benzofurans and tanshinone

The article reviewed the research on the pharmacological effects of Danshen on hemorheology. We discussed the action mechanism of Danshen and its preparations from the points of hemorheology, blood and vessel endothelium cell. Danshen and its preparations can obviously improve the hemorheological characteristic by various ways.

Topics: Abietanes; Animals; Benzofurans; Drugs, Chinese Herbal; Hemorheology; Hemostasis; Lactates; Phenanthrenes; Plant Roots; Plants, Medicinal; Platelet Aggregation; Salvia miltiorrhiza

Danshen, the dried root of Salvia miltiorrhiza, has been widely used in China and, to a lesser extent, in Japan, the United States, and other European countries for the treatment of cardiovascular and cerebrovascular diseases. In China, the specific clinical use is angina pectoris, hyperlipidemia, and acute ischemic stroke. The current review covers its traditional uses, chemical constituents, pharmacological activities, pharmacokinetics, clinical applications, and potential herb-drug interactions based on information obtained in both the English and Chinese literature. Although numerous clinical trials have demonstrated that certain Danshen products in China are effective and safe for the treatment of cardiovascular diseases, most of these lack sufficient quality. Therefore, large randomized clinical trials and further scientific research to determine its mechanism of actions will be necessary to ensure the safety, effectiveness, and better understanding of its action.

Topics: Abietanes; Angina Pectoris; Animals; Benzofurans; Drugs, Chinese Herbal; Fibrinolytic Agents; Herb-Drug Interactions; Humans; Hyperlipidemias; Lactates; Phenanthrenes; Phenanthrolines; Plant Extracts; Randomized Controlled Trials as Topic; Salvia miltiorrhiza; Stroke

Salvianolic acid B(Sal B), tanshinone Ⅱ_A(TSN Ⅱ_A), and glycyrrhetinic acid(GA) lipid emulsion(GTS-LE) was prepared by the high-speed dispersion method combined with ultrasonic emulsification.The preparation process of the emulsion was optimized by single-factor method and D-optimal method with appearance, centrifugal stability, and particle size of the emulsion as evalua-tion indexes, followed by verification.In vitro release of Sal B, TSN Ⅱ_A, and GA in GTS-LE was performed by reverse dialysis.In vivo pharmacokinetic evaluation was carried out in mice.The acute liver injury model was induced by acetaminophen.The effect of oral GTS-LE on the acute liver injury was investigated by serum liver function indexes and pathological changes in liver tissues of mice.The results showed that under the optimal preparation process, the average particle size of GTS-LE was(145.4±9.25) nm and the Zeta potential was(-33.6±1.45) mV.The drug-loading efficiencies of Sal B, TSN Ⅱ_A, and GA in GTS-LE were above 95%, and the drug release in vitro conformed to the Higuchi equation.The pharmacokinetic results showed that the C_(max) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.128, 2.7, and 2.85 times that of the GTS-S group, and AUC_(0-t) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.09, 2.23, and 1.9 times that of the GTS-S group.After intragastric administration of GTS-LE, the activities of alanine aminotransferase and aspartate aminotransferase were significantly inhibited, the content of malondialdehyde was reduced, and the structure of hepatocytes recovered to normal.In conclusion, GTS-LE can delay the release of Sal B and promote the release of TSN Ⅱ_A and GA.The encapsulation of three drug components in the emulsion can improve the oral bioavailability to varying degrees and can effectively prevent the acute liver injury caused by acetaminophen.

Topics: Abietanes; Acetaminophen; Alanine Transaminase; Animals; Antipyretics; Aspartate Aminotransferases; Benzofurans; Chemical and Drug Induced Liver Injury; Depsides; Emulsions; Glycyrrhetinic Acid; Liver; Malondialdehyde; Mice

In this work, a smartphone-based device was constructed for thin-layer chromatography (TLC) detection and semi-quantitative analysis of the components of Salvia miltiorrhiza. The key construction and shooting parameters were investigated by the relative peak area and signal-to-noise ratio. The best conditions were as follows: shooting height, 17 cm; angle between the UV lamp and TLC plate, 58°; exposure compensation, 0~0.2 EV; and shutter speed under daylight and UV 365 nm, 1/50 s and 1/5 s, respectively. These ideal conditions could be replicated by smartphones from different brands with different versions of software. With good precision, repeatability and stability, the developed device was used for the semi-quantitative analysis of salvianolic acid B, rosmarinic acid, cryptotanshinone, tanshinone I, tanshinone IIA, and miltirone in the TLC analysis of 10 batches of S. miltiorrhiza. The results were compared with those obtained by a TLC densitometric scanner and two common types of image processing software, i.e., Gelanalyzer and ImageJ. Except for salvianolic acid B in the TLC densitometric scanner, all results were not significantly different among these methods, which suggested that smartphones might be a useful tool for the quality control of traditional Chinese medicines.

Topics: Abietanes; Benzofurans; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Cinnamates; Depsides; Drugs, Chinese Herbal; Phenanthrenes; Quality Control; Rosmarinic Acid; Salvia miltiorrhiza; Smartphone

Autophagy plays an important role in cellular homeostasis. Oxidative stress stimulated endothelial excessive autophagy has been proposed as a major risk factor for cardiovascular diseases (CVD). Danhong injection (DHI), the most prescribed traditional Chinese medicine for the treatment of CVD, has been shown to elicit vascular protective effects. However, its underlying mechanisms remain poorly defined. This study aimed to uncover the protective effects of DHI and its main bioactive components on autophagy injury of human umbilical vein endothelial cells (HUVECs) induced by H. HUVECs were treated with different concentrations of DHI or its components, after exposed to H. DHI and its components all had anti-autophagy effects. And Sal B (0.5 μg/ml) inhibited HUVECs autophagy via miR-19a/SIRT1 pathway.

Topics: Abietanes; Apoptosis; Autophagy; Beclin-1; Benzofurans; Drugs, Chinese Herbal; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Peroxide; MicroRNAs; Oxidative Stress; Sirtuin 1

Fufang Danshen preparation (FDP) is consisted of Salviae Miltiorrhizar Radix et Rhizoma (Danshen), Notoginseng Radix et Rhizoma (Sanqi) and Borneolum Syntheticum (borneol). FDP is usually used to treat myocardial ischemia hypoxia, cerebral ischemia and alzheimer's disease, etc. In the treatment of cerebrovascular diseases, borneol is usually used to promote the absorption and distribution of the bioactive components to proper organs, especially to the brain. The purpose of this study is investigating the effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA (TS IIA), salvianolic acid B (SAB) and ginsenoside Rg1 in FDP. Male healthy Sprague-Dawley (SD) rats were given Danshen extracts, Sanqi extracts (Panax notoginsengsaponins) or simultaneously administered Danshenextracts, Sanqi extracts and borneol. Plasma and brain samples were collected at different points in time. The concentration of TS IIA, SAB and Rg1 was determined by UPLC-MS/MS method. The main pharmacokinetics parameters of plasma and brain tissue were calculated by using Phoenix WinNolin 6.1 software. In comparison with Danshen and Sanqi alone, there were significant differences in pharmacokinetic parameters of TS IIA, SAB and Rg1, and the brain distribution of SAB and TS IIA when Danshen, Sanqi and borneol were administrated together. Borneol statistically significant shortened t

Topics: Abietanes; Animals; Benzofurans; Brain; Camphanes; Chromatography, Liquid; Drugs, Chinese Herbal; Ginsenosides; Male; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

Many Chinese herbs are well known for their neuroprotective and anti-oxidant properties. Extracts of Salvia miltiorrhiza and Anemarrhenae asphodeloides, tanshinone IIA (tanIIA), salvianolic acid B (Sal B) and sarsasapogenin (ML-1), were selected to study their dissociation potential towards Aβ

Topics: Abietanes; Alzheimer Disease; Amyloid beta-Peptides; Anemarrhena; Benzofurans; Cell Line; China; Humans; Neuroprotective Agents; Peptide Fragments; Plant Extracts; Salvia miltiorrhiza; Spirostans

The purpose of this study is to reveal the impact of the plant hormone salicylic acid (SA) and methyl jasmonate (MeJA) on the growth, effective components accumulation, and related gene expression of the hairy root of Salvia przewalskii Maxim. Various concentrations of SA (0, 25, 50, 100, 200 μM) or MeJA (0, 50, 100, 200, 400, 600 μM) were added to the culture medium of Salvia przewalskii Maxim. Low concentrations of SA promoted the growth of hairy root, while a high concentration inhibited it. 0 to 400 μM MeJA promoted the growth of hairy root, but 600 μM MeJA starts to inhibit its growth. 50 μM SA and 400 μM MeJA significantly enhanced the production of caffeic acid, rosmarinic acid, salvianolic acid B, cryptotanshinone, and tanshinone IIA. In general, 50 μM SA can be used to accumulate of tanshinone in hairy roots of S. przewalskii with 6 days. 400 μM MeJA can be used to accumulate of phenolic acids in hairy roots of S. przewalskii with 3 days. The selected genes in the tanshinone and phenolic acid biosynthetic pathway were upregulated with elicitation. To obtain a higher yield and content of secondary metabolites, it is advisable to use 50 μM SA or 400 μM MeJA as the optimal doses to cultivate the hairy root of S. przewalskii. This study provides, for the first time, an efficient tanshinone and phenolic acid production method for S. przewalskii.

