3-4-dihydroxyphenyllactic-acid 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

We found that modified Taohong Siwu decoction (MTHSWD) had cardioprotective effects after myocardial ischemia-reperfusion injury. This study was to screen the effective components of MTHSWD that have protective effects on H9c2 cell injury through H

Topics: Animals; Apoptosis; Hydrogen Peroxide; Proto-Oncogene Proteins c-akt; Signal Transduction; Superoxide Dismutase

This study aimed to investigate the active components of Bushen Huoxue Prescriptions (BHP), and further clarify the mechanism by the integration of serum pharmacochemistry and serum pharmacology based on spectrum-effect relationship in vivo. In this paper, the components absorbed into serum were analyzed by ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap-high resolution mass spectrometry (UPLC-Q-Exactive Orbitrap-HRMS). And Müller cells were chosen as target cells to further investigate the mechanism. After cell purification, the well-grown cells were identified by Hematoxylin-eosin staining (HE) staining and immunofluorescence assay, such as glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). The logarithmic phase cells were divided into normal group, model group and 12 BHP groups. The hyperglycemic and hypoxic model was induced by 50 mmol/L glucose and 1 mmol/L sodium disulfite. Enzyme-linked immunesorbnent assay (ELISA) was used to detect the expressions of five factors closely related to DR, named vascular endothelial growth factor (VEGF), hypoxia-inducible factor1-alpha (HIF-1α), protein kinase C-β (PKC-β), angiopoietin-2 (ANG-2) and transforming growth factor-β (TGF-β). Finally, the spectrum-effect relationship was investigated to screen the active components of BHP by partial least squares regression (PLSR). The results showed that 83 metabolic components, containing 30 prototypes and 53 metabolites were found in BHP serum. 12 characteristic common peaks were chosen to establish spectrum-effect relationship. Significantly, all the 12 BHP serum exhibited stronger inhibition on the expression of VEGF, PKC-β, and ANG-2, and the expression of VEGF, PKC-β, ANG-2 was chosen to establish the spectrum-effect relationship in vivo. The results of PLSR revealed that the content of methylation and sulfuration of caffeic acid, dehydroxylation and sulfation of Danshensu, daidzein, O-demethylangolanolin, cryptotanshinone, tanshinone IIA and protopanaxatriol were inversely correlated with VEGF expression of Müller cells; the areas of dihydrocaffeic acid, methylation and sulfuration of caffeic acid, dehydroxylation and sulfation of Danshensu, daidzein, cryptotanshinone, tanshinone IIA were negative correlation with the expression of PKC-β; while the coefficient of hydroxytyrosol sulfation, R-equol, O-demethylangolanolin, dihydrotanshinone IIA, hydrated cryptotanshinone, protopanaxatriol showed negative correlation with th

Topics: Diabetes Mellitus; Diabetic Retinopathy; Humans; Vascular Endothelial Growth Factor A

Fufang Danshen Dripping Pill (FDDP) and Clopidogrel Bisulfate Tablet (CBT) are usually combined for treatment of coronary artery diseases in clinical. To investigate the pharmacokinetic interaction between FDDP and CBT after oral administration of FDDP, CBT and their combination in rats, a novel LC-MS method with segmented scan modes (multiple reaction monitoring and selected ion monitoring) and polarity (positive and negative ionization) was developed. Clopidogrel and the main active ingredients of FDDP, with different chemical and ionization properties, were simultaneously quantified in plasma in a single run. The method was validated in terms of specificity, linearity, precision, accuracy, recovery, matrix effect and stability. As a result, co-administration of FDDP and CBT significantly altered the pharmacokinetic parameters of danshensu, ginsenoside Rb1, dihydrotanshinone I, tanshinone I and tanshinone IIA of FDDP, as well as clopidogrel. Mechanism studies suggested that induction of liver cytochrome P450 isozymes CYP2C11 and CYP3A1 by co-administration, as well as inhibition of carboxyl esterase 1, was partly responsible for FDDP-CBT pharmacokinetic interactions. The developed LC-MS method could be used to simultaneously quantify different types of in vivo analytes in a single run, and the results could be used for clinical medication guidance of FDDP and CBT.

Topics: Abietanes; Administration, Oral; Animals; Aryl Hydrocarbon Hydroxylases; Camphanes; Chromatography, Liquid; Clopidogrel; Cytochrome P-450 CYP3A; Cytochrome P450 Family 2; Drugs, Chinese Herbal; Ginsenosides; Lactates; Linear Models; Male; Panax notoginseng; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Salvia miltiorrhiza; Steroid 16-alpha-Hydroxylase; Tandem Mass Spectrometry

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

Some of the major components of Danshen (Salvia miltiorrhiza), a widely used Chinese herbal medicine rich in phenolic acids, are thermosensitive and may degrade to other phenolic acids during extractions with heating. The chemical profiles of Danshen water-extract may vary with different heat water extraction at different temperatures, affecting the composition and bioactivity of the extracts. In this study, six water-extracts of Danshen obtained from heat reflux water extraction and microwave-assisted extraction with water (MAE-W) at different temperatures were tested for their composition and pharmacological effects. Among these extracts, the third-round MAE-W (100°C) extract had the highest phenolic acids and tanshinones contents, with the strongest antioxidant activity in 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) assay and ferric reducing/antioxidant potential (FRAP) assay. This extract also showed the strongest inhibitory effects on 2,2'-azobis-2-amidinopropane (AAPH)-induced hemolysis in human red blood cells, hydrogen peroxide-induced apoptosis in rat heart H9c2 cells and the highest relaxation effects on rat basilar artery. The antioxidant effects of Danshen water-extracts linearly correlated to their relaxation effects (r=0.895-0.977). Through multiple linear regression analysis, danshensu was found to be the most significant marker in the antioxidant and vasodilation effects of Danshen water-extract, while tanshinone IIA as the marker on hydrogen peroxide-induced apoptosis in rat heart H9c2 cells. Danshensu is, therefore, a useful marker for the quality control of Danshen water-extracts in antioxidant and vasodilation, while tanshinone IIA for anti-apoptotic potential of different extracts.

