lignans and schisanhenol

Liver fibrosis is a pathological manifestation induced by chronic liver injury and may cause cirrhosis and liver cancer with the chronic progression of fibrosis. During the onset and progression of liver fibrosis, the activation of hepatic stellate cells (HSCs) is the core mechanism for the secretion of many extracellular matrices to induce fibrosis. Lignans are reportedly the main effective components of Schisandra chinensis with good anti-fibrosis effects. In this study, we compared the inhibiting effects of the seven lignan components from S. chinensis on HSC activation. We found that the seven lignans inhibited the activation of human HSCs (LX-2) in various degrees. Among all lignans, schisanhenol showed the best effect in inhibiting the activation of LX-2 with a dose-effect relationship. Sal also inhibited the phosphorylations of Smad1, Smad2, Smad3, extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and nuclear transcription factor-κB (NF-κB), as well as downregulated Smad4. All these findings suggested that schisanhenol may ameliorate liver fibrosis by inhibiting the transforming growth factor β (TGF-β)/Smad and mitogen-activated protein kinase (MAPK) signaling pathways. Remarkably, schisanhenol may be a potential anti-liver fibrosis drug and warrants further research.

Topics: Cell Line; Cyclooctanes; Fruit; Hepatic Stellate Cells; Humans; JNK Mitogen-Activated Protein Kinases; Lignans; Liver Cirrhosis; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Polycyclic Compounds; Schisandra; Signal Transduction; Smad1 Protein; Smad2 Protein; Smad3 Protein; Transforming Growth Factor beta

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Topics: Carboxylesterase; Carboxylic Ester Hydrolases; Cyclooctanes; Dioxoles; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Interactions; Enzyme Inhibitors; Humans; Lignans; Microsomes, Liver; Molecular Docking Simulation; 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

Schisanhenol (Sol) was isolated from Schisandra rubriflora, and a series of derivatives (1-16, 15a-16a, and 15b-16b) were designed and prepared by chemical modification. The curative and protective effects of these dibenzocyclooctadiene lignan analogues against tobacco mosaic virus (TMV) were evaluated. Most analogues exhibited stronger protective effects than the positive control ningnanmycin. Dibromoschisanhenol (6) at 0.25mM exhibited the strongest protective activity (83.5±1.8% at 0.25mM), and 14-(3, 5-dibenzyloxy)-benzoyloxyschisanhenol (16) showed a significant curative effect (78.0±3.8% at 0.15mM) that was much stronger than that of the commercial virucide ningnanmycin. This study is the first to demonstrate that natural dibenzocyclooctadiene lignans and analogues are active against plant viruses.

Topics: Antiviral Agents; Cyclooctanes; Lignans; Molecular Structure; Polycyclic Compounds; Structure-Activity Relationship; Tobacco Mosaic Virus

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

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

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

To investigate the effect of schisanhenol (Sal) on copper ion-induced oxidative modulation of human low density lipoprotein (LDL).. The antioxidative activity of eight schisandrins (DCL) on microsome lipid peroxidation induced by Vit C/NADPH system was first observed, and then, the effect of Sal on Cu2+-induced human LDL oxidation was studied. The generation of malondialdehyde (MDA), lipofuscin, reactive oxygen species (ROS), consumption of a-tocopherol as well as electrophoretic mobility of LDL were determined as criteria of LDL oxidation. Finally, the quantum chemical method was used to calculate the theoretical parameters of eight DCL for elucidating the difference of their antioxidant ability.. Sal was shown to be the most active one among eight schizandrins in inhibiting microsome lipid oxidation induced by Vit C/NADPH. Sal 100, 50, and 10 micromol/L inhibited production of MDA, lipofuscin and ROS as well as the consumption of a-tocopherol in Cu2+-induced oxidation of human LDL in a dose-dependent manner. Sal also reduced electrophoretic mobility of the oxidized human LDL. Further study of quantum chemistry found that Sal was the strongest one among eight DCL to scavenge O2, R, RO and ROO radicals.. Sal has antioxidative effect on human LDL oxidation. The mechanism of Sal against LDL oxidation may be through scavenging free radicals.

Topics: alpha-Tocopherol; Animals; Antioxidants; Copper; Cyclooctanes; Drugs, Chinese Herbal; Free Radical Scavengers; Humans; Lignans; Lipid Peroxidation; Lipofuscin; Lipoproteins, LDL; Male; Malondialdehyde; Microsomes, Liver; Oxidation-Reduction; Polycyclic Compounds; Rats; Rats, Wistar; Reactive Oxygen Species

The anti-oxidant activity of nine dibenzocyclooctene lignans isolated from Schisandra chinensis, S. rubriflora, and Kadsura longipedunculata, respectively, was studied. Seven of the 9 lignans (1 mM) inhibited iron/cysteine-induced lipid peroxidation (malondialdehyde, MDA, formation) of rat liver microsomes as well as superoxide anion production in the xanthine/xanthine oxidase system. The actions of the 7 lignans were much more potent than vitamin E at the same concentration of 1 mM. Among the lignans, schisanhenol was the most active one. This compound also prevented the decrease of membrane fluidity of liver microsomes induced by iron/cysteine. The results indicated that seven of the lignans such as schisanhenol have anti-oxidant activities.