Topics: Abietanes; Acetates; Benzofurans; Caffeic Acids; Cinnamates; Cyclopentanes; Depsides; Dose-Response Relationship, Drug; Gene Expression Regulation, Plant; Hydroxybenzoates; Oxylipins; Phenanthrenes; Plant Growth Regulators; Plant Proteins; Plant Roots; Rosmarinic Acid; Salicylic Acid; Salvia; Time Factors

Danshen is a first-line traditional Chinese medicine derived from Salvia miltiorrhiza Bunge consisting mainly of tanshinone IIA, tanshinol, protocatechuic aldehyde, and salvianolic acid B, it is widely used to treat cardiovascular diseases based on the synergistic effect of its multiple active components. Recent studies have indicated that the overall effect of traditional Chinese medicine is closely related to the in vivo coexistence of a variety of active components.. The prolongation of the coexistence of the four active components in Danshen in vivo by regulating their pharmacokinetic processes may contribute to better efficiency.. Individual sustained-release pellets of the four main active components in Danshen were respectively prepared according to the optimised formulations developed in our previous studies to modulate their in vivo processes, in which the desired release profiles of each kind of sustained-release pellets for formulation optimisation were calculated based on the point-area deconvolution and circadian rhythm of variant angina. The four kinds of sustained-release pellets were filled into capsules on the basis of the original weight ratio of the four active components in purified Salvia miltiorrhiza extract for further in vitro release and pharmacokinetic and pharmacodynamic investigations.. The release behaviours of the combined Danshen capsules composed of the four kinds of sustained-release pellets were evaluated in three media with different pH levels (pH 1.2, 6.8, and pure water). The release profiles of each kind of sustained-release pellets in pH 6.8 PBS and pH 1.2 HCl were similar to the release profile of those in pure water (similarity factors f. Sustained-release preparations can markedly prolong the in vivo coexistence of multiple components in Danshen to enhance their overall effects, which provides a potent strategy for developing the combination therapy of traditional Chinese medicine.

Topics: Abietanes; Benzaldehydes; Benzofurans; Caffeic Acids; Capsules; Cardiovascular Diseases; Catechols; Delayed-Action Preparations; Drugs, Chinese Herbal; Humans; Hydrogen-Ion Concentration; Medicine, Chinese Traditional; Salvia miltiorrhiza

The effect of light-emitting diodes (LEDs) on the production of secondary metabolites in medicinal plants and hairy roots is receiving much attention. The roots and rhizomes of the traditional Chinese medicinal plant Salvia miltiorrhiza Bunge are widely used for treating cardiovascular and cerebrovascular diseases. The main components are liposoluble tanshinones and hydrophilic phenolic acids. Moreover, hairy root culture of S. miltiorrhiza has been used in research of valuable plant-derived secondary metabolites. In this study, we examined the effect of LEDs with different combinations of wavelengths on the content of the main components in hairy roots of S. miltiorrhiza. Tanshinone IIA (TSIIA) content in hairy roots was significantly decreased with all light treatments containing blue light by >60% and was 9 times lower with LED treatment duration changed from 1 week to 3 weeks. HMGR, DXS2, DXR, GGPPS, CPS and CYP76AH1 genes involved in the tanshinone biosynthesis pathway were downregulated by blue light. Furthermore, light quality treatments have different effect on the accumulation of phenolic acids in hairy roots of S. miltiorrhiza. The light treatments 6R3B, 6B3IR, 7RGB and 2R6BUV for 3 weeks could increase rosmarinic acid (RA) content slightly but not salvianolic acid B (SAB) content. Different secondary metabolite contents could be regulated by different wavelength combinations of LEDs. Blue light could reduce TSIIA content in hairy roots of S. miltiorrhiza via gene regulation.

Topics: Abietanes; Alkyl and Aryl Transferases; Benzofurans; Biomass; Chromatography, High Pressure Liquid; Farnesyltranstransferase; Gene Expression Regulation, Plant; Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; Light; Plant Proteins; Plant Roots; Salvia miltiorrhiza

A sensitive and specific ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed for analysis of tanshinone ⅡA(TSⅡA), salvianolic acid B(SAB) and ginsenoside Rg₁ (GRg₁) in rat plasma and brain tissues. Male healthy Sprague-Dawley(SD) rats were orally given single dose of Fufang Danshen preparation (TS ⅡA 60 mg•kg⁻¹, SAB 300 mg•kg⁻¹, GRg₁ 150 mg•kg⁻¹, borneol 300 mg•kg⁻¹), and their blood samples and brain tissues were collected at different time points. The drug plasma and brain tissue concentrations of the three analytes were determined by UPLC-MS/MS method. Subsequently, the main pharmacokinetics parameters of plasma and brain tissues were calculated by using Phoenix WinNolin 6.1 software. The methodological test showed that all of analytes in both plasma and brain homogenate exhibited a good linearity within the concentration range(r>0.992 2). Their mean recoveries were between 58.86% and 112.1%. Intra-day and inter-day precisions of the investigated components exhibited RSD≤9.7%, and the accuracy(RE) ranged from -9.68% to 8.20% at all quality control levels. The results of accuracy and stability meet the requirements for biopharmaceutical analysis. For TSⅡA, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.58±0.081) h, (725.4±88.20) μg•L⁻¹, (2 101.3±124.85) μg•h•L⁻¹ and (3.66±0.05) h, respectively. For SAB, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.29±0.21) h, (307.9±46.75) μg•L⁻¹, (537.4±88.24) μg•h•L⁻¹ and (2.08±0.11) h, respectively. For GRg₁, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.42±0.20) h, (460.38±154.60) μg•L⁻¹, (383.4±88.16) μg•h•L⁻¹ and (1.87±0.046) h, respectively. For TSⅡA, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the brain tissue were (0.75±0.22) h, (1.41±0.42) ng•g⁻¹, (4.34±2.48) ng•h•g⁻¹ and (4.00±1.90) h, respectively. For SAB, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (1.08±0.20) h, (21.09±4.850) ng•g⁻¹, (14.83±3.160) ng•h•g⁻¹ and (0.99±0.08) h, respectively. For GRg₁, the pharmacokinetics parameters Tmax, Cmax, AUC0-t, MRTlast in the plasma were (0.50±0.16) h, (130.96±54.220) ng•g⁻¹, (136.24±34.350) ng•h•g⁻¹ and (2.87±0.33) h, respectively. The developed method was successfully applied in pharmacokinetic studies on content of TS ⅡA, SAB and GRg₁ in rat plasma and brain tissues.

Topics: Abietanes; Animals; Benzofurans; Brain; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Ginsenosides; Male; Plasma; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

To optimize the ethanol extraction process for Shenlian formula. On the basis of the pharmacodynamics index for different extraction process routes, the contents of salvianolic acid B, tanshinone ⅡA and berberine, as well as the extraction ratio in different experimental schemes were used as the ethanol extraction examining indexes, and multi-criterion synthesizing grading method was used for data analysis to optimize and verify the ethanol-extraction process conditions in orthogonal experiment. The optimum ethanol extraction process was as follows: adding 60% ethanol, 10 times amount, extracting for 2.0 h each time for a total of 2 times. This extraction process showed good stability and availability.

Topics: Abietanes; Benzofurans; Berberine; Drugs, Chinese Herbal; Ethanol; Plants, Medicinal; Technology, Pharmaceutical

In this study, we analyzed danshen (Salvia miltiorrhiza) constituents using biopartitioning and microemulsion high-performance liquid chromatography (MELC). The quantitative retention-activity relationships (QRARs) of the constituents were established to model their pharmacokinetic (PK) parameters and chromatographic retention data, and generate their biological effectiveness fingerprints. A high-performance liquid chromatography (HPLC) method was established to determine the abundance of the extracted danshen constituents, such as sodium danshensu, rosmarinic acid, salvianolic acid B, protocatechuic aldehyde, cryptotanshinone, and tanshinone IIA. And another HPLC protocol was established to determine the abundance of those constituents in rat plasma samples. An experimental model was built in Sprague Dawley (SD) rats, and calculated the corresponding PK parameterst with 3P97 software package. Thirty-five model drugs were selected to test the PK parameter prediction capacities of the various MELC systems and to optimize the chromatographic protocols. QRARs and generated PK fingerprints were established. The test included water/oil-soluble danshen constituents and the prediction capacity of the regression model was validated. The results showed that the model had good predictability.

Topics: Abietanes; Animals; Area Under Curve; Benzofurans; Chromatography, High Pressure Liquid; Cinnamates; Depsides; Drugs, Chinese Herbal; Emulsions; Male; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Rosmarinic Acid; Salvia miltiorrhiza; Surface-Active Agents

Based on the research of active liver targeting liposomes mediated by glycyrrhetinic acid ligand at home and abroad, this paper focuses on the liver targeting effect of liposomes mediated with 18-GA-Gly, a kind of glycyrrhetinic acid ligand. salvianolic acid B(Sal B)-tanshinone ⅡA (TSN)liposomes mediated by 18-GA-Gly as well as the liposomes with unmodified ligands were prepared by film dispersion-high pressure homogenization method, and then the particle size, potential, encapsulation efficiency and ligand binding rate were detected. Plasma samples of the heart, liver, spleen, lung and kidney tissues were taken at different time points after tail vein injections. The contents of Sal B and TSN in each sample were determined with UPLC methods and the liver targeting effect of 18-GA-Gly ligands was evaluated. The results showed that the particle size, potential, encapsulation efficiency and ligand binding rate met the basic requirements; in vivo targeting investigation results showed no difference between GLY-TS-Lip group and TS-Lip group. The liposomes mediated by glycyrrhetinic acid derivative ligand 18-GA-Gly can increase the peak concentration of Sal B and TSN in liver, but showed no significant liver targeting effect.

Topics: Abietanes; Animals; Benzofurans; Drug Carriers; Glycyrrhetinic Acid; Ligands; Liposomes; Liver

The root yield and active constituent contents were analyzed from four Salvia miltiorrhiza cultivars grown at three different locations( Zhuyang, Changqing, and Taian, Shandong Province) to determine the influence of environmental conditions and cultivars. .. Phenolic acids and tanshinones were analyzed by HPLC method. Total phenolic acids content were analyzed by FolinCiocalteu method. Klason method was used to determine the content of lignin.. The root yield and the active constituent contents were significantly affected by different environments and cultivars of Salvia miltiorrhiza. The root yield was negatively correlated with active constituent contents. Salvia miltiorrhiza of Zhuyang location had the highest active constituent content, but it had the lowest root yield. Salvia miltiorrhiza of Taian location had the lowest active constituent contents, while it had the highest root yield. Salvia miltiorrhiza of Changqing location had relatively higher bio-yields of phenolic acids and tanshinones, which made it suitable for Salvia miltiorrhiza cultivation. Furthermore, compared with three other cultivars,105 cultivar could remain the salvianolic acid B stable, which indicating that 105 cultivar was possible related to resistances.. The research provides a theoretical basis for the selecting of the optimal cultivar and the optimal environmental condition.

