionic liquids with different cations and anions have been investigated. 0.8 M 1-lauryl-3-methylimidazolium bromide ([C12mim]Br) solution was selected as solvent. In addition, the ultrasonic parameters including ultrasonic power, time for ultrasonic treatment and solid-liquid ratio have been optimized by Response Surface Method (RSM). Compared with the conventional solvent extraction, the efficiency of the approach proposed in this work is about 3.5 times as much as that of the conventional solvent extraction method. With the proposed extraction method, the extraction time has been reduced to 30 min, whereas the conventional extraction method requires about 6.0 h. The experimental results presented in this work indicate that the ILUAE is a simple and efficient technique for sample preparation. The proposed method is reproducible.

Topics: Chromatography, High Pressure Liquid; Cyclooctanes; Fruit; Ionic Liquids; Lignans; Plant Extracts; Polycyclic Compounds; Schisandra; Solid Phase Extraction; Time Factors; Ultrasonics

This study examined the effect of schisandrin, one of the major lignans isolated from Schisandra chinensis, on spontaneous contraction in rat colon and its possible mechanisms. Schisandrin produced a concentration-dependent inhibition (EC₅₀=1.66 μM) on the colonic spontaneous contraction. The relaxant effect of schisandrin could be abolished by the neuronal Na+ channel blocker tetrodotoxin (1 μM) but not affected by propranolol (1 μM), phentolamine (1 μM), atropine (1 μM) or nicotine desensitization, suggesting possible involvement of non-adrenergic non-cholinergic (NANC) transmitters released from enteric nerves. N(ω)-nitro-l-arginine methyl ester (100-300 μM), a nitric oxide synthase inhibitor, attenuated the schisandrin response. The role of nitric oxide (NO) was confirmed by an increase in colonic NO production after schisandrin incubation, and the inhibition on the schisandrin responses by soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3-α]-quinoxalin-1-one (1-30 μM). Non-nitrergic NANC components may also be involved in the action of schisandrin, as suggested by the significant inhibition of apamin on the schisandrin-induced responses. Pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt hydrate (100 μM), a selective P2 purinoceptor antagonist, markedly attenuated the responses to schisandrin. In contrast, neither 8-cyclopentyl-1,3-dipropylxanthine, an antagonist for adenosine A₁ receptors, nor chymotrypsin, a serine endopeptidase, affected the responses. All available results have demonstrated that schisandrin produced NANC relaxation on the rat colon, with the involvement of NO and acting via cGMP-dependent pathways. ATP, but not adenosine and VIP, likely plays a role in the non-nitrergic, apamin-sensitive component of the response.

Topics: Adrenergic Antagonists; Animals; Atropine; Benzyl Compounds; Colon, Ascending; Cyclic GMP; Cyclooctanes; Enzyme Inhibitors; Imidazoles; In Vitro Techniques; Lignans; Male; Muscle Contraction; Muscle Relaxation; Nitric Oxide; Phentolamine; Plant Extracts; Polycyclic Compounds; Propranolol; Purinergic Antagonists; Pyridoxal Phosphate; Rats; Rats, Sprague-Dawley; Receptors, Epoprostenol; Schisandra; Tetrodotoxin; Xanthines

Lignans are imporant active ingredients of Schisandra sphenanthera. A micellar electrokinetic chromatography method was developed for the simultaneous determination of eight lignans--schizandrin, schisandrol B, schisantherin A, schisanhenol, anwulignan, deoxyschizandrin, schizandrin B and schizandrin C--in different parts of S. sphenanthera. The key factors for separation and determination were studied and the best analysis conditions were obtained using a background electrolyte of 10 mM phosphate-37.5 mM SDS-35% v/v acetonitrile (pH 8.0) at the separation voltage of 28 kV and detection at 214 nm, whereby the plant samples could be analyzed within 9.0 min. Analysis yielded good reproducibility (RSD between 1.19-2.28%) and good recovery (between 92.2-103.8%). The detection limits (LOD) and limit of quantification (LOQ) were within 0.4-1.2 mg/L and 1.5-4.0 mg/L. This method is promising to improve the quality control of different parts of S. sphenanthera.

Topics: Chromatography, Micellar Electrokinetic Capillary; Cyclooctanes; Dioxoles; Lignans; Polycyclic Compounds

The lipopolysaccharide (LPS) of Porphyromonas gingivalis is thought to induce periodontitis. In this study, we isolated Schisandrin from the dried fruits of Schisandra chinensis and examined the anti-inflammatory effect of Schisandrin in macrophages stimulated with LPS from P. gingivalis. First, Schisandrin inhibited LPS-induced pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. And Schisandrin suppressed the nuclear translocation and activity of NF-κB and phosphorylation of IκBα in LPS-stimulated RAW 264.7 cells. Next, the presence of a selective inhibitor of HO-1 (SnPP) and a siRNA specific for HO-1 inhibited Schisandrin-mediated anti-inflammatory activity. Furthermore, Schisandrin induced HO-1 expression of RAW 264.7 cells through Nrf-2, PI3K/Akt, and ERK activation. Therefore, these results suggest that the anti-inflammatory effects of Schisandrin on P. gingivalis LPS-stimulated RAW 264.7 cells may be due to a reduction of NF-κB activity and induction of the expression of HO-1, leading to TNF-α, IL-1β, and IL-6 down-regulation.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Cell Nucleus; Cyclooctanes; Enzyme Activation; Gene Expression Regulation; Heme Oxygenase-1; Inflammation; Inflammation Mediators; Lignans; Lipopolysaccharides; Macrophages; Mice; NF-E2-Related Factor 2; NF-kappa B; Phosphatidylinositol 3-Kinases; Polycyclic Compounds; Porphyromonas gingivalis; Protein Transport; Proto-Oncogene Proteins c-akt; Signal Transduction; Up-Regulation

In this study, the herbal extracts of Schisandra chinensis were demonstrated to inhibit the contractions induced by acetylcholine (ACh) and serotonin (5-HT) in guinea pig ileum, and the 95% ethanol extract was more effective than the aqueous extract. Analysis with High Performance Liquid Chromatography (HPLC) indicated that schisandrin, schisandrol B, schisandrin A and schisandrin B were the major lignans of Schisandra chinensis, and the ethanol extract contained higher amount of these lignans than the aqueous extract. All four lignans inhibited the contractile responses to ACh, with EC(20) values ranging from 2.2±0.4μM (schisandrin A) to 13.2±4.7μM (schisandrin). The effectiveness of these compounds in relaxing the 5-HT-induced contraction was observed with a similar magnitude. Receptor binding assay indicated that Schisandra lignans did not show significant antagonistic effect on muscarinic M3 receptor. In Ca(2+)-free preparations primed with ACh or KCl, schisandrin A (50μM) attenuated the contractile responses to cumulative addition of CaCl(2) by 37%. In addition, schisandrin A also concentration-dependently inhibited ACh-induced contractions in Ca(2+)-free buffer. This study demonstrates that Schisandra chinensis exhibited relaxant effects on agonist-induced contraction in guinea pig ileum, with schisandrin, schisandrol B, schisandrin A and schisandrin B being the major active ingredients. The antispasmodic action of schisandrin A involved inhibitions on both Ca(2+) influx through L-type Ca(2+) channels and intracellular Ca(2+) mobilization, rather than specific antagonism of cholinergic muscarinic receptors.

Topics: Acetylcholine; Animals; Calcium; Chromatography, High Pressure Liquid; Cyclooctanes; Drugs, Chinese Herbal; Guinea Pigs; Ileum; In Vitro Techniques; Lignans; Male; Muscle Contraction; Muscle Relaxants, Central; Parasympatholytics; Plant Extracts; Plants, Medicinal; Polycyclic Compounds; Receptor, Muscarinic M3; Schisandra; Serotonin

In this study, ester-bond biphenyl cyclooctene lignans were efficiently hydrolytically degraded into free biphenyl cyclooctene lignans by ion exchange resin transformation and simultaneous removal of impurities by macroporous resin. The OH-type strongly basic anion exchange resin 201×7 was the best one, and the dynamic hydrolysis efficiency was 146.7±5.0%. HPD5000 macroporous resin, which offered higher adsorption and desorption capacities and faster adsorption than other resins. The purity of free biphenyl cyclooctene lignans in the product increased from 5.14±0.24% to 79.67±0.0.67%. After dynamic catalytic transformation by 201×7 resin combined with purification of HPD5000 resin, the yield and the purity of free biphenyl cyclooctene lignans in the product were 132.1±4.7% and 80.91±3.53%, respectively.

Topics: Adsorption; Analysis of Variance; Chromatography, Ion Exchange; Cyclooctanes; Dioxoles; Ethanol; Fruit; Hydrolysis; Ion Exchange Resins; Lignans; Plant Extracts; Polycyclic Compounds; Schisandra; Spectrometry, Mass, Electrospray Ionization; Temperature

To observe the effects of schizandrins on the learning and memory disorder in mice, and explore its mechanism.. The memory impairment model was established by using the pentobarbital sodium (20 mg x kg(-1)) intraperitoneally injected in mice. Schizandrins (0.5, 1.0, 2.0 g x kg(-1)) were administered through intragavage for consecutive 14 days. Morris Water Maze test was used to evaluate the impairment of learning and memory. The energy of superoxide dismutase (SOD), nitric oxide (NO) and catalase (CAT) of brain tissue were measured. And the positive expression of nuclear transcription factor-kappaB p65 (NF-kappaB p65), caspase-3 in the hippocampus CA1 region were determined by immunohistochemical analysis. At the cellular level, 24 h after schizandrins (0.062 5, 0.125, 0.25 g x L(-1)) were pre-administered, the apoptosis model of PC12 cell was induced by H2O2, and activity of PC12 cell was detected by MTT colorimetric assay, the energy of NO in cell serum were measured. The expression of Bcl-2 was determined by the combination of immunocytochemical staining and image analysis software.. Morris Water Maze test showed that the model group mice took shorter searching time and distance on the previous flat area than those in the control group (P < 0.05), which could be prolonged after schizandrins treatment (P < 0.05, P < 0.01). Compared with the control group, the level of NO increased while the activity of SOD, CAT decreased in the model group (both P < 0.01). After treated with schizandrins, the level of NO significantly decreased (P < 0.01), while the activity of SOD increased (P < 0.01). Immunohistochemistry analysis showed that the protein expression of NF-kappaB p65, Caspase-3 in the hippocampal CA1 region significantly increased after modeling, while schizandrins (1.0 g x kg(-1)) can significantly inhibit the protein expression of NF-kappaB p65, Caspase-3 (P < 0.05, P < 0.01). Compared with the H2O2, model group, schizandrins (0.125, 0.25 g x L(-1)) can significantly increased PC12 cell activity and decreased the NO level (P < 0.05, P < 0.01), the expression of Bcl-2 in the schizandrins group (0.125, 0.25 g x L(-1)) was up-regulated.. Schizandrins could improve the learning-memory dysfunction induced by the sodium pentobarbital in mice, and its protective mechanism is related to the lowering oxidative damage and inhibiting the cell apoptosis through up-regulating the expression of Bcl-2.