Topics: Animals; Antioxidants; Cyclooctanes; Drugs, Chinese Herbal; Humans; Lignans; Lignin; Lipid Peroxidation; Male; Microsomes, Liver; Polycyclic Compounds; Rats; Rats, Wistar

The effects of two dibenzocyclooctene lignans on peroxidative damage of aging and ischemic rat brain were studied. Incubation of eight-month-old rat brain mitochondria and membrane suspension with Fe(2+)-cysteine resulted in the formation of malondialdehyde (MDA) and decrease of ATPase activity. Schisanhenol (Sal) (10(-4) M) completely inhibited the peroxidative damages of brain mitochondria and membrane of rats. The swelling and disintegration of brain mitochondria, as well as the reduction of brain membrane fluidity induced by Fe(2+)-cysteine were also prevented by Sal. The results of imitative experiment of ischemia and reperfusion of brain mitochondria and membrane in vitro indicated that Sal significantly impeded production of MDA and loss of ATPase activity induced by reoxygenation following anoxia. Oral administration of Sal induced increase of cytosol glutathione-peroxidase of brain in mice under the condition of reoxygenation following anoxia. The other compound schizandrin (Sin B) also has similar activity. But its potency is weaker than that of Sal. All these results indicate that Sal and Sin B have protective action against oxidative stress.

Topics: Adenosine Triphosphatases; Aging; Animals; Antioxidants; Brain; Brain Ischemia; Cyclooctanes; Drugs, Chinese Herbal; Free Radicals; Lignans; Lipid Peroxidation; Male; Mitochondrial Swelling; Polycyclic Compounds; Rats; Rats, Inbred Strains; Vitamin E

The effect of nine dibenzo[a,c]cyclooctene lignans isolated from Fructus schizandrae on in vitro and in vivo lipid peroxidation of liver microsomes as well as on anti-oxidative enzyme activities were studied. Seven of the nine lignans (1 mM) were shown to inhibit Vit C/NADPH induced lipid peroxidation (malondialdehyde (MDA) formation) of rat liver microsomes. Of these compounds, schisanhenol (Sal), S(-)schizandrin C (S(-)sin C) and S(-)schizandrin B (S(-)sin B) were shown to be more potent than Vit E at the same concentration. Sal and Sin B were able to inhibit gossypol-induced superoxide anion generation in rat liver microsomes. In addition, oral administration of Sal and Sin B markedly reduced liver MDA formation induced by ethanol, 15 ml/kg in mice, and increased superoxide dismutase and catalase activities in rat liver cytosol. The data of this paper are in favor of the conclusion that some lignans, like Sal, have strong anti-oxidant activity. The mechanisms of anti-oxidant activity of the lignans were discussed.

Topics: Animals; Catalase; Cyclooctanes; Cytosol; Ethanol; Gossypol; Lignans; Lignin; Lipid Peroxidation; Liver; Male; Malondialdehyde; Microsomes, Liver; NAD; Oxidation-Reduction; Plants, Medicinal; Polycyclic Compounds; Rats; Rats, Inbred Strains; Superoxide Dismutase; Superoxides

It was reported that Schisanhenol (Sal) isolated from Schisandrae Rubriflora inhibited lipid peroxidation induced by ferrous-cysteine and NADPH-ascorbic acid. In this studies the oxygen radical scavenging activity of Sal was detected by electron spin resonance (ESR) and spin trapping. Sal was shown to scavenge oxygen radicals produced by human neutrophils (Neu) stimulated by tetradecanoylphorbol acetate (TDPA). But no effect of Sal was seen on oxygen consumption measured by spin label oximetry in Neu during respiratory burst. In Fenton reaction system, the inhibitory rate of hydroxyl radical by Sal was 34.4%. In xanthine-xanthine oxidase and uv-irradiation of riboflavin systems, Sal scavenged superoxide anion radical by 26.1% and 21.9%, respectively. In all these systems the action of Sal was more potent than that of vitamin E. It may be concluded that Sal possesses a free radical-scavenging activity.

Topics: Cyclooctanes; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Free Radicals; Humans; Lignans; Neutrophils; Oxygen; Polycyclic Compounds

Intragastric gavage of schizandrin B (Sin B) and schisanhenol (Sal) 200 mg/kg once daily for 3 d significantly increased liver glutathione-S-transferase (GSH-S-T) and microsomal cytochrome P-450 in mice and rats. Sin B and Sal antagonized the increase of uterus weight induced by sc estradiol in ovariectomized, and decreased serum estradiol level in mice. RIA and HPLC showed an enhancement in [3H] estradiol metabolism by liver microsomes from Sin B- and Sal-treated mice. The results indicated that both Sin B and Sal have inductive actions on drug metabolizing-phase I and phase II enzymes in mice and rats.

Topics: Animals; Cyclooctanes; Cytochrome P-450 Enzyme System; Estradiol; Female; Glutathione Transferase; Lignans; Liver; Male; Mice; Microsomes, Liver; Polycyclic Compounds; Rats; Rats, Inbred Strains

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