Topics: Abietanes; Benzofurans; Chromatography, High Pressure Liquid; Genotype; Hydroxybenzoates; Plant Roots; Salvia miltiorrhiza

The aim of this study was to investigate the pharmacokinetic interaction between tanshinones and polyphenolics which act as the main bioactive compounds in Saliva miltiorrhiza Bunge (SMB). Thus, a rapid and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine the concentrations of Tanshinone IIA (TSIIA), Tanshinone I (TI), Cryptotanshinone (CT), Salvianolic acid B (Sal B), Protocatechuic aldehyde (PAL), Rosmarinic acid (RA), and Danshensu (DSS) in rat plasma. The Sprague-Dawley rats were allocated to three groups which orally administered tanshinones (DST), polyphenolics (DFS), and a mixture of tanshinones and polyphenolics (DTF). These samples were processed by a simple liquid-liquid extraction (LLE) method with ethyl acetate. Chromatographic separation was achieved on an Acquity BEH C18 column (100 mm × 2. 1 mm, 1.7 µm) with the mobile phase consisting of 0.1% (v/v) formic acid and acetonitrile by gradient elution at a flow rate of 0.4 mL/min. The detection was performed on a triple quadrupole-tandem mass spectrometer TQ-MS/MS equipped with negative and positive electrospray ionization (ESI) interface in multiple reaction monitoring (MRM) mode. The statistical analysis was performed by the Student's t-test with P ≤ 0.05 as the level of significance. The method showed good precision, accuracy, recovery, sensitivity, linearity, and stability. The pharmacokinetic profiles and parameters of these polyphenolics changed when co-administrated with tanshinones. The tanshinones improved the bioavailability of DSS, accelerated the eliminating rate of RA and Sal B and promoted their distribution in vivo. They also contributed to promoting the biotransformation of Sal B to DSS. The polyphenolics could affect the pharmacokinetic of tanshinones, especially CT and TSIIA. Furthermore, the biotransformation of CT to TSIIA and the bioavailability of TSIIA were both improved. This study may provide useful information to avoid unexpected increase of the plasma drug concentration in the clinical practice. Copyright © 2015 John Wiley & Sons, Ltd.

Topics: Abietanes; Animals; Benzaldehydes; Benzofurans; Catechols; Chromatography, High Pressure Liquid; Cinnamates; Depsides; Lactates; Limit of Detection; Liquid-Liquid Extraction; Male; Phenanthrenes; Polyphenols; Rats, Sprague-Dawley; Rosmarinic Acid; Tandem Mass Spectrometry

Losartan (LST) is a common chemical drug used to treat high blood pressure and reduce the risk of stroke in certain people with heart disease. Danshen, prepared from the dried root and rhizome of Salvia miltiorrhiza Bunge, has been widely used for prevention and treatment of various cardiovascular and cerebrovascular diseases. There are more than 35 formulations containing Danshen indexed in the 2010 Chinese Pharmacopoeia, which are often combined with LST to treat cardiovascular and cerebrovascular diseases in the clinic. The effects of the two major components of Danshen, salvianolic acid B (SA-B) and tanshinone IIA (Tan IIA), on the pharmacokinetics of losartan and its metabolite, EXP3174, in rats were investigated by liquid chromatography coupled with mass spectrometry (LC-MS). Male Sprague-Dawley rats were randomly assigned to 3 groups: LST, LST+SA-B and LST+Tan IIA, and the main pharmacokinetic parameters were estimated after oral administration of LST, LST+SA-B and LST+Tan IIA. It was found that there are significant differences in the pharmacokinetic parameters among the three groups: Cmax, t1/2, AUC, AUMC in the LST+SA-B group was smaller than those in group LST, while larger in group LST+Tan IIA. Further, the effects of SA-B and Tan IIA on the metabolism of losartan was also investigated using rat liver microsomes in vitro. The results indicated that SA-B can induce the metabolism of LST, while Tan IIA can inhibit the metabolism of LST in rat liver microsomes in vitro by regulating activities of CYP450 enzymes. In addition, the effect of SA-B and Tan IIA on CYP3A4 and CYP2C9 expression was studied in Chang liver cells by western-blotting and Real-time PCR. It was concluded that the two components of Danshen, SA-B and Tan IIA have different influences on the metabolism of LST: SA-B can obviously speed up the metabolism of LST by inducing CYP3A4/CYP2C9 activities and expression, however, Tan IIA can slow down the metabolism of LST by inhibiting CYP3A4/CYP2C9 activities.

Topics: Abietanes; Animals; Antihypertensive Agents; Benzofurans; Cell Line; Cell Survival; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP3A; Drug Interactions; Drugs, Chinese Herbal; Losartan; Male; Mass Spectrometry; Microsomes, Liver; Rats, Sprague-Dawley; RNA, Messenger

Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA (Tan-IIA), salvianolic acid A (Sal-A) and salvianolic acid B (Sal-B), the important active compounds of Salvia miltiorrhiza Bunge, on areca nut extract (ANE)-induced oral submucous fibrosis (OSF) in vitro. Through human procollagen gene promoter luciferase reporter plasmid assay, hydroxyproline assay, gelatin zymography assay, qRT-PCR, ELISA and Western blot assay, the influence of these three compounds on ANE-stimulated cell viability, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion and the activation of PI3K/AKT, ERK/JNK/p38 MAPK and TGF-β/Smads pathways were detected. The results showed that Tan-IIA, Sal-A and Sal-B could significantly inhibit the ANE-stimulated abnormal viability and collagen accumulation of mice oral mucosal fibroblasts (MOMFs), inhibit the transcription of procollagen gene COL1A1 and COL3A1, increase MMP-2/-9 activity, decrease TIMP-1/-2 expression and inhibit the transcription and release of CTGF, TGF-β1, IL-6 and TNF-α; Tan-IIA, Sal-A and Sal-B also inhibited the ANE-induced activation of AKT and ERK MAPK pathways in MOMFs and the activation of TGF-β/Smads pathway in HaCaT cells. In conclusion, Tan-IIA, Sal-A and Sal-B possess excellent antifibrotic activity in vitro and can possibly be used to promote the rehabilitation of OSF patients.

Topics: Abietanes; Animals; Areca; Benzofurans; Caffeic Acids; Cell Line; Cell Survival; Collagen; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Fibroblasts; Gene Expression Regulation; Humans; In Vitro Techniques; Lactates; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Nuts; Oral Submucous Fibrosis; Plant Exudates; Proto-Oncogene Proteins c-akt; Signal Transduction; Smad Proteins; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Transforming Growth Factor beta

To elucidate the interaction between hydrophilic lithospermic acid B and lipophilic tanshinone II A in rats.. A reliable high-performance liquid chromatography method was adopted for simultaneous determination of lithospermic acid B and tanshinone II A in rat plasma, through which the pharmacokinetic interaction between lithospermic acid B and tanshinone II A by intravenous injection was investigated.. The simultaneous intravenous injection of tanshinone II A and lithospermic acid B significantly altered the pharmacokinetic parameters of both compounds when compared with the individual intravenous administration of each compound. The area under the concentration-time curve of tanshinone II A and lithospermic acid B increased by 18.35 and 59.31%, respectively. The mean retention time of tanshinone II A and lithospermic acid B increased, respectively, from 9.3 to 32.8 h and 20.2 to 49.1 h. The concomitant use of tanshinone II A magnified the volume of distribution at steady state (Vss) and time for the drug in the plasma to reduce the highest concentration by half (t½) of lithospermic acid B, while at the same time the Vss and t½ of tanshinone II A changed significantly in the presence of lithospermic acid B.. Lithospermic acid B and tanshinone II A interact with each other following simultaneous intravenous injection in rats and this observation may expand the clinical use of Danshen (Radix Salviae Miltiorrhizae).

Topics: Abietanes; Animals; Benzofurans; Chromatography, High Pressure Liquid; Depsides; Drug Interactions; Drugs, Chinese Herbal; Male; Rats; Rats, Wistar

To optimize the method in the Chinese Pharmacopoeia for determining Salviae Miltiorrhizae Radix et Rhizoma.. Tanshinone II(A) and salvianolic acid B were selected as the index in optimization of the sample preparation method of Salviae Miltiorrhizae Radix et Rhizoma in Chinese Pharmacopoeia. Orthogonal test was used to optimize the extraction process of Salviae Miltiorrhizae Radix et Rhizoma, and concentration of contents were detected by high performance liquid chromatography method. A detection of using methanol-water (85: 15) at wavelength of 270 nm was employed for tanshinone II(A) and a detection of using methanol-acetonitrile-formic acid-water (30:10:1: 59) at wavelength of 286 nm was employed for salvianolic acid B.. The optimized extraction process of tanshinone II(A) and salvianolic acid B was: extracted by 90% methanol and reflux twice (0.5 h each time) at 75 degrees C, extracted by 70% methanol and reflux twice (1.5 h each time) at 75 degrees C, respectively.. Optimized extraction and determination methods could be used to reflect the content of tanshinone II(A) and salvianolic acid B in Salviae Miltiorrhizae Radix et Rhizoma more accurately and efficiently.

Topics: Abietanes; Benzofurans; Chromatography, High Pressure Liquid; Rhizome; Salvia miltiorrhiza; Temperature

The change of yield and contents. of active compositions were studied while the fibrous roots were decayed naturally. HPLC method was used to detect the contents of active composition. The results show that fibrousroots could decrease the production of plant by 38.60% (20 g) and 30.99% (40 g), respectively. Treatment 1 could increase the contents of dihydrotanshinone and cryptotanshinone of Salvia miltiorrhiza f. alba by 26.08% and 22.64%, respectively. Compared with the comparison, treatment 2 decreased the contents of ihydrotanshinone, cryptotanshinone, tanshinone I and tanshinone II(A) of S. miltiorrhiza f. alba by 60.87%, 79.24%, 84.61% and 88.99%, respectively. Meanwhile, the total contents of the liposoluble constituents reduced by 86.27%. The different concentration of fibrousroots could increase the content of salvianolic acid B by 4.98% (20 g) and 23.64% (40 g), respectively. Meanwhile, the content of rosemary acid was increased by 4.98% (20 g) and 23.64% (40 g), respectively. The content of water-soluble constituents positively correlated to the mount of added fibrousroots, and the change was significantly. The result indicted that the decay of fibrousroots has a significant impact on the growth and the content of the active composition of S. miltiorrhiza f. alba under the condition of continuous cropping. Fibrousroots could decrease the content of biomass and liposoluble constituents significantly, which maybe one of the main factors to S. miltiorrhiza f. alba continuous cropping obstacle formation.