Topics: Animals; Apoptosis; Behavior, Animal; CA1 Region, Hippocampal; Caspase 3; Cell Line; Cyclooctanes; Disease Models, Animal; Drugs, Chinese Herbal; Female; Learning Disabilities; Lignans; Male; Memory Disorders; Mice; Nitric Oxide; Oxidative Stress; PC12 Cells; Polycyclic Compounds; Proto-Oncogene Proteins c-bcl-2; Rats; Superoxide Dismutase; Transcription Factor RelA

To investigate the pharmacokinetics and tissue distribution of Schisandra chinensis in mice.. Schisandrin in mice plasma and tissues including heart, liver, spleen, lung and kidney was quantitatively determined by HPLC.. The concentration-time curve of Schisandra chinensis extract was described by a single compartment model, Cmax was (2.17 +/- 0.27) mg/ mL, t(max) was (1.00 +/- 0.32) h, AUC0-->infinity, was (4.07 +/- 0.62) mg x h/mL. The sequence of distribution of schisandrin in mice body was as follows: liver > plasma > kidney > lung > heart > spleen.. The distribution of extract in the body is abroad. Liver has relative high concentration of schisandrin, which is beneficial to the treatment of hepatic disease.

Topics: Administration, Oral; Animals; Area Under Curve; Chromatography, High Pressure Liquid; Cyclooctanes; Fruit; Kidney; Lignans; Liver; Lung; Male; Mice; Plant Extracts; Polycyclic Compounds; Schisandra; Spleen; Tissue Distribution

To study the chemical constituents of vinegar Schisandra chinensis.. Column chromatography was used in the isolation procedure. The structures of isolated compounds were elucidated by spectral data.. Five compounds were isolated and their structures were identified as kadsuranin (I), beta-sitosterol (II), schizandrin (III), 5,5'-[oxybis (methylene)] bis-2-furancarboxaldehyde (IV) and (NH)-form-2-Hydroxyquinoline4-carboxylic acid (V).. Compound 5 is isolated from this genus for the first time.

Topics: Acetic Acid; Cyclooctanes; Fruit; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure; Plants, Medicinal; Polycyclic Compounds; Schisandra; Sitosterols; Technology, Pharmaceutical

Schizandrin is one of the main dibenzocyclooctadiene lignans present in the fruit of Schisandra chinensis (Schisandraceae). Biological activities including hepatoprotective, antiviral and neuroprotective effects of schizandrin and other dibenzocyclooctadiene lignans have been reported previously. However, the antiproliferative effect of schizandrin against human cancer cells has been poorly determined to date. This study examined the antiproliferative effect of schizandrin in human breast cancer cells. Schizandrin exhibited growth inhibitory activities in cultured human breast cancer cells, and the effect was the more profound in estrogen receptor (ER)-positive T47D cells than in ER-negative MDA-MB-231 cells. When treated with the compound in T47D cells, schizandrin induced the accumulation of a cell population in the G0/G1 phase, which was further demonstrated by the induction of CDK inhibitors p21 and p27 and the inhibition of the expression of cell cycle checkpoint proteins including cyclin D1, cyclin A, CDK2 and CDK4. These results suggest that schizandrin inhibits cell proliferation through the induction of cell cycle arrest with modulating cell cycle-related proteins in human breast cancer cells.

Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Cycle; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor Proteins; Cyclooctanes; Female; Humans; Lignans; Molecular Structure; Polycyclic Compounds; Schisandra

A sensitive and specific method based on liquid chromatography-tandem mass spectrometry using electrospray ionization (LC-ESI-MS/MS) has been developed for the determination of Schisandrin and Schisandrin B in rat plasma. A 100 microL plasma sample was extracted by methyl tert-butyl ether after spiking the samples with nimodipine (internal standard) and performed on an XTerra(R)MS-C(18) column (150 mm x 2.1 mm, 3.5 mum) with the mobile phase of acetonitrile-water-formic acid (80:20:0.2, v/v) at a flow rate of 0.2 mL/min in a run time of 8.5 min. The lower limit of quantification of the method was 40 ng/mL for Schisandrin and 20 ng/mL for Schisandrin B. The method showed reproducibility with intra-day and inter-day precision of less than 13.8% RSD, as well as accuracy, with inter- and intra-assay accuracies between 93.5 and 107.2%. Finally, the LC-ESI-MS/MS method was successfully applied to study the pharmacokinetics of Schisandrin and Schisandrin B in rats after administration of Wurenchun commercial formulations to rats.

Topics: Animals; Chromatography, Liquid; Cyclooctanes; Drugs, Chinese Herbal; Lignans; Male; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

Schizandrin is recognized as the major absorbed effective constituent of Fructus schisandrae, which is extensively applied in Chinese medicinal formula. The present study aimed to profile the phase I metabolites of schizandrin and identify the cytochrome P450 (CYP) isoforms involved. After schizandrin was incubated with human liver microsomes, three metabolites were isolated by high-performance liquid chromatography (HPLC) and their structures were identified to be 8(R)-hydroxyl-schizandrin, 2-demethyl-8(R)-hydroxyl-schizandrin, 3-demethyl-8(R)-hydroxyl-schizandrin, by liquid chromatography-mass spectrometry (LC-MS), (1)H-nuclear magnetic resonance (NMR), and (13)C-NMR, respectively. A combination of correlation analysis, chemical inhibition studies, assays with recombinant CYPs, and enzyme kinetics indicated that CYP3A4 was the main hepatic isoform that cleared schizandrin. Rat and minipig liver microsomes were included when evaluating species differences, and the results showed little difference among the species. In conclusion, CYP3A4 plays a major role in the biotransformation of schizandrin in human liver microsomes. Minipig and rat could be surrogate models for man in schizandrin pharmacokinetic studies. Better knowledge of schizandrin's metabolic pathway could provide the vital information for understanding the pharmacokinetic behaviours of schizandrin contained in Chinese medicinal formula.

Topics: Animals; Catalysis; Chromatography, High Pressure Liquid; Cyclooctanes; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Humans; Ketoconazole; Lignans; Mass Spectrometry; Metabolic Networks and Pathways; Microsomes, Liver; Polycyclic Compounds; Rats; Swine; Swine, Miniature; Troleandomycin

A simple and sensitive high performance liquid chromatography method with photodiode array detection (HPLC-DAD) was developed for simultaneous determination of eight bioactive constituents (schisandrin, schisandrol B, schisantherin A, schisanhenol, anwulignan, deoxyshisandrin, schisandrin B and schisandrin C) in the ripe fruit of Schisandra sphenanthera and its traditional Chinese herbal preparations Wuzhi-capsule by optimizing the extraction, separation and analytical conditions of HPLC-DAD. The chemical fingerprint of S. sphenanthera was established using raw materials of 15 different origins in China. The chromatographic separations were obtained by an Agilent Eclipse XDB-C18 reserved-phase column (250 mm x 4.6 mm i.d., 5 microm) using gradient elution with water-formic acid (100:0.1, v/v) and acetonitrile, at a flow rate of 1.0 mL min(-1), an operating temperature of 35 degrees C, and a wavelength of 230 nm. The constituents were confirmed by (+) electrospray ionization LC-MS. The new method was validated and was successfully applied to simultaneous determination of components in 13 batches of Wuzhi-capsule. The results indicate that this multi-component determination method in combination with chromatographic fingerprint analysis is suitable for quantitative analysis and quality control of S. sphenanthera.

Topics: Chromatography, High Pressure Liquid; Cyclooctanes; Dioxoles; Fruit; Lignans; Mass Spectrometry; Plant Extracts; Polycyclic Compounds; Reproducibility of Results; Schisandra

Four derivatives of schisandrin, a major dibenzo[a,c]cyclooctadiene lignan of Schisandra chinensis (Turcz.) Baillon were synthesized and structurally characterized by means of NMR and mass spectroscopy. Furthermore, axial chirality of the biphenyl system was determined by comparison of calculated with measured circular dichroism (CD) spectra. Three of the obtained derivatives showed a ring contraction during chemical modification. While the original lignans were inactive on the performed bioassays, the compounds which showed the cycloheptadiene skeleton revealed remarkable activities. For the inhibition of LTB(4) production the IC(50) values of aR-6,7-dihydro-6-(1'-hydroxyethyl)-3,9-dimethoxy-6-methyl-5H-dibenzo[a,c]cycloheptene-1,2,10,11-tetraol (6) and aR-6-(1'-iodoethyl)-1,2,3,9,10,11-hexamethoxy-6-methyl-5H-dibenzo[a,c]cycloheptene (8) were 4.2+/-0.3microM and 4.5+/-0.2microM, respectively. aR-6,7-Dihydro-6-(1'-hydroxyethyl)-6-methyl-5H-dibenzo[a,c]cycloheptene-1,2,3,9,10,11-hexaol (5) revealed dual inhibition on COX-2 (IC(50) 32.1+/-2.5microM) and on LTB(4) production (37.3+/-5.5% inhibition at 50microM).