Topics: Abietanes; Benzofurans; Biomass; Chromatography, High Pressure Liquid; Plant Roots; Salvia miltiorrhiza

A simple and reliable method for distinguishing Danshen is important to evaluate the quality and clinical efficiency of these species. An HPLC method was developed for the determination of protocatechuic aldehyde, salvianolic acid A, salvianolic acid B, cryptotanshinone, tanshinone I and tanshinone IIA in 23 samples of Salvia. The analytes were separated on an Agilent XDB C18 reversed-phase column coupled with a Phenomenex C18 guard column using a gradient elution of acetonitile-0.1% aqueous phosphoric acid as the mobile phase at a flow rate 0.8 mL/min and UV detection at 280 nm. The method allowing the simultaneous quantification of six major active compositions was optimized and validated for linearity, precision, accuracy and limits of detection (LOD) and quantification. The LOD ranged from 0.019 to 0.850 µg/mL (R(2) ≥ 0.9998). Accuracy, precision and reproducibility were all within the required limits. The average recovery between 96.49 and 102.16% and the relative standard deviations were <3.01%. Based on the six compositions content and clustering result, this research results suggest that these six major active compositions could be distinguishing markers for Danshen and non-Danshen.

Topics: Abietanes; Benzofurans; Caffeic Acids; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Lactates; Limit of Detection; Phenanthrenes; Reproducibility of Results; Salvia; Salvia miltiorrhiza

The aim of this study was to systematically optimize and characterize the co-encapsulation process of Salvianolic acid B (Sal B), Tanshinone II A (TSN) and Glycyrrhetinic acid (GA) into liposomes. The liposomes (GTS-lip) were prepared using film hydration method combined with probe sonication to encapsulate two hydrophobic components (TSN and GA), and using pH gradient method to load hydrophilic component Sal B. The concentration of encapsulated drugs was measured by a reversed phase high performance liquid chromatography (RP-HPLC) method. Systematic optimization of encapsulation process was performed using single factor test, orthogonal test in combination with Box-Behnken Design. Optimum conditions are as follows: ratio of GA to lipid (w/w)=0.08, ratio of Sal B to lipid (w/w)=0.12 and pH of buffer=3.3. Based on the conditions mentioned above, encapsulation efficiency of Sal B, TSN and GA reached target levels: (96.03 ± 0.28)%, (80.63 ± 0.91)% and (88.56 ± 0.17)%, respectively. The GTS-lip had a unimodal size-distribution and a mean diameter of 191.3 ± 6.31 nm. Morphology determination of the GTS-lip indicated that the liposomes were spherical, and there was no free drug crystal in the visual field of transmission electron microscopy. Also, the ζ potential of GTS-lip was detected to be -11.6 ± 0.35 mV. In vitro release investigation of GTS-lip suggested that the release rate of GTS-lip significantly decreased compared to drug solution. The accumulative release percentage of TSN, GA and Sal B were 10% in 36 h, 4% in 36 h and 77% in 24 h. Meanwhile, GTS-lip exhibited definite activity on proliferative inhibition of hepatic stellate cells (HSC). GTS-lip decreased the viability of the HSC to higher than 75% at two high drug concentration groups in 24h. At the same time, GTS-lip of two low drug concentration groups increased the inhibition rates by 2.3 folds and 1.9 folds separately at 48 h compared to 24h. By contrast, inhibition activity of G-T-S solution group showed less change between 48 h and 24 h. The prolonged and enhanced activity in 48 h which GTS-lip group manifested might contribute to its sustained release effect.

Topics: Abietanes; Benzofurans; Cell Line; Cell Proliferation; Cell Survival; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Delayed-Action Preparations; Glycyrrhetinic Acid; Hepatic Stellate Cells; Humans; Hydrophobic and Hydrophilic Interactions; Liposomes; Microscopy, Electron, Transmission; Particle Size; Time Factors

Chlorogenic acid (1), salvianolic acid B (2), and tanshinone IIA (3) are commonly used as chemoprotective agents for chemotherapy in cancer patients. The present study deals with the effect of these three compounds on cytotoxicity of doxorubicin in HepG2 cells. The results showed that 1 and 2 reduced the cytotoxicity of doxorubicin through scavenging ROS generated by doxorubicin in HepG2 cells. The findings suggest that 1 and 2 could enhance the expression of SOD and decrease that of NADPH oxidase, which resulted in the elimination of ROS. On the contrary, 3 enhanced the cytotoxicity of doxorubicin in HepG2 cells. Furthermore, drug interactions between doxorubicin and 3 produce synergistic effects in HepG2 cells.

Topics: Abietanes; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Benzofurans; Caspase 3; Chlorogenic Acid; Doxorubicin; Hep G2 Cells; Humans; L-Lactate Dehydrogenase; NADPH Oxidase 4; NADPH Oxidases; Reactive Oxygen Species

The present study aimed to investigate the effect of Glomus versiforme and Trichodema harzianum on the growth and quality of Salvia miltiorrhiza continuous cropping under field conditions. The field plot experiment was conducted, these active components in the plant were analyzed by HPLC, the root diseases incidence rate of S. miltiorrhiza determined by observation and counting, and relative parameters were measured. The data was statistically processed. The result showed that inoculation of G. versiforme and combined inoculation of G. versiforme with T. harzianum significantly decreased the root diseases incidence rate of S. miltiorrhiza, and combined inoculation of G. versiforme with T. harzianum was better than other treatments. All treatments improved accumulation of active ingredients in root. Inoculation of G. versiforme and combined inoculation of G. versiforme with T. harzianum significantly increased the content of salvianolic acid B and cryptotanshinone of root (P < 0.05), Inoculation of G. versiforme, T. harzianum and combined inoculation of G. versiforme with T. harzianum significantly enhanced the content of tanshinone I and tanshinone II(A) of the root (P < 0.05). It may conclude that inoculation of G. versiforme and combined inoculation of G. versiforme with T. harzianum can effectively reduce the root diseases incidence of continuous cropping S. miltiorrhiza, and improve the quality of S. miltiorrhiza.

Topics: Abietanes; Antibiosis; Benzofurans; Glomeromycota; Host-Pathogen Interactions; Phenanthrenes; Plant Diseases; Plant Roots; Salvia miltiorrhiza; Trichoderma

To develop a LC-MS/MS method for the determination of protocatechuic acid, protocatechuic aldehyde, salvianolic acid A, salvianolic acid B, cryptotanshinone and tanshinone II(A) in rat plasma and brain. The plasma and brain samples were precipitated with ethyl acetate, then were separated on an Agilent eclipse plus-C18 column (2.1 mm x 50 mm, 3.5 microm) using acetonitrile (consisting of 0.1% formic acid) and water (consisting of 0.1% formic acid) as mobile phase in gradient elution mode. The mass spectrometer was operated under both positive and negative ion mode with the ESI source, and the detection was performed by MRM. The transition of 154.3/153.1 m/z for protocatechuic acid, 137.3/108 m/z for protocatechuic aldehyde, 493.0/295.2 m/z for Salvianolic acid A, 718.0/520.0 m/z for salvianolic acid B, 321.4/152.3 m/z for chloramphenicol, 297.4/254.3 m/z for cryptotanshinone, 295.5/249.3 m/z for tanshinone II(A) and 285.2/154.0 m/z for Diazepam. The calibration curves in the range of 0.625-1 000 microg x L(-1) for protocatechuic acid and protocatechuic aldehyde, 1.25-1 000 microg x L(-1) for salvianolic acid A, 2.5-1 000 microg x L(-1) for salvianolic acid B, 0.15-1 000 microg x L(-1) for cryptotanshinone, 0.625-1 000 microg x L(-1) for tanshinone II(A) are with good linearityin rat plasma and brain. The analysis method is sensitive, simple, and suitable enough to be applied in the pharmacokinetic study of the 6 main components. Animal testing gives the lgBB of the drugs and further studies of the 6 components cross the blood-brain barrier can be carried out.

Topics: Abietanes; Animals; Benzaldehydes; Benzofurans; Blood-Brain Barrier; Brain; Caffeic Acids; Catechols; Chromatography, Liquid; Hydroxybenzoates; Injections, Intravenous; Lactates; Phenanthrenes; Plant Preparations; Rats; Reproducibility of Results; Salvia miltiorrhiza; Tandem Mass Spectrometry

Salvia miltiorrhiza is a significant source of bioactive compounds providing human health effects. Here, we surveyed root yield and the active constituents' divergences of second generation S. miltiorrhiza (SP2) responding to a spaceflight environment. High-performance liquid chromatography was conducted for the comprehensive constituents' characterizations of 28 SP2 lines (224 individuals) and the ground control (eight individuals). The results showed that the mean fresh and dry weight of roots ranged from 116 to 172 g and 25 to 119 g, respectively, in SP2 lines. In addition, the mean contents of four tanshinone compounds (tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone I) of 28 SP2 lines varied from 0.32 to 1.04 mg · g(-1), 0.47 to 2.39 mg · g(-1), 0.25 to 1.60 mg · g(-1), and 0.53 to 1.67 mg · g(-1), respectively. Except for salvianolic acid B, which varied drastically from 72 % to 201 % of the ground control treatment, the other six phenolic acid contents of the 28 SP2 lines all increased after spaceflight. Principal component analysis was performed to obtain an overview of the distribution of all samples, and score plots clearly separated the SP2 accessions from ground controls. Moreover, a positive relationship was observed between tanshinone I and tanshinone IIA (r = 0.790, p < 0.01), and rosmarinic acid was positively correlated with salvianolic acid B (r = 0.728, p < 0.01). In conclusion, this study demonstrated that a spaceflight environment induced SP2 accessions remarkably in the variation of root yield and active constituent content.