Topics: Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Circular Dichroism; Cyclooctanes; Cyclooxygenase 1; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Indicators and Reagents; Leukotriene B4; Lignans; Lipoxygenase Inhibitors; Magnetic Resonance Spectroscopy; Polycyclic Compounds; Schisandra; Spectrometry, Mass, Electrospray Ionization; Structure-Activity Relationship

Asthma comprises a triad of reversible airway obstruction, bronchial smooth muscle cell hyperreactivity to bronchoconstrictors, and chronic bronchial inflammation. Clinical and experimental findings have established eosinophilia as a sign of allergic disorders. In the present investigation, we evaluated the anti-asthmatic effects of schizandrin and its underlying mechanisms in an in vivo murine asthmatic model. To accomplish this, female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and examined for the following typical asthmatic reactions: increased numbers of eosinophils and other inflammatory cells in bronchoalveolar lavage fluid (BALF); production of Th1 cytokines (such as tumor necrosis factor (TNF)-α in BALF); production of Th2 cytokines (such as interleukin IL-4 and IL-5) in BALF; presence of total and OVA-specific immunoglobulins (Ig)E in serum; presence of oxidative stress; hyperplasia of goblet cells in the lung; and marked influx of inflammatory cells into the lung. Our results collectively show that schizandrin exerts profound inhibitory effects on accumulation of eosinophils into the airways and reduces the levels of IL-4, IL-5, IFN-γ, and TNF-α in BALF. Additionally, schizandrin suppresses the production of reactive oxygen species (ROS) in a dose-dependent manner, and inhibits goblet cell hyperplasia and inflammatory cell infiltration in lung tissue. Thus, schizandrin has anti-asthmatic effects, which seem to be partially mediated by reduction of oxidative stress and airway inflammation, in a murine allergic asthma model. These results indicate that schizandrin may be an effective novel therapeutic agent for the treatment of allergic asthma.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Bronchoalveolar Lavage Fluid; Cyclooctanes; Cytokines; Disease Models, Animal; Eosinophils; Female; Goblet Cells; Hyperplasia; Immunoglobulin E; Lignans; Lung; Mice; Mice, Inbred BALB C; Oxidative Stress; Polycyclic Compounds; Reactive Oxygen Species; Th1 Cells; Th2 Cells

Wurenchun is the alcohol extract from Fructus Schisandrae Chinensis, which has good efficiency in lowering abnormal serum glutamic pyruvic transaminase (SGPT) level of patients suffering from acute or chronic hepatitis. The main purpose of this work is to prepare self-emulsifying drug delivery systems (SEDDS) for enhancing the solubility, dissolution rate, and oral bioavailability of poorly water-soluble traditional Chinese medicines, Wurenchun.. Pseudoternary phase diagrams were used to evaluate the efficient self-emulsification domains, and particle size distributions of resultant emulsions were determined. The dissolution test was performed according to the second method of Chinese Pharmacopoeia dissolution procedure. The pharmacokinetic study in rats for the optimized formulation was performed and compared to commercial capsules.. The optimized formulation for bioavailability assessment consisted of 20% oleic acid, 65% Tween 20, and 15% Transcutol P. The mean droplet size distribution of the optimized SEDDS was approximately 240 nm when diluted with 1000-fold volume of the distilled water. The in vitro dissolution rates of the active components of Wurenchun SEDDS were significantly higher than those of the commercial capsules. SEDDS have significantly increased the C(max) and area under the curve) (AUC) of Wurenchun compared to reference capsules (P < 0.05). And the relative bioavailability of SEDDS for schisandrin and schisandrin B was 292.2% and 205.8% compared to the commercial capsules, respectively.. The results suggest the potential use of SEDDS to improve oral absorption of the sparingly soluble drugs or traditional Chinese medicine, such as Wurenchun.

Topics: Administration, Oral; Animals; Area Under Curve; Biological Availability; Cyclooctanes; Drug Delivery Systems; Drugs, Chinese Herbal; Emulsions; Excipients; Fruit; Lignans; Male; Particle Size; Plant Extracts; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Schisandra; Solubility

Extraction and purification conditions of lignans from the fruits and seeds of Schisandra chinensis (Turcz.) were investigated through an orthogonal design of L(9)(3(4)) assay and macroporous resin technology. The extraction was optimized using 95% ethanol. For purification, the extract was dissolved in 30% ethanol, then adsorbed on a AB-8 macroporous resin and eluted with 30% ethanol and 70% ethanol successively, the latter resulting in a residue containing 65.2% of lignans. By HPLC analysis schisandrin, deoxyschisandrin and gamma-schisandrin were quantitatively determined. UMR 106 cells were used to examine the stimulatory activity of the lignans on osteoblasts in vitro. The lignans stimulated the proliferation of and the activity of alkaline phosphatase in the osteoblasts indicating their potential activity against osteoporosis.

Topics: Alkaline Phosphatase; Animals; Cell Line; Cell Proliferation; Chromatography, High Pressure Liquid; Cyclooctanes; Enzyme Activators; Lignans; Osteoblasts; Plant Extracts; Polycyclic Compounds; Rats; Schisandra

To investigate the effects of schisandra on the function of the pituitary-adrenal cortex, gonadal axis and carbohydrate metabolism in male rats undergoing experimental chronic psychological stress, navigation and strenuous exercise.. Thirty-four SD rats were randomly allocated into a non-stress group (Group A), a stress control group (Group B) and a schisandra group (Group C). The latter two groups received 10 days of Benford's high-intensity training, followed by 3 hours of wearing floating with psychological stress and another 3 hours of running at the speed of 26.7 m/min. Then blood samples were immediately obtained for the measurement of the levels of testosterone (T), corticosterone (CORT), luteinizing hormone (LH) and blood glucose (Glu). Meanwhile the adrenal gland was excised and its cortex ultrastructure observed under the electron microscope.. The Glu level was increased while the T level decreased significantly in Group B as compared with Group A. The CORT level remained unchanged in Group B. Both the Glu and CORT levels were significantly reduced in Group C in comparison with B. However, no significant differences were found in serum LH levels among the three groups. And electron microscopy revealed a reduction of lipid droplets and apoptosis of the adrenal cortex cells in Group B as compared with C.. Schisandra can reduce the levels of CORT and Glu and protect the structure of the adrenal cortex.

Topics: Animals; Blood Glucose; Carbohydrate Metabolism; Corticosterone; Cyclooctanes; Hyperkinesis; Lignans; Male; Physical Conditioning, Animal; Phytotherapy; Pituitary-Adrenal System; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Schisandra; Stress, Psychological

Eosinophilia have been implicated in a broad range of diseases, most notably allergic conditions (e.g. asthma, rhinitis and atopic dermatitis) and inflammatory diseases. These diseases are characterized by an accumulation of eosinophils in the affected tissue. Defining the mechanisms that control the recruitment of eosinophil is fundamental to understanding how these diseases progress and identifying a novel target for drug therapy. Accordingly, this study was conducted to evaluate the regulatory effect of Schizandrae Fructus (SF) on the expression of eotaxin, an eosinophil-specific chemokine released in respiratory epithelium following allergic stimulation, as well as its effects on eosinophil migration. To accomplish this, human epithelial lung cells (A549 cell) were stimulated with a combination of TNF-alpha (100ng/ml) and IL-4 (100ng/ml) for 24h. The cells were then restimulated with TNF-alpha (100ng/ml) and IL-1beta (10ng/ml) to induce the expression of chemokines and adhesion molecules involved in eosinophil chemotaxis for another 24h. Next, the samples were treated with various concentrations of Schizandrae Fructus (SF) (1, 10, 100, 1000microg/ml) or one of the major constituents of SF, schizandrin (0.1, 1, 10, 100microg/ml), after which following inhibition effect assay was performed triplicates in three independence. The levels of eotaxin in secreted proteins were suppressed significantly by SF (100 and 1000microg/ml, p<0.01) and schizandrin (10 and 100microg/ml, p<0.01). In addition, SF (1, 10, 100 and 1000microg/ml) decreased mRNA expression levels in A549 cells significantly (p<0.01). Eosinophil recruitment to lung epithelial cells was also reduced by SF, which indicates that eotaxin plays a role in eosinophil recruitment. Furthermore, treatment with SF suppressed the expression of another chemokine, IL-8 (0.1 and 1microg/ml SF, p<0.01), as well as intercellular adhesion molecule-1 (10 and 100microg/ml SF, p<0.01) and vascular cell adhesion molecule-1 (0.1 and 1microg/ml SF, p<0.05), which are all related to eosinophil migration. Taken together, these findings indicate that SF may be a desirable medicinal plant for the treatment of allergic diseases.

Topics: Cell Line; Cell Migration Inhibition; Chemokines, CC; Chemotaxis, Leukocyte; Cyclooctanes; Cytokines; Eosinophilia; Eosinophils; Epithelial Cells; Fruit; Humans; Intercellular Adhesion Molecule-1; Lignans; Lung; Plant Extracts; Polycyclic Compounds; Respiratory Mucosa; RNA, Messenger; Schisandra; Vascular Cell Adhesion Molecule-1

Schisandrin is the main active ingredient isolated from Schisandra chinensis Baill. Recent studies have demonstrated that schisandrin exhibits anti-inflammatory effects in vivo and in vitro. In this study, we examined whether the order of lipopolysaccharide (LPS) treatment affects the mechanism of schisandrin anti-inflammatory activity. We found that the antiinflammatory mechanisms are not the same depending on whether macrophages were treated with schisandrin before or after LPS. The main difference is that inhibitor kappaBalpha (IkappaBalpha) degradation was not inhibited when macrophages were pretreated by LPS before schisandrin and was weakly inhibited when macrophages were pretreated by schisandrin before LPS.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Cyclooctanes; Cyclooxygenase 2; Dose-Response Relationship, Drug; I-kappa B Proteins; JNK Mitogen-Activated Protein Kinases; Lignans; Lipopolysaccharides; Macrophages; Mice; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Polycyclic Compounds; Time Factors; Transcription Factors

The systems of mobile phase for the determination of gamma-schisandrin in Schisandra chinensis and its preparations were developed by high performance liquid chromatography (HPLC). The separation was performed on a Shim-pack VP-ODS column (250 mm x 4.6 mm, 5 microm) at 30 degrees C, the detection wavelength was set at 285 nm and the flow rate was 1.0 mL/min. Retention times and separation were investigated in mixed solution of three reference substances (gamma-schisandrin, anwulignan, and deoxyschizandrin) and methanol extract of Schisandra chinensis by different systems and proportions of mobile phases to select optimal conditions for the determination of gamma-schisandrin. The results showed that the complete separation of gamma-schisandrin and anwulignan was difficult in the systems of methanol-water and methanol-acetic acid-water. The separation of gamma-schisandrin, anwulignan and deoxyschizandrin can be completed in the systems of acetonitrile-methanol-water and acetonitrile-acetic acid-water when their proportions were suitable. The mobile phase of acetonitrile-methanol-water (17:58:25, v/v/v) was selected for the determination of deoxyschizandrin, gamma-schisandrin and anwulignan in Schisandra chinensis and Hugan tablets. The determination results of the three substances were satisfactory with the relative standard deviations (n = 4) ranged from 0.95% to 5.8%, and the average recoveries ranged from 94.50% to 105.6%. The efficiency of separation and the results of determination were satisfactory for the real samples.