Topics: Abietanes; Benzofurans; Biomass; Chromatography, High Pressure Liquid; Cinnamates; Depsides; Environment; Humans; Phenanthrenes; Plant Extracts; Plant Roots; Principal Component Analysis; Rosmarinic Acid; Salvia miltiorrhiza; Space Flight

Salvia miltiorrhiza Bunge (Labiatae sp. plant, Chinese name Danshen) and Panax notoginseng (Burk.) F. H. Chen (Araliaceae plant, Chinese name Sanqi) have a long history in treating coronary heart disease, cerebrovascular disease and inner ear disorders in traditional Chinese medicine. To provide a rational basis for the use of these herbs in clinical practice, we investigated the in vivo distribution and pharmacokinetics of marker agents in Danshen and Sanqi via intravenous and inner ear administration and explored the potential interactions of these agents in compound prescription.. Guinea pigs were given Danshen extracts (salvianolic acid B, tanshinone IIA), Sanqi extracts (Panax notoginseng saponins) and combination of the two extracts via intravenous and intratympanic administration (IT). Samples from the brain, inner ear perilymph (PL), cerebrospinal fluid (CSF) and plasma were collected at different time points. The concentration of salvianolic acid B (Sal B), tanshinone IIA (Ts IIA), notoginsenoside R₁ (R₁), ginsenoside Rg₁ (Rg₁) and ginsenoside Rb₁ (Rb₁) was determined by high-performance liquid chromatography coupled with a diode array detector (DAD). Pharmacokinetic parameters were estimated using non-compartmental methods.. Local drug application via inner ear greatly improved drug distribution within the PL, CSF and brain tissues compared with intravenous administration (IV). The values of Cmax and AUC(0-t) after IT were significantly higher than IV. In comparison with IT of Danshen and Sanqi alone, the pharmacokinetic parameters for R₁, Rg₁, Rb₁, Sal B and Ts IIA were markedly different in the compound prescription. The compound compatibility enhanced the transport of Danshen components into the brain through the inner ear and apparently prolonged the retention time in CSF while decreasing the distribution of Sanqi components in the inner ear and brain.. The results indicated that local drug application to the inner ear was a more effective delivery route than systemic administration. Co-administration of Danshen and Sanqi could cause significant pharmacokinetic herb-herb interactions in guinea pigs. The multiple active components via inner ear administration might be promising candidates for the treatment of inner ear and brain diseases.

Topics: Abietanes; Animals; Benzofurans; Cerebrospinal Fluid; Drugs, Chinese Herbal; Ear, Inner; Ginsenosides; Guinea Pigs; Herb-Drug Interactions; Medicine, Chinese Traditional; Panax notoginseng; Salvia miltiorrhiza

Inflammation plays a crucial role in the pathophysiology of atherosclerosis. Besides cytokines, chemokines and cell adhesion molecules, CD40 and P-selectin play important roles as key regulators of the inflammatory process in atherosclerosis. Danshen (DS) is commonly used in traditional Chinese medicine for therapy of cardiovascular diseases such as coronary artery disease. The aim of the present study was to evaluate the protective effects of DS with respect to possible anti-inflammatory effects. Human umbilical vein endothelial cells as well as platelets were incubated with an extract of DS or one of its major ingredients salvianolic acid B (Sal B), tanshinone IIA (Tansh) and protocatechuic acid (Protoc) under tumor necrosis factor (TNF)-α or ADP stimulation. Expression of CD40 and cellular adhesion molecules (VCAM-1/ICAM-1) were assessed via flow cytometry. Levels of interleukin (IL)-6, IL-8, monocyte-chemoattractant-protein (MCP)-1 as well as soluble VCAM1 and ICAM-1 in the supernatants were examined via luminex based analysis. Treatment with DS attenuated TNF-α induced expression of CD40. Furthermore, the expression of VCAM-1 and ICAM-1 as well as the release of soluble VCAM-1 and ICAM-1 were downregulated. In the cell supernatants we also observed a significant reduction of IL-6, IL8 and MCP-1. DS and its major ingredients, Sal B and Protoc, significantly inhibited TNF-induced expression and release of adhesion molecules, cytokines and chemokines as well as ADP-induced expression of platelet P-selectin. Because of the key roles of inflammatory mediators in the etiology of atherosclerosis, this work provides useful insight in understanding the pharmacological efficacy of Chinese herbal medicine.

Topics: Abietanes; Adenosine Diphosphate; Anti-Inflammatory Agents; Atherosclerosis; Benzofurans; Blood Platelets; CD40 Antigens; Cells, Cultured; Chemokine CCL2; Down-Regulation; Drugs, Chinese Herbal; Human Umbilical Vein Endothelial Cells; Humans; Hydroxybenzoates; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; P-Selectin; Salvia miltiorrhiza; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Biotic elicitors can be used to stimulate the production of secondary metabolites in plants. However, limited information is available on the effects of biotic elicitors from endophytic fungi on their host plant. Trichoderma atroviride D16 is an endophytic fungus isolated from the root of Salvia miltiorrhiza and previously reported to produce tanshinone I (T-I) and tanshinone IIA (T-IIA). Here, the effects of extract of mycelium (EM) and the polysaccharide fraction (PSF), produced by T. atroviride D16, on the growth and secondary metabolism of S. miltiorrhiza hairy roots are reported. The results indicated that both EM and PSF promoted hairy root growth and stimulated the biosynthesis of tanshinones in hairy roots. EM slightly suppressed the accumulation of phenolic acids, while PSF had no significant influence on the accumulation of these compounds. When comparing the effects of EM versus PSF, it was concluded that PSF is one of the main active constituents responsible for promoting hairy root growth, as well as stimulating biosynthesis of tanshinones in the hairy root cultures. Moreover, the transcriptional activity of genes involved in the tanshinone biosynthetic pathway increased significantly with PSF treatment. Thus, PSF from endophytic T. atroviride D16 affected the chemical composition of the host plant by influencing the expression of genes related to the secondary metabolite biosynthetic pathway. Furthermore, treatment with PSF can be effectively utilized for large-scale production of tanshinones in the S. miltiorrhiza hairy root culture system.

Topics: Abietanes; Benzofurans; Biomass; Cinnamates; Depsides; Endophytes; Gene Expression Regulation, Plant; Mycelium; Phenols; Plant Roots; Polysaccharides; Rosmarinic Acid; Salvia miltiorrhiza; Trichoderma

The aim of this study was to develop novel multiple agents loaded poly (D,L-lactide-co-glycolide acid) (PLGA) nanoparticles (NPs) and evaluate their potential for brain delivery via inner ear administration. PLGA NPs loaded with salvianolic acid B (Sal B), tanshinone IIA (TS IIA) and panax notoginsenoside (PNS) were prepared by double emulsion/solvent evaporation method. It was observed that optimized NPs displayed satisfactory encapsulation efficiency and desired sustained-release characteristics. NPs following intratympanic administration (IT) in guinea pigs greatly improved drug distribution within the inner ear, cerebrospinal fluid (CSF) and brain tissues compared with intravenous administration (IV). Pharmacodynamic studies demonstrated that NPs following IT markedly inhibited oxidizing reactions and protected the brain from cerebral ischemia reperfusion (I/R) injury by upregulating superoxide dismutase (SOD) activity both in serum and brain tissues, simultaneously significantly reducing the levels of malondialdehyde (MDA) and nitric oxide synthase (NOS). Moreover intratympanic delivery did not cause injury of cochlear function by preliminary study on the toxicity. These findings suggested that PLGA NPs-based delivery system via inner ear administration was a promising candidate to brain delivery for the treatment of brain diseases.

Topics: Abietanes; Animals; Benzofurans; Brain; Carotid Arteries; Drug Administration Routes; Drug Carriers; Ear, Inner; Ginsenosides; Guinea Pigs; Lactic Acid; Male; Nanoparticles; Neuroprotective Agents; Panax notoginseng; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Reperfusion Injury

To establish a LC-MS/MS method for determining the concentration of tanshinone IIA, salvianolic acid B and paeoniflorin of refined coronary cataplasm in rabbit plasma, in order to determine the concentration of the three main ingredients in blood after transdermal administration and calculate their pharmacokinetic parameters.. Rabbits were given refined coronary cataplasm on the basis of 15 g x kg(-1) by transdermal administration to detect the plasma concentration of the three main ingredients using LC-MS/MS. Winnonlin software was used to calculate their major pharmacokinetic parameters.. Tanshinone IIA, salvianolic acid B and paeoniflorin showed good linearity (r>0.999) at 1-100, 50-1 000, 10-1 000 microg x L(-1) respectively in plasma, with average recovery rate of 96.57%, 91.90%, 95.93%, respectively. The RSD within day were less than 15%. After transdermal administration of refined coronary cataplasm in rabbits, the main pharmacokinetic parameters of tanshinone IIA, salvianolic acid B or paeoniflorin were as follows: Cmax (20.85 +/- 12.68), (636.25 +/- 386.91), (787.80 +/- 395.64) microg x L(-1); Tmax (0.49 +/- 0.28), (0.44 +/- 0.27), (0.46 +/- 0.30) h.. The LC-MS/MS method is highly selective and sensitive to determine the concentration of samples in rabbit plasma. The pharmacokinetic characteristics of tanshinone IIA, salvianolic acid B and paeoniflorin are suitable to assess the percutaneous absorption of refined coronary cataplasm.

Topics: Abietanes; Animals; Benzoates; Benzofurans; Bridged-Ring Compounds; Chromatography, Liquid; Coronary Disease; Drugs, Chinese Herbal; Glucosides; Humans; Male; Monoterpenes; Rabbits; Tandem Mass Spectrometry

This study investigated the effects of Danshen and its active ingredients on the protein expression and enzymatic activity of CYP1A2 in primary rat hepatocytes. The ethanolic extract of Danshen roots (containing mainly tanshinones) inhibited CYP1A2-catalyzed phenacetin O-deethylation (IC(50)=24.6 μg/ml) in primary rat hepatocytes while the water extract containing mainly salvianolic acid B and danshenshu had no effect. Individual tanshinones such as cryptotanshinone, dihydrotanshinone, tanshinone IIA inhibited the CYP1A2-mediated metabolism with IC(50) values at 12.9, 17.4 and 31.9 μM, respectively. After 4-day treatment of the rat hepatocytes, the ethanolic extract of Danshen and tanshinone I increased rat CYP1A2 activity by 6.8- and 5.2-fold, respectively, with a concomitant up-regulation of CYP1A2 protein level by 13.5- and 6.5-fold, respectively. CYP1A2 induction correlated with the up-regulation of mRNA level of aryl hydrocarbon receptor (AhR), which suggested a positive feedback mechanism of tanshinone I-mediated CYP1A2 induction. A formulated Danshen pill (containing mainly danshensu and salvianolic acid B and the tanshinones) up-regulated CYP1A2 protein expression and enzyme activity, but danshensu and salvianolic acid B, when used individually, did not affect CYP1A2 activity. This study was the first report on the Janus action of the tanshinones on rat CYP1A2 activity.

Topics: Abietanes; Animals; Benzofurans; Cell Survival; Cytochrome P-450 CYP1A2; Cytochromes; Drugs, Chinese Herbal; Enzyme Activation; Enzyme Induction; Ethanol; Hepatocytes; Male; Phenacetin; Phenanthrenes; Phenanthrolines; Primary Cell Culture; Rats; Rats, Sprague-Dawley; Receptors, Aryl Hydrocarbon; RNA, Messenger; Salvia miltiorrhiza; Tacrine

Drying is the most common and fundamental procedure in the post-harvest processing which contributes to the quality and valuation of medicinal plants. However, attention to and research work on this aspect is relatively poor. In this paper, we reveal dynamic variations of concentrations of five major bioactive components, namely salvianolic acid B (SaB), dihydrotanshinone I, cryptotanshinone, tanshinone I and tanshinone IIA, in roots of Salvia miltiorrhiza (Dashen) during the drying process at different oven temperatures. A minor amount of SaB was found in fresh materials while an noticeable increase in SaB was detected in drying at 50~160 °C. The maximal value occurred after 40 min of drying at 130 °C and its variation showed a reverse V-shaped curve. Production of SaB exhibited a significant positive correlation with drying temperatures and a significant negative correlation with sample moistures. The amounts of tanshinones were nearly doubled in the early stage of drying and their variations showed similar changing trends with drying temperatures and sample moistures. The results supported our speculation that postharvest fresh plant materials, especially roots, were still physiologically active organs and would exhibit a series of anti-dehydration mechanisms including production of related secondary metabolites at the early stage of dehydration. Hence, the proper design of drying processes could contribute to promoting rather than reducing the quality of Danshen and other similar medicinal plants.

Topics: Abietanes; Benzofurans; Chromatography, High Pressure Liquid; Desiccation; Drugs, Chinese Herbal; Medicine, Chinese Traditional; Phenanthrenes; Plant Roots; Salvia miltiorrhiza

This study provides a desirable candidate gene resource (SmAOC) to increase the content of valuable natural products via appropriate JA pathway genetic engineering. Jasmonates (JAs) are important signal molecules in plants. They regulate transcripts of defense and secondary biosynthetic metabolite genes in response to environmental stresses. Currently, JAs are widely used as elicitors to improve the content of useful secondary metabolism in plants. Synthesis of the naturally occurring enantiomer of various jasmonates is catalyzed by allene oxide cyclase (AOC, EC 5.3.99.6). Here, we cloned and characterized the AOC gene (SmAOC) from Salvia miltiorrhiza. As expected, SmAOC expression was induced by abiotic stimuli such as methyl jasmonate (MeJA), ultraviolet radiation (UV) and low temperature (4 °C) in S. miltiorrhiza plantlets. To demonstrate whether the engineered internal JAs pool by overexpressing AOC gene could promote secondary metabolism production, the SmAOC was incorporated into S. miltiorrhiza hairy roots. The results revealed that SmAOC overexpression significant enhanced the yields of tanshinone IIA, rosmarinic acid (RA) and lithospermic acid B (LAB) in S. miltiorrhiza hairy roots. In addition, expression levels for key genes involved in the biosynthetic pathway of diterpenes and phenolic acids were also altered. These suggest that genetic manipulation of AOC would be helpful for improving the production of valuable secondary metabolites by regulating the biosynthesis of JAs.

Topics: Abietanes; Acetates; Benzofurans; Cinnamates; Cloning, Molecular; Cold Temperature; Cyclopentanes; Depsides; Diterpenes; Escherichia coli; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Plant; Genes, Plant; Genetic Engineering; Genetic Vectors; Hydroxybenzoates; Intramolecular Oxidoreductases; Oxylipins; Plant Roots; Rosmarinic Acid; Salvia miltiorrhiza; Transgenes; Ultraviolet Rays

Tanshinone IIA (T), salvianolic acid B (S) and ginsenoside Rb1 (G) are the three major active ingredients of Compound Danshen Formula (CDF) for its protective effects on myocardial ischemia (MI). In this study, we aimed to investigate therapeutic and synergistic effects of TSG (combination of T, S and G) on MI rats with metabolomic strategy.. MI model were induced in Sprague-Dawley rats by left anterior descending coronary artery ligation. MI rats were respectively administrated T, S, G, TSG and CDF. Plasma was analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Partial least squares discriminate analysis (PLS-DA) models were built to evaluate the therapeutic and synergistic effects of TSG at whole level. 22 MI biomarkers in rat plasma were also investigated to explain that.. TSG brings nearly equal therapeutic effects on MI as CDF and it plays more stable regulated action on those 22 identified metabolites than single compound.. Overall, there were few methods for the study of synergistic effects of Chinese medicine. Our results suggested that metabolomics offers a new idea for Chinese medicine research.

Topics: Abietanes; Animals; Benzofurans; Chromatography, Liquid; Ginsenosides; Male; Mass Spectrometry; Metabolomics; Rats; Rats, Sprague-Dawley

Salvia miltiorrhiza (Danshen) has been widely used for the treatment of cardiac and cerebrovascular disease throughout history. The objective of this study is to further elucidate the mechanisms underlying Danshen's cardiac protective effects to support its clinical evidence.. AND RESULTS: Salvianolic acid B (Sal B) and Tanshinone IIA (Tan IIA) are two of the major components in Danshen. We observed that Sal B and Tan IIA have cardioprotective effects in an in vivo myocardial infarction model of C57 mice, have vasodilator action in a ex vivo micro-artery system through the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway and are involved in the regulation of the L-arginine/eNOS/NO pathways in human umbilical vein endothelial cells (HUVECs). Both Sal B and Tan IIA inhibited cardiac hypertrophy and infarction sizes and improved cardiac function at 4 weeks after induction of infarction. Furthermore, an eNOS inhibitor (L-NAME) obliterated the observed effects. Sal B and Tan IIA mediated vasodilatation in mice coronaries ex vivo, the effect of which was decreased with either L-NAME or PI3K inhibitor (LY294002). In addition, Sal B and Tan IIA-induced vasodilatation was observed ex vivo in the microvessels of eNOS-/- mice. Sal B and Tan IIA also stimulated eNOS phosphorylation in a concentration- and time-dependent manner in the HUVEC culture, which was diminished by LY294002. In addition, Sal B and Tan IIA were found to stimulate the phosphorylation of AMPK (Thr(172)) and Akt (Ser(473)), while compound C significantly decreased the phosphorylation of Akt (Ser(473)) mediated by both. Finally, Sal B and Tan IIA were found to increase NO production, induce [(3)H]-L-arginine uptake and increase the CAT-1 and CAT-2B mRNA levels in HUVEC culture.. These findings suggest that both Sal B and Tan IIA have cardioprotective function in certain levels through multiple targets related with NO production, such as eNOS phosphorylation, L-arginine uptake and CAT expression, which may have major clinical implications.

Topics: Abietanes; Amino Acid Transport Systems, Basic; AMP-Activated Protein Kinases; Analysis of Variance; Animals; Arginine; Benzofurans; Cardiovascular Agents; Cationic Amino Acid Transporter 1; Cells, Cultured; Chromones; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Endothelial Cells; Enzyme Inhibitors; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Morpholines; Myocardial Infarction; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase Type III; Phosphatidylinositol 3-Kinase; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; RNA, Messenger; Signal Transduction; Time Factors; Vasodilation

The plant density-dependent variations in the root yield and content, and the yield of biomarkers in Australian grown Salvia miltiorrhiza Bunge, a commonly used Chinese medicinal herb for the treatment of cardiovascular diseases, were investigated in a field trial involving six different plant densities. The key biomarker compounds cryptotanshinone, tanshinone I, tanshinone IIA, and salvianolic acid B were quantified by a validated RP-HPLC method, and the root yields were determined per plant pair or unit area. There were significant variations (p<0.05) in the root yields and contents and the yields of the biomarkers between the different plant densities. Positive linear correlations were observed between the contents of the three tanshinones, whereas negative linear correlations were revealed between the contents of the tanshinones and salvianolic acid B. The highest root yield per plant pair was achieved when the plants were grown at 45×30 cm or 45×40 cm, whereas the highest root production par unit area was obtained for a plant density of 30×30 cm. The highest contents of the three tanshinones and the most abundant production of these tanshinones per unit area were achieved when the plants were grown at 30×30 cm. However, the highest content of salvianolic acid B was found for a density of 45×40 cm, while its highest yield per unit area was obtained for densities of 30×40 cm or 45×30 cm. The findings suggest that the plant density distinctly affects the root yield and content and the yield of tanshinones and salvianolic acid B in Australian grown S. miltiorrhiza, which may be used as a guide for developing optimal agricultural procedures for cultivating this herb.