Topics: Chromatography, High Pressure Liquid; Cyclooctanes; Drugs, Chinese Herbal; Lignans; Polycyclic Compounds; Schisandra

To study the preparation method of Schisandra total lignanoids enteric (SLE) nanoparticles and evaluate its pharmacokinetics in rats, SLE nanoparticles were prepared by modified emulsion solvent diffusion method. The properties of SLE nanoparticles were evaluated of morphology, mean diameter and entrapment efficiency. An HPLC method was employed to determine the concentration of deoxyschisandrin (QS) and schisantherin A (SA) in plasma, which were used as an index of Schisandra total lignanoids, and the bioavailability of the nanoparticles was compared with the reference group by oral administration using SD rats. The nanoparticles observed by transmission electronmicroscopy were round, and the mean particle sizes of SLE were (36.7 +/- 4.4) nm. Entrapment efficiency of QS and SA were (97.5 +/- 0.7)% and (91.3 +/- 0.8)%, respectively. Its pharmacokinetic process calculated with 3p97 software was fitted to a one-compartment model. The pharmacokinetic parameters showed sustained-release property. Compared with reference formulation, the AUCs of SLE nanoparticles were 2.3 and 5.8 times separately. These results suggested that the incorporation into Eudragit S100 of Schisandra total lignanoids can improve the bioavailability.

Topics: Animals; Area Under Curve; Biological Availability; Cyclooctanes; Female; Lignans; Male; Nanoparticles; Particle Size; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Schisandra

To determine lignan content in the vine stem of Schisandra chinensis during 12 months and provide the scientific basis for the development and utilization of the resources.. Analysis was carried out on an Eclipse XDB C18 column eluted with a mixture of methanol-acetonitrile-water (43: 28: 29) as the mobile phase. The flowrate was 1.0 mL x min(-1), and the detection wavelength was set at 250 nm. Schisandrin, deoxyschizandrin and schisandrin B were used as reference substance, and the external standard method was used.. The content of three constituents in the vine stem varied under different months. Schisandrin's maximum is 2.3 mg x g(-1) in December, minimum is 1.4 mg x g(-1) in April. A Deoxyschizandrin's maximum is 0.8 mg x g(-1) in November, minimum is 0.4 mg x g(-1) in March; Schisandrin B's maximum is 3.0 mg x g(-1) in January, minimum is 1.1 mg x g(-1) in April.. The collection seasons for the vine stem of S. chinensis are autumn and winter.

Topics: Chromatography, High Pressure Liquid; Cyclooctanes; Lignans; Plant Stems; Polycyclic Compounds; Schisandra

Two new dibenzocyclooctadiene lignans, neglschisandrins C-D (1-2), were isolated from the stems of Schisandra neglecta. Their structures and stereochemistries were elucidated by spectroscopic methods, including 1D- and 2D-NMR and HR-ESI-MS techniques.

Topics: Cyclooctanes; Lignans; Magnetic Resonance Spectroscopy; Polycyclic Compounds; Schisandra

Schisandrin is the main active ingredient isolated from the fruit of Schisandra chinensis Baill. Recent studies have demonstrated that schisandrin exhibits anti-oxidative effects in vivo. In the present study, the effect of schisandrin on plasma nitrite concentration in lipopolysaccharide (LPS)-treated mice was evaluated. It also significantly inhibited carrageenan-induced paw edema and acetic acid-induced vascular permeability in mice. Furthermore, schisandrin had a protective effect on lipopolysaccharide (LPS)-induced sepsis. In vitro, our results are the first that show that the anti-inflammatory properties of schisandrin result from the inhibition of nitric oxide (NO) production, prostaglandin E(2) (PGE(2)) release, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, which in turn results from the inhibition of nuclear factor-kappaB (NF-kappaB), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activities in a RAW 264.7 macrophage cell line.

Topics: Animals; Anti-Inflammatory Agents; Capillary Permeability; Cell Line; Cyclooctanes; Cyclooxygenase 2; Dinoprostone; Fruit; Gene Expression Regulation; Inflammation; Lignans; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred ICR; Nitric Oxide; Nitric Oxide Synthase Type II; Nitrites; Polycyclic Compounds; Schisandra; Sepsis

The lignan meso-nordihydroguaiaretic acid is known to undergo spontaneous oxidation in alkaline solution. In the presence of the trapping agent glutathione, the major oxidation products are consistent with the formation of a meso-nordihydroguaiaretic acid ortho-quinone. In the absence of a trapping agent however, the major oxidation product of meso-nordihydroguaiaretic acid in aqueous solution is a unique, stable schisandrin-like dibenzocyclooctadiene lignan that may be responsible for some of the biological effects of nordihydroguaiaretic acid.

Topics: Cyclooctanes; Lignans; Masoprocol; Molecular Structure; Oxidation-Reduction; Polycyclic Compounds; Stereoisomerism

To study the lignan components of different processed products of Schisandra chinensis fruits, the study was conducted with electrospray ionization mass spectrometry (ESI-MS) and high performance liquid chromatography (HPLC). There was no new lignan components detected from the products obtained with different processed methods, the difference was in the content of lignan components. The method is accurate and effective, which can be used to evaluate the quality of different processed products of Schisandra chinensis fruits.

Topics: Chromatography, High Pressure Liquid; Cyclooctanes; Dioxoles; Drug Compounding; Drugs, Chinese Herbal; Fruit; Hot Temperature; Lignans; Plants, Medicinal; Polycyclic Compounds; Quality Control; Schisandra; Spectrometry, Mass, Electrospray Ionization

Nortriterpenoids, sphenadilactone C (1) and sphenasin A (2), together with four known lignans (3-6), were isolated from the leaves and stems of Schisandra sphenanthera. Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and compound 2 was further confirmed by single-crystal X-ray diffraction. Compound 1 features a partial enol moiety and an acetamide group in its structure. In addition, compounds 1, 3-6 showed weak anti-HIV-1 activity with EC(50) values in the range of 15.5-29.5 microg/mL.

Topics: Cell Line; Cyclooctanes; Dioxoles; HeLa Cells; HIV-1; Humans; Lignans; Microbial Sensitivity Tests; Plant Extracts; Polycyclic Compounds; Schisandra; Triterpenes

The present study investigated the effect of schizandrin, a component of the fruit of Schizandra chinesis Baill (Fructus Schizandrae), on memory impairment in rats. Scopolamine (0.5 mg/kg, i.p.), a non-selective muscarinic receptor antagonist, markedly impaired spatial memory in an eight-arm radial maze. A higher dose of scopolamine (3 mg/kg, i.p.) also impaired the passive avoidance response. Schizandrin (1 and 10 mg/kg, p.o.) significantly reversed the scopolamine-induced impairment of spatial memory. Similarly, schizandrin (1 mg/kg, p.o.) significantly reversed the scopolamine-induced impairment of the passive avoidance response. Moreover, in mice, schizandrin (1 and 10 mg/kg, p.o.) enhanced tremors induced by oxotremorine, a muscarinic M(1) receptor agonist. Taken together these findings suggest that schizandrin reverses scopolamine-induced memory impairment, in part, by enhancing cholinergic function, and that schizandrin might be useful for treating memory deficits.

Topics: Animals; Avoidance Learning; Cyclooctanes; Dose-Response Relationship, Drug; Lignans; Male; Maze Learning; Memory Disorders; Molecular Structure; Muscarinic Antagonists; Oxotremorine; Phytotherapy; Polycyclic Compounds; Rats; Rats, Wistar; Schisandra; Scopolamine

Schizandrae chinensis, a traditional Chinese medicine herb, has been used to treat hepatitis B disease in Chinese hospital clinic. We have isolated two bioactive compounds, deoxyschizandrin and gamma-schizandrin, from S. chinensis. In the present, we reported that deoxyschizandrin and gamma-schizandrin could induce apoptosis in human promyelocytic leukemia cells (HL-60), as characterized by DNA fragmentation and poly (ADP) ribose polymerase (PARP) cleavage. Further molecular analysis showed that deoxyschizandrin and gamma-schizandrin caused the loss of mitochondrial membrane potential (DeltaPsim), cytochrome c release from mitochondrion to cytosol, truncation of Bid protein, and activation of caspase-3 and -9. However, they did not increase the intracellular level of reactive oxygen species (ROS). Antioxidants such as N-acetyl cysteine (NAC) and catalase did not block the apoptosis induced by deoxyschizandrin or gamma-schizandrin. These findings suggest that deoxyschizandrin and gamma-schizandrin-induced apoptosis in HL-60 cells involved ROS-independent mitochondrial dysfunction pathway.

Topics: Apoptosis; Caspase 3; Cell Survival; Cyclooctanes; DNA Fragmentation; HL-60 Cells; Humans; Lignans; Molecular Biology; Phytotherapy; Plant Preparations; Polycyclic Compounds; Schisandra; Structure-Activity Relationship

Sheng-Mai-San (SMS) is a famous traditional Chinese medicine (TCM) recipe, containing Radix Ginseng (Panax ginseng C.A. Mey., Araliaceae), Radix Ophiopogonis (Ophiopogon japonicus (Thunb.) Ker-Gawl., Liliaceae) and Fructus Schisandrae (Schisandra chinensis (Turcz.) Baill., Magnoliaceae), and has been used more than one thousand years. In this research, pharmacokinetics of one component of this TCM recipe was studied. Schizandrin is the main absorbed effective ingredient of Fructus Schisandrae and its pharmacokinetics were studied following oral administration of pure schizandrin, Fructus Schisandrae aqueous extract, and SMS decoction in rats with approximately the same dose of 5mg/kg. At different time points (0, 0.083, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12h) after administration, the concentrations of schizandrin in rat plasma were determined by LC-MS, and main pharmacokinetic parameters were estimated. It was found that both AUC0-tn and T1/2 of schizandrin in Fructus Schisandrae aqueous extract and in SMS decoction were increased significantly (p<0.05) comparing with that in monomer. The content assay also revealed that the concentrations of lignans would increase when SMS decocting, comparing with Fructus Schisandrae. These results indicate that some ingredients in SMS may increase the dissolution of schizandrin when decocting in vitro, and delay its elimination and enhance its bioavailability in rat.

Topics: Administration, Oral; Animals; Area Under Curve; Biological Availability; Chromatography, Liquid; Cyclooctanes; Drugs, Chinese Herbal; Female; Fruit; Half-Life; Lignans; Mass Spectrometry; Medicine, Chinese Traditional; Ophiopogon; Panax; Polycyclic Compounds; Random Allocation; Rats; Rats, Sprague-Dawley; Schisandra; Solubility; Time Factors

Fructus Schizandrae (FS) is commonly used as a tonic in traditional Chinese medicine. Recently, FS was found to significantly improve liver dysfunction in chronic hepatitis patients. The present study was to assess the reversal effect of five schizandrins and crude extract from FS (named LCC) on multidrug resistance (MDR) of cancer cells, both in vitro and in vivo. Chemically, the five schizandins are derivatives of dibenzo-(a, c)-cyclooctene lignan with distinct structures differing from any known MDR reversal agents.. A panel of sensitive and resistant cancer cell lines were treated with various concentrations of LCC and schizandrins. Drug sensitivity, accumulation of Doxorubicin (Dox), expression of P-glycoprotein and protein kinase C (PKC), and apoptosis were determined in vitro. The in vivo effect was tested in nude mice grafted with sensitive and resistant human epidermal cancer cell line to vincristine (VCR) (KB, KBv200).. The tested five compounds at 25 muM showed various levels of MDR reversal activity, of which, schizandrin A (Sin A) was the most potent one. Sin A reversed VCR resistance in KBv200 cells, MCF-7/Dox cells and Bel7402 cells by 309-, 38-, and 84-folds, respectively. Also, Sin A reversed the resistance of Dox in the above cancer cell lines. LCC at 25 mug/ml reversed VCR resistance by 619-folds in KBv200, 181-folds in MCF-7/Dox cell line, and 1,563-folds in innate resistance of human hepatic cellular carcinoma Bel7402 cells to VCR. Furthermore, LCC and its active component Sin A potently reversed the cross-resistance to paclitaxel in those cell lines. Both Sin A and LCC markedly increased intracellular Dox accumulation and enhanced apoptosis, down-regulated Pgp protein and mRNA and total PKC expression in MDR cells. Coadministration of LCC (p.o.) significantly potentiated the inhibitory effect of VCR (i.p.) on tumor growth in nude mice bearing KBv200 xenograft.. The LCC and its active component Sin A have remarkable reversal effect on MDR in cancer cells by inhibition of both the function and expression of Pgp and total PKC.

Topics: Animals; Apoptosis; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line, Tumor; Cyclooctanes; Dioxoles; Doxorubicin; Drug Evaluation, Preclinical; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drugs, Chinese Herbal; Fruit; Genes, MDR; Humans; Lignans; Mice; Mice, Nude; Neoplasm Proteins; Phytotherapy; Plant Preparations; Polycyclic Compounds; Protein Kinase C; Schisandra; Xenograft Model Antitumor Assays

Two new dibenzocyclooctene lignans, neglschisandrins A-B (1-2), were isolated from the stems of Schisandra neglecta. Their structures and stereochemistries were elucidated by spectroscopic methods, including 1D- and 2D-NMR and HR-ESI-MS techniques.

Topics: Cyclooctanes; Lignans; Magnetic Resonance Spectroscopy; Polycyclic Compounds; Schisandra

The neuroprotective effect of schizandrin on the glutamate (Glu)-induced neuronal excitotoxicity and its potential mechanisms were investigated using primary cultures of rat cortical cells. After exposure of primary cultures of rat cortical cells to 10 microM Glu for 24 h, cortical cell cultures exhibited remarkable apoptotic death. Pretreatment of the cortical cell cultures with schizandrin (10, 100 microM) for 2 h significantly protected cortical neurons against Glu-induced excitotoxicity. The neuroprotective activity of schizandrin was the most potent at the concentration of 100 microM. Schizandrin reduced apoptotic characteristics by DAPI staining in Glu-injured cortical cell cultures. In addition, schizandrin diminished the intracellular Ca2+ influx, inhibited the subsequent overproduction of nitric oxide (NO), reactive oxygen species (ROS), and cytochrome c, and preserved the mitochondrial membrane potential. Furthermore, schizandrin also increased the cellular level of glutathione (GSH) and inhibited the membrane lipid peroxidation malondialdehyde (MDA). As indicated by Western blotting, schizandrin attenuated the protein level changes of procaspase-9, caspase-9, and caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Taken together, these results suggest that schizandrin protected primary cultures of rat cortical cells against Glu-induced apoptosis through a mitochondria-mediated pathway and oxidative stress.

Topics: Animals; Apoptosis; Calcium; Caspases; Cells, Cultured; Cerebral Cortex; Cyclooctanes; Cytochromes c; Dizocilpine Maleate; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Glutamic Acid; Glutathione; Lignans; Lipid Peroxidation; Membrane Potential, Mitochondrial; Mitochondria; Neurons; Neuroprotective Agents; Nitric Oxide; Oxidative Stress; Poly(ADP-ribose) Polymerases; Polycyclic Compounds; Rats; Reactive Oxygen Species

Neurodegenerative brain disorders such as Alzheimer's disease (AD) have been well investigated. However, significant methods for the treatment of the promotion and progression of AD are unavailable to date. Recent studies suggested that the redox imbalance and the accumulation of amyloid-beta (Abeta) peptide occurring in the brain of AD patients lead to oxidatively-induced apoptotic cell death. Here, we show the effects of Shengmai-san (SMS) on Abeta-induced cytotoxicity in PC-12 cells. SMS dose-dependently attenuated the cytotoxicity by Abeta incubation and also prevented the morphological damage in neurites of the PC-12 cells. Hemeoxygenase-1 and glutathione peroxidase-1 expressions were increased by SMS pretreatment. SMS decreased the phosphorylation level of c-jun amino-terminal kinase (JNK) and the activity of caspase-3, which were enhanced by Abeta incubation. Of importance, SMS treatment promoted neurite outgrowth. These data demonstrated dual roles of SMS in PC-12 cells. SMS prevents the apoptosis through the enhancement of anti-oxidant enzymes and inhibition of the JNK signaling pathway with the promotion of nerve cell maturation, thus suggesting benefits of SMS for the treating of neurodegenerative diseases. It may also be beneficial not only for the treatment of brain disorders but also for other diseases caused by oxidative stress.

Topics: alpha-Tocopherol; Amyloid beta-Peptides; Animals; Apoptosis; bcl-Associated Death Protein; Caspase 3; Caspase Inhibitors; Cell Survival; Chromatography, High Pressure Liquid; Cyclooctanes; Dioxoles; DNA Fragmentation; Dose-Response Relationship, Drug; Drug Combinations; Drugs, Chinese Herbal; Flow Cytometry; Glutathione Peroxidase; Glutathione Peroxidase GPX1; Heme Oxygenase-1; Lignans; MAP Kinase Kinase 4; Oxidation-Reduction; PC12 Cells; Polycyclic Compounds; Rats; Time Factors

To evaluate the antiallergic effect of the fruit of Schizandra chinensis Baill (Family Magnoliaceae), which inhibited the mouse passive cutaneous anaphylaxis (PCA) reaction in a preliminary experiment, its main constituent, schizandrin, was isolated and its antiallergic effect investigated. Schizandrin inhibited the PCA reaction induced by the IgE-antigen complex, the scratching behaviors induced by compound 48/80 and the serum IgE production induced by ovalbumin. Schizandrin also inhibited the in vitro degranulation of compound 48/80-induced rat peritoneal mast cells and IgE-induced RBL 2H3 cells. Schizandrin reduced the protein expressions of TNF-alpha and IL-4 in IgE-induced RBL 2H3 cells. These findings suggest that schizandrin can improve IgE-induced anaphylaxis and scratching behaviors.

Topics: Animals; Anti-Allergic Agents; Cyclooctanes; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Interleukin-4; Lignans; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Molecular Structure; p-Methoxy-N-methylphenethylamine; Passive Cutaneous Anaphylaxis; Plant Extracts; Polycyclic Compounds; Pruritus; Schisandra; Tumor Necrosis Factor-alpha

To study the enzyme kinetics of schizandrin metabolism in different gender in rat liver microsomes, liver microsomes were prepared from male or female rats. Schizandrin was incubated with rat liver microsomes. Schizandrin and its metabolites were isolated and identified by HPLC-UV method. Vmax, Km and Cl(int) of schizandrin in male and female rat liver microsomes were (21.88 +/- 2.30) and (0.61 +/- 0.07) micromol x L(-1) x min(-1) x mg(-1) (protein), (389.00 +/- 46.26) and (72.64 +/- 13.61) micromol x L(-1), (0.0563 +/- 0.0007) and (0.0084 +/- 0.0008) min x mg(-1) (protein), respectively. The major metabolites of schizandrin in female and male rat liver microsomes were 7,8-dihydroxy-schizandrin (M1) and 7, 8-dihydroxy-2-demethyl schizandrin (M2b), respectively. Ketoconazole, quinidine, and orphenadrine had different level effects on schizandrin metabolism in both male and female rat liver microsomes, and cimetidine still had some inhibitory effect in male liver microsomes. CYP3A and CYP2C11 may be the main P450 enzymes in schizandrin metabolism and their difference in rat liver microsomes may be the main reason for the sex difference of metabolic enzyme kinetics and metabolites of schizandrin in rats.

Topics: Animals; Chromatography, High Pressure Liquid; Cimetidine; Cyclooctanes; Enzyme Inhibitors; Female; In Vitro Techniques; Ketoconazole; Lignans; Male; Microsomes, Liver; Orphenadrine; Plants, Medicinal; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Schisandra; Sex Factors; Spectrophotometry, Ultraviolet

To develop a method of RP-HPLC for determination of schisandrin content in Kadsura heteroclita (Roxb.) Craib.. RP-HPLC analysis was carried out by using Kromasil C18 column (5 microm, 250 mm x 4.6 mm) and methanol-water (65:35) as the mobile, and the detection wavelength was 250 nm.. The method was linear in the range of 0.08-0.06 nicrog (r = 0.9998), and the average recovery was 100.24%, with the RSD of 2.09% (n=5).. The method was simple, accurate, highly sensitive and reproducible. It may be used for the quantitative determination of schisandrin in extract of Kadsura heteroclita (Roxb.) Craib.

Topics: Chromatography, High Pressure Liquid; Cyclooctanes; Kadsura; Lignans; Plant Stems; Plants, Medicinal; Polycyclic Compounds; Quality Control; Reproducibility of Results

To study the change of schisandrin in Shengmaisan (SMS) and decomposed group.. The HPLC-UV was used to determine schisandrin in SMS and decomposed group.. To extract Schisandra chinensis with ginseng, ophiopogon, general ginsenoside or ginsenoside Rg1 could promote the content of schisandrin.. Saponin is propitious to extracting the schisandrin.

Topics: Cyclooctanes; Drug Combinations; Drug Interactions; Drugs, Chinese Herbal; Ginsenosides; Lignans; Ophiopogon; Panax; Plants, Medicinal; Polycyclic Compounds; Schisandra

Following an initial cleaning-up step on the D101 macroporous resin, a preparative high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (1:0.9:0.9:1, v/v) was used to isolate and separate schizandrin and gomisin A from Schisandra chinensis. A total of 107 mg schizandrin and 36 mg gomisin A with purities of 99.5% and 99.1% were obtained from 400 mg crude extract in one-step elution and less than 3 h, and the structure identification was performed by UV, IR, MS, 1H NMR and 13C NMR.