Topics: Abietanes; Australia; Benzofurans; Phenanthrenes; Plant Roots; Salvia miltiorrhiza

In order to provide a scientific water management for the standardized cultivation, the effects of soil water content on the seedlings growth and active ingredients of S. miltiorrhiza were studied.. A water stress experiment with pot culture was applied to study the effects of different soil water content on the seedlings growth, biomass and the accumulation of tanshinone, salvianolic acid B and mineral nutrition of S. miltiorrhiza.. Soil water content had serious influence on the growth, yield, outer appearance and inner quality of S. miltiorrhiza when the soil was under severe drought or with too much water. But the shoot and root biomass of S. miltiorrhiza was increased significantly under mild drought. As well as the content and cumulant of dihydrotanshinone I , cryptotanshinone, tanshinone I , tanshinone IIA and salvianolic acid B in root of mild drought were increased. It also enhanced the P, K, Ca, Mg, Mn, Zn, Cu and Fe contents of S. miltiorrhiza under mild drought.. The overall results from the experiment suggest that the appropriate soil water content is 55% to 60% in seedling stage of S. miltiorrhiza. And it will be strongly recommended that the ridge culture and suitable soil moisture management must be carry out in production of S. miltiorrhiza in order to improve the yield and quality of medicinal materials.

Topics: Abietanes; Benzofurans; Biomass; Minerals; Plant Roots; Salvia miltiorrhiza; Seedlings; Soil; Stress, Physiological; Water

Radix Salvia miltiorrhiza (RSM), a traditional Chinese medicinal herb, has been alleged to possess therapeutic effects against senile dementia, also known as Alzheimer's disease (AD). However, the effects of the major components in RSM on cytotoxicity induced by amyloid-β peptide (Aβ) and on acetylcholinesterase activity have not been studied in depth to date. In this report, the effects of RSM aqueous/ethanol extracts, total polyphenols, total tanshinones and 3 phenolic compounds against toxicity mediated by Aβ(25-35) were tested with PC-12 cells. The results showed that Aβ(25-35)-induced cytotoxicity was revised by RSM aqueous/ethanol extracts and total polyphenols and that danshensu and salvianolic acid B could protect PC-12 cells by blocking Aβ(25-35)-induced Ca(2+)-intake, lactate dehydrogenase release, cell viability decrease and apoptosis. In addition, the activities of RSM extracts and relevant constituents in their inhibition of acetylcholinesterase were investigated using rat brain homogenates as an enzyme resource. Galanthamine hydrobromide, an accepted acetylcholinesterase inhibitor, was employed as a positive control agent. Our preliminary studies demonstrated that RSM ethanol extract, total tanshinones, tanshinone I and dihydrotanshinone I had remarkable inhibition effects on acetylcholinesterase in vitro. These findings suggest that both tanshinones and polyphenols in RSM are the active constituents responsible for the beneficial effects of this herb in AD treatment.

Topics: Abietanes; Amyloid beta-Peptides; Animals; Antioxidants; Apoptosis; Benzofurans; Calcium; Cell Survival; Cholinesterase Inhibitors; Hydroxybenzoates; L-Lactate Dehydrogenase; Male; Neuroprotective Agents; PC12 Cells; Phosphatidylinositols; Plant Extracts; Polyphenols; Rats; Rats, Sprague-Dawley; Salvia miltiorrhiza; Tetrazolium Salts; Thiazoles

Study the yield and quality of Salvia miltforthiza in the poplars and apple trees intercropping system.. Assay the yield, heavy metals, organochlorine pesticides and active components of Salvia miltforthiza in different intercropping systems are different.. The contents of Cd exceeds the allowed figure seriously though other heavy metals such as Pb, As, Hg, Cu fell in the standard range. The contents of organochlorine pesticides of different Salvia miltforthiza fell in the standard range. The active components of biennial Salvia miltforthiza intercropping with apple trees, including Tanshinone II A and Salvianolic acid B complied with the quality standards of Pharmacopoeia.. Soil fertility, heavy metals of intercropping system and planting years should be considered in order to ensure the quality and stability of Chinese medicine.

Topics: Abietanes; Agriculture; Benzofurans; Biomass; China; Malus; Metals, Heavy; Pesticide Residues; Plants, Medicinal; Quality Control; Salvia; Soil; Trees

Danshen (Salvia miltiorrhiza Bunge, Lamiaceae) is a commonly used and highly valued Chinese medicinal herb grown widely in China. In the present work, we studied cultivar variations of Australian-grown Danshen in order to select optimal cultivars for local herbal production. Root yields of seven cultivars, V1-V7, were monitored in a one-year field trial, and bioactive markers, including cryptotanshinone, tanshinone I, tanshinone IIA, and salvianolic acid B, were quantitatively determined using a validated RP-HPLC method. Significant variations were found in root yields, root production efficiencies, and contents of the bioactive marker compounds. Linear correlations were observed among the contents of three tanshinones but not among those of tanshinones and salvianolic acid B. Among the cultivars, V6 was the best cultivar for production of tanshinones, and V4 and V5 were best for production of salvianolic acid B. The findings indicate that it is possible to achieve optimal root yields, and high contents of tanshinones and salvianolic acid B by selecting specific Danshen cultivars.

Topics: Abietanes; Australia; Benzofurans; Chromatography, High Pressure Liquid; Medicine, Chinese Traditional; Phenanthrenes; Plant Roots; Salvia miltiorrhiza

Seasonal variations in contents of bioactive markers in Australian-grown Salvia miltiorrhiza roots were investigated in a two-year field trial. Cryptotanshinone, tanshinone I, tanshinone IIA, and salvianolic acid B were quantitatively determined by reversed-phase (RP) HPLC. Similar accumulation patterns were observed for the three tanshinones throughout the trial period, although roots harvested in the first year was found to contain relatively higher contents of these compounds. In contrast, the content of salvianolic acid B was peaked at 250 days after planting in the first year, and subsequently maintained at a plateau level in the second-year period. Linear correlations between the contents of individual tanshinones were observed, but not between those of tanshinones and salvianolic acid B. The findings suggest that tanshinones and salvianolic acid B have different accumulation patterns in Australian-grown Salvia miltiorrhiza roots, which should be critically considered for optimum harvesting of the roots for pharmaceutical applications.

Topics: Abietanes; Australia; Benzofurans; Biomarkers; Chromatography, High Pressure Liquid; Phenanthrenes; Plant Roots; Salvia miltiorrhiza; Seasons

Salvia miltiorrhiza f. alba (Baihua Danshen) is a Chinese medicinal herb commonly used for treating cardiovascular disease. It has been grown in Australia, although the quality of its main medicinal part (dried root) has not been assessed. In this study, we investigated HPLC profiles and biomarker contents of Australian-grown S. miltiorrhiza f. alba roots. Patterns of HPLC profiles were established in MeOH, and aqueous extracts in terms of number of common characteristic peaks and their relative retention times. The contents of three tanshinone biomarkers (cryptotanshinone (3), tanshinone I (1), and tanshinone IIA (2)) were significantly higher (p<0.05) in the roots of one-year-old plants than those of two-year-old plants. In contrast, salvianolic acid B (4) content was significantly higher in the roots of two-year-old plants than in those of one-year-old plants. The findings suggest that the biomarker contents in Australian-grown S. miltiorrhiza f. alba roots vary with the growth periods of the plants, which may be important in determining the optimal harvest time for the plant roots with targeted levels of tanshinones and salvianolic acid B (4).

Topics: Abietanes; Australia; Benzofurans; Biomarkers; Chromatography, High Pressure Liquid; Phenanthrenes; Plant Roots; Plants, Medicinal; Salvia miltiorrhiza

To establish a new method using AOTF-Near infrared spectroscopy (NIRS) for quick determination of tanshinone II(A) and salvianolic acid B in Fufang Danshen tablets.. HPLC was used as a reference method to determine the contents of tanshinone II(A) and salvianolic acid B in Fu Fang Dan Shen tablets. Multivariate calibration models based on PLS1 algorithm were developed to correlate the spectra and the corresponding values determined by the reference methods.. RMSECV (root-mean-square error of cross-validation) of the models for tanshinone II(A) and salvianolic acid B were 0.0103 and 0.1868 respectively. The correlation coefficients of the calibration models were 0.9873 and 0.9832 respectively. External validation with external validation samples proved that the relative coefficient of the predicted value and the truth value were R2 = 0.9743 and R2 = 0.9886 respectively, with measured recycle rates of 103.0% and 99.0%.. NIRS can be used in the determination of tanshinone II(A) and salvianolic acid B, which sets up the foundation of product-line control of Fuang Danshen tablets.

Topics: Abietanes; Benzofurans; Drugs, Chinese Herbal; Phenanthrenes; Reproducibility of Results; Spectroscopy, Near-Infrared; Tablets

To investigate the feasibility of extracting the fat-soluble and the water-solubility substances from Salviae Miltiorrhizae with O/W Microemulsion.. With the yield of Tanshinone IIA and Salvianolic acid B as index, compere with efficiency of extracting Salviae Miltiorrhizae by suing the different media (water, alcohol and microemulsion), using different extraction methods (heat, microwave, ultrasonic), using different formulations of O/W microemulsion.. The extracting yield of Tanshinone IIA and Salvianolic acid B are more than 70% by using microemulsion at mean time. It is good of the abilities of extraction of liposolubility compounds such as the Tanshinone IIA by the microemulsion. The formulations of microemulsion have remarkable effect for extracting Salviae Miltiorrhizae.. It is feasibiale that extracted Salviae Miltiorrhizae by using O/W microemulsion as a solvents.

Topics: Abietanes; Benzofurans; Drugs, Chinese Herbal; Emulsions; Oils; Phenanthrenes; Reproducibility of Results; Salvia miltiorrhiza; Water

To investigate the growth inhibiting and apoptosis inducing mechanisms of different matches of Tanshinone IIA and Salvianolic Acid B on Acute Promyelocytic Leukemia Cells (HL-60).. The HL-60s' growth inhibition and apoptosis-induced rates were detected by MTT reduction assay and flow cytometry with various matches of TanIIA and SalB.. The HL-60s' growth inhibition and apoptosis-induced rates were found higher in the group of TanIIA plus SalB than other single groups, and in the group TanIIA-SalB (10-5 microg/ml) they were the highest (P<0.05).. TanIIA and SalB both have obviously growth inhibiting and apoptosis inducing effect, and union groups show stronger effect than any single group, while different matching proportion results in different growth inhibiting and apoptosis inducing action.