Topics: Chromatography, High Pressure Liquid; Countercurrent Distribution; Cyclooctanes; Dioxoles; Lignans; Polycyclic Compounds; Schisandra

A sensitive liquid chromatography-mass spectrometric (LC/MS) method for the quantification of schizandrin in rat plasma was developed and validated after solid-phase extraction (SPE). Chromatographic separation was achieved on a reversed-phase Shimadzu C(18) column with the mobile phase of acetonitrile-sodium acetate (10 micromol/L) and step gradient elution resulted in a total run time of about 11.7 min. The analytes were detected using an electrospray positive ionization mass spectrometry in the selected ion monitoring (SIM) mode. A good linear relationship was obtained in the concentration range studied (0.005-2.000 microg/mL) (r=0.9999). Lower limit of quantification (LLOQ) was 5 ng/mL and the lower limit of detection (LLOD) was 2 ng/mL using 100 microL plasma sample. Average recoveries ranged from 75.85 to 88.51% in plasma at the concentrations of 0.005, 0.100 and 1.000 microg/mL. Intra- and inter-day relative standard deviations were 5.95-12.93% and 3.87-14.53%, respectively. This method was successfully applied for the pharmacokinetic studies in rats.

Topics: Animals; Chromatography, High Pressure Liquid; Cyclooctanes; Drug Stability; Lignans; Mass Spectrometry; Polycyclic Compounds; Rats; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization

A methanolic extract of dried Schisandra fruit (Schisandra chinensis Baill.; Schisandraceae) significantly attenuated the neurotoxicity induced by L-glutamate in primary cultures of rat cortical cells. Five dibenzocyclooctadiene lignans (deoxyschisandrin, gomisin N, gomisin A, schisandrin, and wuweizisu C) were isolated from the methanolic extract; their protective effects against glutamate-induced neurotoxicity were then evaluated. Among the five lignans, deoxyschisandrin, gomisin N, and wuweizisu C significantly attenuated glutamate-induced neurotoxicity as measured by 1). an inhibition in the increase of intracellular [Ca(2+)]; 2). an improvement in the glutathione defense system, the level of glutathione, and the activity of glutathione peroxidase; and 3). an inhibition in the formation of cellular peroxide. These results suggest that dibenzocyclooctadiene lignans from Schisandra chinensis may possess therapeutic potential against oxidative neuronal damage induced by excitotoxin.

Topics: Animals; Calcium; Cells, Cultured; Cerebral Cortex; Cyclooctanes; Dioxoles; Dose-Response Relationship, Drug; Glutamic Acid; Intracellular Fluid; Lignans; Neurons; Neuroprotective Agents; Neurotoxins; Peroxides; Phytotherapy; Plant Extracts; Polycyclic Compounds; Rats; Schisandra

To optimize the combined extraction methods of Fructus Schisandrae Chinensis and Fructus Ligustri Lucidi.. The extraction effects of three processes (SFE CO2, alcohol-extraction, water-extraction) were compared by the contents of deoxyschizandrin, the dried extraction yield and production feasibility.. The method of alcohol-extraction was the best of the three methods, and the extraction conditions were optimized by orthogonal design as follows: sixfold 90% alcohol for two times and each for one hour.. The extraction method is steady and feasible, which can be used for reference for the extraction process of Fructus Schisandrae Chinensis and Fructus Ligustri Lucidi.

Topics: Alcohols; Chemistry, Pharmaceutical; Chromatography, Supercritical Fluid; Cyclooctanes; Drug Combinations; Drugs, Chinese Herbal; Fruit; Lignans; Ligustrum; Plants, Medicinal; Polycyclic Compounds; Schisandra; Technology, Pharmaceutical

Ridge Regression (RR) spectrophotometry was used in the present paper to analyse three components: deoxyschizandin, schisandrin, and gamma-schisandrin. The basic principle and the analytical steps of the approach are described in detail. The computer program of RR is based on VB language. The experimental results show that the RR method has no systematical error as compared to classical method, and the average recovery of each component is all in the range of 92.35% to 108.69%. High accuracy of RR method was obtained. Each component was determined with satisfactory results without any pre-separation. As compared with conventional methods, this method is simple, rapid and suitable for the computer-aided analysis. It was developed in statistical literature to treat these ill-conditioned systems and is an useful analytical method.

Topics: Cyclooctanes; Lignans; Polycyclic Compounds; Regression Analysis; Spectrophotometry

The 13-step synthesis of (+)-isoschizandrin reported herein features a samarium(II) iodide-promoted 8-endo ketyl-olefin coupling to assemble the eight-membered ring present in the target concomitantly with the required functionality and stereochemistry. In constructing (+)-isoschizandrin as a single atropisomer, the synthesis utilizes a kinetic resolution of a seven-membered lactone using a CBS-oxazaborolidine.

Topics: Alkenes; Aza Compounds; Boron Compounds; Cyclization; Cyclooctanes; Iodides; Ketones; Lactones; Lignans; Models, Chemical; Molecular Structure; Polycyclic Compounds; Samarium; Schisandra; Stereoisomerism

To study the chemical constituents of Bletilla striata.. Various column chromatographies with silica gel and Sephadex LH-20 were employed for the isolation and purification. The structures of the compounds were elucidated on the basis of spectral analyses and chemical methods.. Three compounds were isolated from the roots of Bletilla striata (Thunb.) Reichb. f. and identified as 5-hydroxy-4-(p-hydroxybenzyl)-3'-3-dimethoxybibenzyl (I), schizandrin (II), 4,4'-dimethoxy-(1,1'-biphenanthrene)-2,2',7,7'-tetrol (III).. Compound I is a new bibenzyl derivative and II was isolated from this plant for the first time.

Topics: Bibenzyls; Cyclooctanes; Lignans; Molecular Structure; Orchidaceae; Plant Roots; Plants, Medicinal; Polycyclic Compounds

Our previous study indicated that the water layer present in Fructus Schisandra(FS(w)) at 10 and 25 mg kg(-1)significantly counteracted cycloheximide (CXM)-induced amnesia. Therefore, the mechanism of action of the ameliorating effect of FS(w)on CXM-induced amnesia in the passive avoidance task was investigated in rats. The ameliorating effect of FS(w)on CXM-induced amnesia was depressed by scopolamine. The serotonin releaser, p -chloroamphetamine significantly antagonized the ameliorating effect of FS(w)on CXM-induced amnesia. Furthermore, the ameliorating effect was also inhibited by the 5-HT(1A)receptor agonist 8-OH-DPAT, but potentiated by the 5-HT(2)receptor antagonist ritanserin. Finally, the GABA(A)receptor antagonist bicuculline blocked the ameliorating effect of FS(w). These results suggest that the beneficial effect of FS(w)on CXM-induced amnesia is amplified by treatment with serotonergic 5-HT(2)receptor antagonists, but reduced by serotonergic 5-HT(1A)receptor agonists as well as GABA(A)and cholinergic receptor antagonists.

Topics: Administration, Oral; Amnesia; Animals; Bicuculline; Cycloheximide; Cyclooctanes; Drugs, Chinese Herbal; Lignans; Male; p-Chloroamphetamine; Phytotherapy; Plants, Medicinal; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Reaction Time; Receptors, Neurotransmitter; Ritanserin; Scopolamine; Water

Extracts from the fruits (seeds) of Schisandra chinensis L. and pure isolated substances are one of the components of medicinal preparations designed for the treatment of cardiovascular diseases, liver diseases, diseases of the CNS related to the old age, as a supplement in the treatment of neoplasms, diabetes, etc. They are also used for the production of nutraceuticals (soft drinks and health foods), preparations for oral hygiene and for the care for the skin and hair. The review discusses complex analytical methods used for the determination of the content of substances and the phenomena of population ecology in relation with drug production.

Topics: Cardiovascular Diseases; Cyclooctanes; Humans; Lignans; Plant Extracts; Plants, Medicinal; Polycyclic Compounds

A fully automated method including microbore liquid chromatography and column switching was developed for the analysis of biphenyldimethyl dicarboxylate (DDB) from human plasma samples. After direct injection of plasma samples (100 microl) into the system, deproteinization and analyte fractionation occurred on a Capcell Pak MF Ph-1 column (20x4 mm I.D.) and the DDB fraction was transferred from the MF Ph-1 column to an intermediate column (35x2 mm I.D.) using 15% acetonitrile in phosphate buffer (50 mM, pH 7.0). The main separation was performed on a microbore C18 column (150x1.5 mm I.D.) using 45% acetonitrile in water. The method showed excellent sensitivity (detection limit of 5 ng/ml) and good precision (CV.< or =3.0%), and shortened total analysis time (20 min). In the concentration range of 5-200 ng/ml, the mean recovery was 90.7+/-1.8% and the response was linear (r2> or =0.999).

Topics: Chromatography, Liquid; Cyclooctanes; Dioxoles; Hepatitis, Chronic; Humans; Lignans; Male; Plants, Medicinal; Polycyclic Compounds

[structure: see text] Studies on the synthesis of the spirocyclic cyclohexadienone ring system 2 of the schiarisanrin family of natural products 1 are described and were based on the Lewis acid-promoted C-alkylation of the corresponding phenolic precursor.

Topics: Cyclooctanes; Lignans; Plants, Medicinal; Polycyclic Compounds; Spiro Compounds

We studied the structure-activity relationships of lignans from Schisandra chinensis and their derivatives as platelet activating factor (PAF) antagonists. Strong activity was shown in lignans without an ester group at C-6, a hydroxyl group at C-7 or a methylene dioxy moiety and with an R-biphenyl configuration. 6(7)-Dehydroschisandrol A, a derivative of schisandrol A, showed the highest activity (IC50, 2.1x10(-6) M) in this study.

Topics: Biphenyl Compounds; Cyclooctanes; Esterification; Hydroxylation; Lignans; Plants, Medicinal; Platelet Activating Factor; Polycyclic Compounds; Structure-Activity Relationship

An investigation of the effect of plant matrix on the supercritical fluid extraction efficiency of five schisandrin derivatives is reported, exhibiting a great difference with respect to extraction efficiency depending on the matrix. Pure supercritical CO2 at 60 degrees C and 34.0 MPa cannot fully recover schisandrin derivatives from the leaves as much as from the other matrices. Only 36.9% of these compounds are extracted from leaves of Schisandra chinensis by supercritical CO2 in comparison with organic solvent extraction. However, more than 80% of schisandrin derivatives are obtained from both stem and fruit parts. Ethanol addition also shows a different effect depending on plant matrix; that is, CO2 modified with 10% ethanol could enhance the yield of schisandrin derivatives from leaves by four times when compared with that of pure CO2, but it has little effect on both stems and fruits.