Topics: Abietanes; Antineoplastic Agents, Phytogenic; Apoptosis; Benzofurans; Cell Proliferation; Drugs, Chinese Herbal; Flow Cytometry; HL-60 Cells; Humans; Leukemia, Promyelocytic, Acute; Phenanthrenes; Plants, Medicinal; Salvia miltiorrhiza

Salvia Miltiorrhiza Bunge (SMB), a traditional Chinese medicinal herb, has been alleged to support bone healing. However, the effects of the isolated major components of SMB on osseous cells and their corresponding effective doses are still unclear. In the present study, the effects of three components of SMB, including tanshinone IIA (Ts), salvianolic acid B (salB) and protocatechuic aldehyde (Pca), on mesenchymal bone marrow cells with the potential for osteoblastic differentiation were investigated. Various concentrations of Ts, salB and Pca were added to a rat bone marrow cell culture. The total metabolic activity and differentiation of bone marrow cells were evaluated by a metabolic assay and alkaline phosphatase (ALP) activity, respectively. The morphology and number of cells was observed by phase contrast microscopy and fluorescent microscopy after propidium iodide staining, respectively. Ts suppressed the growth and differentiation of bone precursor cells. SalB exhibited a biphasic effect: the high concentration of 160 microg/mL significantly depressed the population of bone marrow cells, however, lower concentrations (3-80 microg/mL) enhanced the total metabolic activity and their ALP expression. Pca suppressed the bone marrow cell population in a dose-dependent manner. Therefore, SalB has the potential to ameliorate bone healing by stimulating both the total metabolic activity and ALP activity of osteoblastic cells. Aqueous extracts, which preferably contain salB over Pca and are free of Ts therefore are recommended for bone formation.

Topics: Abietanes; Alkaline Phosphatase; Animals; Benzaldehydes; Benzofurans; Bone Marrow Cells; Catechols; Cell Differentiation; Cells, Cultured; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Male; Mesenchymal Stem Cells; Osteoblasts; Osteogenesis; Phenanthrenes; Rats; Rats, Sprague-Dawley; Salvia miltiorrhiza

The pharmacokinetics of the main components of protocatechualdehyde, salvianolic acid B, tanshinone II(A), cryptotanshinone, and the hydrophilic or lipophilic extracts of Salvia Miltiorrhiza Bge., in rat plasma were studied after oral administration separately to explore the interactions between them. Some components in the hydrophilic extract depress the absorption of the protocatechualdehyde, on the contrary, enhance the absorption of the salvianolic acid B and depress its elimination rate. The concomitant components in the lipophilic extract might enhance the absorption of cryptotanshinone and its distribution from the centre compartment to the peripheral compartment, and the metabolism to tanshinone II(A). The 'concomitant components' in the extract of Chinese material medica had significant effect on the pharmacokinetics of its 'marker components'. It can not only be rival, synergic, but also have the effects on metabolism. Therefore the traditional Chinese medicine was a complicated system, It should be taken a scientific and dialectic view in the research and development processes.

Topics: Abietanes; Animals; Area Under Curve; Benzaldehydes; Benzofurans; Catechols; Drug Interactions; Female; Male; Metabolic Clearance Rate; Molecular Structure; Phenanthrenes; Plant Extracts; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Salvia miltiorrhiza

Danshen root (Salvia miltiorrhiza Radix et Rhizoma) is a representative Chinese herb containing multiple components contributing to its polyvalent bioactivities. Advanced analysis approaches are needed to obtain a comprehensive picture of the targeting constituents in complete matrix. In this study, a chromatographic fingerprinting method to monitor simultaneously the hydrophilic and lipophilic constituents was developed for the quality evaluation of Danshen root and its preparations. Ten hydrophilic and nine lipophilic components were identified using HPLC-diode array detection-electrospray-MS (HPLC-DAD-ESI/MS) by comparing with the available references and reported data. Using the established method, 13 Danshen root samples collected from different sources, and 21 batches of Danshen preparations including tablets, injections, capsules, and dropping pills produced by different manufacturers were analyzed and their chromatographic fingerprints (CFP) were constructed. The results showed that the products of Danshen roots such as the tablets and capsules contained both the hydrophilic and lipophilic components, while the injections and dropping pills contained mainly the hydrophilic components. Principal components analysis (PCA) was applied for the statistical analysis of the fingerprinting data of crude herb and its preparations. The established CFPs demonstrate the representative chemical profiling of the existing components and can be applied to the authentication and quality assessment of Danshen roots and other Danshen containing formulated preparations.

Topics: Abietanes; Benzofurans; Caffeic Acids; Chromatography, High Pressure Liquid; Cinnamates; Diterpenes; Drugs, Chinese Herbal; Lactates; Molecular Structure; Phenanthrenes; Phenylpropionates; Plant Extracts; Plant Roots; Reference Standards; Salvia miltiorrhiza; Spectrometry, Mass, Electrospray Ionization

A sensitive and specific HPLC-UV method was developed for the simultaneous determination of major active components of danshen in rat plasma. Both water-soluble and lipid-soluble compounds were included, i.e. danshensu, salvianolic acid B and tanshinone IIA. Protocatechuic aldehyde and diazepam were used as internal standards. The chromatographic separation was achieved on a reversed-phase C(18) column by gradient elution using acetonitrile and 0.025% (v/v) phosphoric acid solution as mobile phase, at a flow rate of 1.0 mL/min. Salvianolic acid B, danshensu and internal standards were detected at 281 nm, while the detection of tanshinone IIA was carried out at 272 nm. All calibration curves showed good linearity (r(2) > 0.999) within test ranges. The limit of detection and the limit of quantification for danshensu, salvianolic acid B and tanshinone IIA in plasma were 0.065, 0.043, 0.022, 0.131, 0.085 and 0.044 microg/mL, respectively. This is the first report on the determination and pharmacokinetic study of danshensu, salvianolic acid B and tanshinone IIA in rat plasma and the results indicated that this method was reliable for the determination of the major active components of danshen in rat plasma.

Topics: Abietanes; Animals; Benzofurans; Calibration; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Hydrophobic and Hydrophilic Interactions; Lipids; Molecular Structure; Phenanthrenes; Phenanthrolines; Rats; Rats, Sprague-Dawley; Reference Standards; Reproducibility of Results; Salvia miltiorrhiza; Sensitivity and Specificity; Spectrophotometry, Ultraviolet; Water

To provide some evidence for breeding excellent lines of Salvia miltiorrhiza.. Contents of tanshinone II(A), cryptotanshinone, salvialic acid A and salvianolic acid B in root of S. miltiorrhiza from different populations were determined by HPLC. Total tanshinone and total salvianolic acids were determined by spectrophotometry.. The biomass of individual plant from Zhongjiang of Sichuan province, content of tanshinone II(A), from Shanxi province, cryptotanshinone and total tanshinone from Zhongjiang of Sichuan province, salvialic acid A of High-Stem cultivation from Hebei province, salvianolic acid B and total salvianolic acids of tetroploid were higher than the other samples, respectively. With the value of biomass of individual plant multiplying contents of every active components as indicative constituents, the multiplying value from Zhongjiang of Sichuan province was higher than the other samples.. With biomasses and effective components as indicative constituents, it suggested that S. miltiorrhiza from Zhongjiang of Sichuan province was a better derivative material.

Topics: Abietanes; Benzofurans; Biomass; Caffeic Acids; China; Chromatography, High Pressure Liquid; Ecosystem; Lactates; Phenanthrenes; Plant Roots; Plants, Medicinal; Salvia miltiorrhiza; Spectrophotometry, Ultraviolet

Rapid nondestructive determination of salvianolic acid B and tanshinone IIA in Radix Salviae Miltiorrhizae with near-infrared reflectance spectroscopy.. A quantitive model was built up with near-infrared diffuse reflectance spectroscopy.. The RMSEP in quantitative calibration model for salvianolic acid B and tanshinone IIA were 0.259 and 0.0232 respectively.. NIR technique can dispose the samples without complicated pretreatment. You can achieve the results rapidly and correctly. It owns many remarkable advantages that cannot be displayed by traditional analysis methods. It is qualified to rapidly analyze traditional Chinese medicine whose components are complex. NIR can control the quality in production process of traditional Chinese medicine.

Topics: Abietanes; Benzofurans; Electronic Data Processing; Least-Squares Analysis; Models, Theoretical; Phenanthrenes; Plant Roots; Plants, Medicinal; Quality Control; Reproducibility of Results; Salvia miltiorrhiza; Spectroscopy, Near-Infrared

Tanshinone derivative compounds, isolated from Salvia miltiorrhiza Bunge (Labiatae), have been reported as microtubule inhibitors with antimitotic activity. In this study, we examined the growth-inhibiting and differentiation-inducing effect of these compounds on human leukemic HL-60 cells. The expression of protein kinase C (PKC) and proto-oncogenes in 278E-treated cells was also assessed. All tanshinone derivative compounds exhibited growth-inhibitory effects on HL-60 cells, but only 278E induced cell differentiation. Morphological observation of 278E-treated HL-60 cells showed a greater percentage of monocytes and macrophages (Mo/Mphi). Treatment with 5 microg/ml 278E resulted in a marked increase in the percentages of superoxide-producing (up to 95.5+/-1.8%) and non-specific esterase-positive cells (up to 80.3+/-9.1%). The differentiated cells also expressed cell surface antigens characteristic of Mo/Mphi, including CD11b, CD14 and CD68. Neither cellular changes in isozymes of PKC nor translocation of these isozymes from cytosol to cell membrane were seen in 278E-treated HL-60 cells. 278E caused a downregulation of c-myc as well as an up-regulation of c-fms, c-jun and c-fos.

Topics: Abietanes; Antineoplastic Agents; Benzofurans; Cell Differentiation; Cell Proliferation; Drugs, Chinese Herbal; Esterases; HL-60 Cells; Humans; Isoenzymes; Monocytes; Phenanthrenes; Protein Kinase C; Proto-Oncogene Mas; Proto-Oncogene Proteins; Salvia miltiorrhiza; Superoxides