Topics: Carbon Dioxide; Chromatography, High Pressure Liquid; Cyclooctanes; Ethanol; Fruit; Indicators and Reagents; Lignans; Plant Extracts; Plant Leaves; Plant Stems; Plants, Medicinal; Polycyclic Compounds; Solvents

To evaluate the potential activity of Schisandra chinensis in restoring hepatic drug metabolism in CCl4 damaged liver, antipyrine was employed as a probe for the possible effects of the herb on Phase I oxidative metabolism in rats. Schisandra lignan fraction (160 mg/kg) was given orally to male Sprague-Dawley rats (220-240 g) 30 min or 6 h before CCl4 intoxication (4 ml/kg, s.c.). Following a single oral dose of antipyrine (80 mg/kg) to the rats with damaged liver, the pharmacokinetics of antipyrine in whole blood were determined and levels of liver enzymes, e.g. SGPT, SGOT, and cytochrome P450 were measured. Pharmacokinetic parameters for antipyrine were estimated using noncompartmental analysis. Results indicated that CCl4 significantly increased the elimination half-life (t(1/2)) of antipyrine from 2.59 +/- 1.04 to 11.25 +/- 3.91 h (P < 0.001) and decreased its clearance (CL) from 65.94 to 10.84 ml/h as compared to control. Pretreatment with the Schisandra lignan fraction 30 min or 6 h before intoxication significantly (P < 0.001) improved antipyrine elimination by reducing its t(1/2) to 3.30 +/- 0.52 and 3.58 +/- 1.05 h, respectively. The corresponding improvements observed for CL, i.e. 49.06 +/- 21.75 ml/h (P < 0.01); 21.10 +/- 10.42 ml/h (P < 0.05), were also substantial. Moreover, normalization of SGPT, SGOT and P450 levels was observed with the two Schisandra pretreatment schedules. In conclusion, Schisandra lignans exhibited strong protective effect on Phase I oxidative metabolism in the liver damaged by CCl4. Furthermore, pretreatment of Schisandra 30 min before intoxication showed a more pronounced effect than that of the 6 h pretreatment. The current pharmacokinetic approach allowed the protective effects of Schisandra on oxidative drug metabolism in damaged liver to be systemically examined and will certainly help in the evaluation of hepato-protectants obtained from natural sources.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antipyrine; Area Under Curve; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Cyclooctanes; Fruit; Hong Kong; Lignans; Liver; Liver Diseases; Male; Medicine, Chinese Traditional; Molecular Probes; Oxidation-Reduction; Plant Extracts; Plants, Medicinal; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Seeds

To explore whether the methylenedioxy group and cyclooctadiene ring of the dibenzocyclooctadiene skeleton of schisandrins (Sch) play a role in the liver mitochondrial glutathione status enhancing activity.. The effects of three dibenzocyclooctadiene derivatives, Sch A, Sch B, Sch C, and a synthetic intermediate of Sch C, (dimethyl biphenyl dicarboxylate, DBD) on carbon tetrachloride (CCl4)-hepatotoxicity and liver mitochondrial glutathione status were examined in mice.. Pretreating mice with intragastric Sch B, Sch C, or DBD 1.mmol.kg-1.d-1 for 3 d protected against CCl4-hepatotoxicity. The hepatoprotection afforded by Sch B or Sch C pretreatment was associated with increases in liver mitochondrial reduced glutathione (mtGSH) level and glutathione reductase (mtGRD) activity, an indication of enhanced mitochondrial glutathione status. In contrast, the hepatoprotective action of DBD was not accompanied by any detectable changes in mtGSH level and mtGRD activity.. Both the methylenedioxy group and the cyclooctadiene ring of the dibenzocyclooctadiene molecule are important structural determinants in the enhancement of liver mitochondrial glutathione status.

Topics: Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Female; Glutathione; Glutathione Reductase; Lignans; Mice; Mice, Inbred BALB C; Mitochondria, Liver; Polycyclic Compounds; Structure-Activity Relationship

In this paper, schizandrin(9), the main active ingredient isolated from Schisandra chinensis, was synthesized from gallic acid by a new route. This route consists of only nine steps, including reductive-coupling reaction of compound(5) and dehydryoxylatic reaction of compound(6) to give compounds(7Z, 7E). By hydroboration, compound (8) was obtained from compound(7Z). With the presence of thallium trifluoroacetate (TTFA) and 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) compound (9) is obtained from compound (8) by intramolecular nonphenolic oxidative coupling. These compounds were identified by elemental analysis, MS, UV, IR and NMR spectra.

Topics: Cyclooctanes; Lignans; Molecular Structure; Polycyclic Compounds; Schisandra

Four extraction method for the medicinal tea Sishen Chaji, were compared with psoralen, schizandrin B and evodiamine taken as indexes. The result shows that the total contents of the three compounds decrease progressively in the following order: semi-bionic extraction, semi-bionic extraction by precipitation with alcohol, extraction with water, and extraction with water and precipitation with alcohol.

Topics: Cyclooctanes; Drug Combinations; Drugs, Chinese Herbal; Ficusin; Lignans; Plant Extracts; Polycyclic Compounds; Quinazolines; Technology, Pharmaceutical

After oral administration of schizandrin (1) to rat, the bile was collected and treated with beta-glucuronidase and arylsulfatase. Eleven metabolites, SZ-M0 (3), SZ-M1 (4), SZ-M2 (5), SZ-M3 (6), SZ-M4 (7), SZ-M5 (8), SZ-M6 (9), SZ-M7 (10), SZ-M8 (11), SZ-M9 (12) and SZ-M10 (13) were isolated from the bile treated with the enzymes. The bile after oral administration of 1 to dog was collected and treated with enzymes in the same way, and eight metabolites, 3-8, 10 and SZ-MD2 (14) were isolated from the bile treated with enzymes. The structures of these metabolites were determined on the basis of chemical and spectral studies. The major metabolite in the bile of rat was 7 and the major metabolites in the bile of dog were 7 and 14.

Topics: Animals; Bile; Cyclooctanes; Dogs; Lignans; Magnetic Resonance Spectroscopy; Male; Molecular Structure; Plants, Medicinal; Polycyclic Compounds; Rats

Schizandrin (SZ) is one of the lignan components from Schisandra fruits. A highly sensitive and precise method for the determination of SZ in human plasma was developed involving selected-ion monitoring with gas chromatography-mass spectrometry using a fused-silica capillary column. A 0.1-ml plasma sample was used for solid-phase extraction. A good linear relationship was obtained in the concentration range studied (2.0-500 ng/ml) and the method was sufficiently accurate and precise to support clinical pharmacokinetic studies. After oral administration of SZ at a dose of 15 mg to healthy male subjects, the average value of the maximum plasma concentration of SZ was 96.1 +/- 14.1 ng/ml. The plasma concentration of this substance could be monitored for 8 h after administration.

Topics: Cyclooctanes; Drug Stability; Gas Chromatography-Mass Spectrometry; Humans; Lignans; Male; Plants, Medicinal; Polycyclic Compounds; Sensitivity and Specificity

The main constituents of Radix Ginseng, Fructus Schisandrae and Radix Salviae Miltiorrhizae in Yixinfumai Granules were studied by TLC. It was found that ginsenoside got hydrolyzed while the drugs were being boiled together. The main constituents of Fructus Schisandrae were schizandrol A and B; and those of Radix Salviae Miltiorrhizae were tanshinone and protocatechuic aldehyde.

Topics: Chromatography, Thin Layer; Cyclooctanes; Dioxoles; Drug Combinations; Drugs, Chinese Herbal; Ginsenosides; Lignans; Panax; Plants, Medicinal; Polycyclic Compounds; Saponins

The metabolic transformation of schizandrin, isolated from the kernel of Schizandra chinensis Bill, was studied in vitro with phenobarbital-induced rat liver microsomal fractio containing the NADPH-generating system. The major metabolites were isolated by preparative HPLC and identified as 7,8-dihydroxy-schizandrin, 7,8-dihydroxy-2-demethyl schizandrin and 7,8-dihydroxy-3-demethyl schizandrin by UV, NMR, MS spectral analysis. The 7,8-dihydroxy-schizandrin was confirmed further by comparison with spectral and chromatographic behavior of the authentic compound. The metabolic biotransformation of schizandrin in vivo was also determined.

Topics: Animals; Biotransformation; Chromatography, High Pressure Liquid; Cyclooctanes; Lignans; Male; Microsomes, Liver; Polycyclic Compounds; Rats

Schizandrol A (2',3',4',1",2",3"-hexamethoxy-6, 7-dimethyl-1,2,3,4-dibenzo-1,3-cyclooctadien-6-ol) is one of the effective components in the dried fruit of Schizandra chinensis Bail. Previous studies have found that schizandrol A exerts inhibitory effects on the central nervous system (CNS). For the purpose of elucidating the mechanism of inhibition, the concentrations of monoamine neurotransmitters and their metabolites in rat brain and the effects of schizandrol A on some receptors were determined by the ion-pairing reversed-phase liquid chromatography with electrochemical detection method and competitive binding assay. In the neurotransmitter studies, significant elevations of dopamine and its metabolite DOPAC (in striatum) and DA (in hypothalamus) were observed after i.p. administration of 50 mg/kg or 100 mg/kg of schizandrol A. But the receptor binding experiments showed that schizandrol A had no affinity for dopamine D1 and D2 receptors. Serotonin receptors and alpha 1-,alpha 2-adrenergic receptors, and it did not affect the binding of dopamine to dopamine D1 or D2 receptors. These results indicate that the inhibition exerted by schizandrol A on the CNS may be related to the dopamine system, and the increase of dopamine turnover has nothing to do with dopamine receptors. The concentrations of the norepinephrine metabolite MHPG and the serotonin metabolite 5-HIAA showed changes in rat striatum and hypothalamus after schizandrol A treatment, but norepinephrine and serotonin levels were unaffected.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Biogenic Monoamines; Brain; Corpus Striatum; Cyclooctanes; Dopamine; Hypothalamus; Lignans; Male; Neurotransmitter Agents; Polycyclic Compounds; Rats; Rats, Inbred Strains; Receptors, Dopamine

Topics: Animals; Cardiovascular Agents; Cyclooctanes; Doxorubicin; Drugs, Chinese Herbal; Free Radical Scavengers; Leukemia P388; Lignans; Malondialdehyde; Mitochondria, Heart; Phenanthrenes; Polycyclic Compounds

The reactive oxygen radicals produced from human polymorphonuclear leukocytes (PMN) stimulated with PMA (phorbol myristate acetate), hydroxyl radicals generated by a Fenton reaction, and superoxide anion radicals produced by irradiating solutions of riboflavin in the presence of EDTA have been taken as the models for production of oxygen radicals. With the use of the electron spin resonance spin trapping method, the scavenging effects of schizandrol A (solA) (5 x 10(-4) M) and schizandrin B (sinB) (5 x 10(-4) M) have been studied and compared with the effects of vitamin E (5 x 10(-4) M) and vitamin C (5 x 10(-4) M). It has been found that in cell system the scavenging effects of sinB and solA, as judged by ESR spin trappings, on hydrpxyl radicals (.OH) are greater than vitamin E and vitamin C and the scavenging effects on superoxide anion (O2) are greater than vitamin E but lower than vitamin C. With respect to the Fenton reaction, sinB has the strogest scavenging effect on .OH (77%) and solA has strong scavenging effect on .OH (63%), both of them larger than that of vitamin E (35%) and vitamin C (56%). In the riboflavin/EDTA system, the scavenging effect of sinB (46%) is smaller than that of vitamin C (96%) but larger than that of vitamin E (23%); the scavenging effect of solA is not obvious (14%). With the use of spin probe oximetry, the oxygen consumption during the respiratory burst of stimulated PMN has been measured when exposed to schizandrins. The experiment results demonstrated that they do not affect the activity of production of active oxygen radicals in the respiratory burst of PMN stimulated with PMA.

Topics: Cyclooctanes; Drugs, Chinese Herbal; Electron Spin Resonance Spectroscopy; Free Radicals; Humans; In Vitro Techniques; Lignans; Lymphocyte Activation; Molecular Structure; Neutrophils; Oximetry; Oxygen Consumption; Polycyclic Compounds; Tetradecanoylphorbol Acetate

We have studied the scavenging effects of different structures and configurations of schizandrins isolated from Fructus Schizandrae, a traditional Chinese herb, on active oxygen radicals with the method of spin-trapping technique. The active oxygen radicals were produced from human polymorphonuclear leukocytes (PMN) stimulated with phorbol myristate acetate (PMA). In addition, the scavenging effects of schizandrins on hydroxyl radicals (.OH) in Fenton's reaction and the scavenging effects on superoxide anions (O2-.) in both riboflavin/EDTA and xanthine/xanthine oxidase systems have also been studied. They are compared with the scavenging effects of both Vitamin C (Vc) and Vitamin E (VE). The experimental results have shown that the scavenging effect of schizandrin B (Sin B) on the active oxygen radicals is stronger than that of S(-) Sin B and R(+) Sin B. For schizandrins of the same molecular structures with different stereoconfigurations the scavenging effects of S type of the benzene ring on active oxygen radicals are stronger than those of R type and for schizandrins of the same stereoconfigurations with different structures the scavenging effects of schizandrin C (Sin C) on the active oxygen radicals are stronger than those of Sin B.

Topics: Cyclooctanes; Drugs, Chinese Herbal; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Humans; Hydroxides; Hydroxyl Radical; Lignans; Neutrophils; Oxygen Consumption; Plants, Medicinal; Polycyclic Compounds; Superoxides

A method of TLC densitometry was developed to determine the active ingredients (Wuweizisu A, B, C; Wuweizichun A, B; Wuweizi ester and schisanhenol) in Schisandra kernels. The samples were extracted with hexane (3 X 5 ml) for 8, 4 and 4 h respectively. The hexane extract was evaporated to dryness and then dissolved in 1 ml of methanol. Standard solutions and sample solutions were spotted on a silica gel GF254 plate, and developed with toluene-ethyl acetate (9:1) for 18 cm (for Wuweizisu A, B, C) and with toluene-ethyl acetate (4:6) for 18 cm (for Wuweizichun A, B, Wuweizi ester and schisanhenol). On examining the chromatogram under UV light the ingredients appeared as dark spots. A Shimadzu TLC model 910 was used for scanning at lambda s 260 nm and lambda R 350 nm by reflection mode. Linear calibration curves were obtained for the 7 constituents in the range of 1-5 micrograms. The average recoveries of the 7 constituents were 92.4-101.6%; the variation coefficients were 1.62-5.28%. The spots were stable for more than 24 h. This method is sufficiently simple, rapid and accurate for routine analysis.

Topics: Chromatography, Thin Layer; Cyclooctanes; Densitometry; Dioxoles; Drugs, Chinese Herbal; Lignans; Polycyclic Compounds

Fructus Schizandrae (FS) is a well-known Chinese herb which has been widely used in ancient China. During recent decades, it has been found to be effective in viral and chemical induced hepatitis. In this paper, we report the studies on the chemical constituents and pharmacological actions of FS on mice liver. The results indicated that FS and its several components can mainly protect liver from injury induced by toxic substances such as CCl4; they have anti-oxidant activities against oxygen free radicals; FS and four components have inducing action on liver cytochrome P-450; they also promote certain anabolic metabolism such as serum protein biosynthesis and glycogenesis. All these activities would be of importance in the protection and repair of the injured liver cells. The clinical use of FS is also presented.

Topics: Animals; Chemical and Drug Induced Liver Injury; Cyclooctanes; Cytochrome P-450 Enzyme System; Dioxoles; Drugs, Chinese Herbal; Hepatitis B; Humans; Lignans; Lipid Peroxidation; Mice; Microsomes, Liver; Polycyclic Compounds; Rats

Topics: Acetates; Biological Availability; Cyclooctanes; Hot Temperature; Lignans; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Oils, Volatile; Plants, Medicinal; Polycyclic Compounds

Topics: Animals; Cyclooctanes; Cytochrome P-450 Enzyme System; Enzyme Induction; Lignans; Male; Mice; Microsomes, Liver; Oxygenases; Polycyclic Compounds; Rats; Rats, Inbred Strains

Topics: Animals; Antibody Formation; Cortisone; Cyclooctanes; Female; Immunosuppressive Agents; Lignans; Male; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Mice; Plants, Medicinal; Polycyclic Compounds; Rosette Formation

Topics: Animals; Cyclic AMP; Cyclooctanes; Emulsions; Lignans; Liver; Mice; Polycyclic Compounds

Topics: Animals; Antibody-Producing Cells; Cyclooctanes; Dose-Response Relationship, Drug; Female; Immunosuppressive Agents; Lignans; Male; Mice; Polycyclic Compounds; Rosette Formation

Topics: Animals; Brain; Chromatography, Thin Layer; Cyclooctanes; Kinetics; Lignans; Male; Mice; Polycyclic Compounds; Rats

Topics: Aggression; Animals; Anticonvulsants; Brain; Catalepsy; Cyclooctanes; Humans; Lignans; Male; Mice; Motor Activity; Polycyclic Compounds; Rats; Sleep

Seven compounds isolated from Fructus Schizandrae chinensis, a traditional Chinese tonic, which is also able to increase liver lesions by hepatoxic chemicals, are named Schizandrin (Sin) A, B and C, Schizandrol (Sol) A and B and Schizandrer (Ser) A and B. They are dibenzo[a,c]cyclooctene derivatives. Dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxy-biphenyl-2,2'-dicarboxylate (DDB) is an intermediate for synthesizing Sin C. The interactions of these compounds with rat liver microsomes in vitro have been investigated. Sol A and Sol B gave type I difference spectrum, the other six compounds gave 'reverse type I' difference spectrum. When Schizandrins or DDB were incubated with NADPH-reduced microsomes, Sin B, Sin C, Sol B, Ser A and Ser B generated dual Soret peaks of 455--460 nm and 425--430 nm, the other three compounds caused a difference spectrum without 455 nm peak. All these compounds more or less inhibit liver microsomal hydroxylation of benzo[a]pyrene (BP) demethylation of aminopyrine. Sin B, Sol B and DDB decreased mutagenicity of BP in Ames test.

Topics: Animals; Aryl Hydrocarbon Hydroxylases; Cyclooctanes; Cytochrome P-450 Enzyme System; Dioxoles; In Vitro Techniques; Lignans; Male; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Microsomes, Liver; Mutagens; NADP; Oxidation-Reduction; Plants, Medicinal; Polycyclic Compounds; Rats; Rats, Inbred Strains

Fructus Schizandrae, a traditional Chinese tonic, has been shown to lower the elevated serum glutamic pyruvic transaminase (SGPT) levels of patients with chronic viral hepatitis and several of its components decrease the hepatotoxicity of carbon tetrachloride (CCl4) in animals. This paper deals with the mechanism of protection against CCl4-hepatotoxicity of these compounds as well as of DDB, a synthetic analogue of Schizandrin (Sin) C. Of the seven components, Sin B and C, Schizandrol (Sol) B, Schizandrer (Ser) A and B, as well as dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxy-biphenyl-2,2'-dicarboxylate (DDB) were shown to inhibit CCl4-induced lipid peroxidation and [14C]Cl4 covalent binding to lipids of liver microsomes from phenobarbital(PB)-treated mice. The compounds also decreased carbon monoxide (CO) production and cofactor (NADPH, oxygen) utilization during CCl4 metabolization by liver microsomes. It may be postulated, therefore, that the hepatoprotective effect of certain components isolated from Fructus Schizandrae as well as DDB is due to their inhibitory effect on CCl4-induced lipid peroxidation and the binding of CCl4-metabolites to lipids of liver microsomes.

Topics: Animals; Carbon Tetrachloride; China; Cyclooctanes; Dioxoles; Lignans; Lipid Metabolism; Lipid Peroxides; Male; Mice; Mice, Inbred DBA; Microsomes, Liver; NADP; Oxygen Consumption; Plants, Medicinal; Polycyclic Compounds

Topics: Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cyclooctanes; Cycloparaffins; Drug Evaluation, Preclinical; Lignans; Liver Diseases; Male; Plant Extracts; Plants, Medicinal; Polycyclic Compounds; Rats; Rats, Inbred Strains

Topics: Animals; Cyclooctanes; Cytochrome P-450 Enzyme System; Dioxolanes; Dioxoles; Hydrocarbons, Chlorinated; Immunodiffusion; Lignans; Male; Microsomes, Liver; Phenobarbital; Polycyclic Compounds; Rats; Rats, Inbred Strains

Topics: Alanine Transaminase; Animals; Cyclooctanes; Hepatitis, Viral, Human; Lignans; Mice; Polycyclic Compounds; Structure-Activity Relationship

Topics: Animals; Cyclooctanes; Cycloparaffins; Dioxoles; Drug Synergism; Guinea Pigs; Hexobarbital; Lignans; Male; Methamphetamine; Mice; Motor Activity; Plant Extracts; Plants, Medicinal; Polycyclic Compounds; Rats; Rats, Inbred Strains; Sleep

Topics: Chemical Phenomena; Chemistry; Cyclooctanes; Cycloparaffins; Dioxoles; Lignans; Molecular Conformation; Plant Extracts; Plants, Medicinal; Polycyclic Compounds

Topics: Cyclooctanes; Humans; Lignans; Muscles; Polycyclic Compounds; Schisandra