Topics: Abietanes; Amidines; Animals; Antioxidants; Apoptosis; Basilar Artery; Biphenyl Compounds; Cell Line; Drugs, Chinese Herbal; Erythrocytes; Ferric Compounds; Heart; Hemolysis; Hot Temperature; Humans; Hydrogen Peroxide; Lactates; Phenols; Picrates; Rats; Salvia miltiorrhiza; Vasodilation; Vasodilator Agents

A sensitive and specific liquid chromatography-tandem mass spectrometry method (LC-MS) was developed and validated for the separation and simultaneous determination of danshensu, rosmarinic acid and tanshinone compounds including cryptotanshinone, tanshinone I, dihydrotanshinone I and tanshinone IIA in rat plasma. Chromatographic separation of the analytes was successfully achieved on a C(18) column using a mobile phase composed of acetonitrile-water containing 0.5% glacial acetic acid. This method demonstrated good linearity and did not have endogenous material interfering with the active compounds and I.S. peaks. The limit of quantification of danshensu, rosmarinic acid, cryptotanshinone, dihydrotanshinone I, tanshinone I and tanshinone IIA were 5, 0.75, 0.1, 0.1, 1 and 0.5 ng/mL. The average extraction recoveries of these analytes from rat plasma were all over 60%. The precisions determined from five days were all within 10%. This method has been successfully applied in the simultaneous quantification and the pharmacokinetic studies of these six compounds in animals which were orally administered with danshen preparations.

Topics: Abietanes; Animals; Chromatography, High Pressure Liquid; Cinnamates; Depsides; Drug Stability; Lactates; Male; Phenanthrenes; Rats; Rats, Sprague-Dawley; Rosmarinic Acid; Salvia miltiorrhiza; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization

After oral administration of Salvia miltiorrhiza (Danshen in Chinese), Panax notoginseng (Sanqi in Chinese) and Danshen Sanqi combination suspensions to Beagle dogs, the plasma concentration-time profiles of danshensu, tanshinone II(A), cryptotanshinone, notoginsenoside R1, ginsenoside Rg1 and Rb1 were analyzed by LC-MS/MS. Pharmacokinetic parameters were calculated and analyzed with BAPP 2.0 software. The results showed that the Cmax and AUC of danshensu, notoginsenoside R1, ginsenoside Rg1 and Rb1 in Danshen Sanqi combination group all decreased in comparison with those of Danshen or Sanqi given alone, while the CLz/F and Vz/F increased to some extent. No significant differences of the pharmacokinetics of tanshinone II(A) and cryptotanshinone were observed between groups.

Topics: Abietanes; Administration, Oral; Animals; Area Under Curve; Dogs; Drug Combinations; Drugs, Chinese Herbal; Female; Ginsenosides; Lactates; Male; Panax notoginseng; Phenanthrenes; Plants, Medicinal; Salvia miltiorrhiza

A dynamic continuous ultrasound-assisted extraction with high intensity ultrasonic probe (CUAE-HIUP) combined with solid-phase extraction (SPE) for preconcentration and clean-up of the extract prior to high-performance liquid chromatography (HPLC) determination of the main biological active ingredients, sodium Danshensu and four tanshinones (dihydrotanshione I, tanshinone I, cryptotanshinone and tanshinone IIA) from root of Salvia miltiorrhiza bunge has been developed. An experimental design (Plackett-Burman design, 2(6)x3/16) was used to optimize the CUAE-HIUP procedure and the SPE step. Detection limits of 1.2-4.2 x 10(-6) mg mL(-1) were achieved with the preconcentration efficiency of more than 10-folds by the SPE procedure. The repeatability and within-laboratory reproducibility of the whole process, expressed as relative standard deviations (RSDs), were 1.5-3.6%, 1.6-3.1%, respectively. As compared with the conventional extraction techniques such as room temperature extraction (24 h), Soxhlet (4 h) and even microwave-assisted extraction (2 min), CUAE-HIUP achieved the highest extraction yield (98.9%) and the least amount (10 mL) of solvent compared with the other techniques (16 mL) in only 3 min. The method was successfully applied to the determination of the five biological active ingredients in root of S. miltiorrhiza bunge and Danshen-containing pharmaceutical formulations.

Topics: Abietanes; Chromatography, High Pressure Liquid; Lactates; Phenanthrenes; Salvia miltiorrhiza; Sensitivity and Specificity; Ultrasonics

A selective and sensitive reversed-phase high performance liquid chromatography method was developed and validated for the simultaneous determination of danshensu, ferulic acid, cryptotanshinone, and tanshinone IIA in rabbit plasma using p-hydroxybenzoic acid as internal standard. Liquid-liquid extraction was used for sample preparation. Chromatographic separation was successfully achieved on an Agilent HC-C(18) column using a mobile phase composed of methanol-water (from 20:80 to 80:20, v/v) containing 0.5% (v/v) glacial acetic acid. The mobile phase was employing gradient elution at a flow rate of 1.0 ml/min. The method showed good linearity and no endogenous material interfered with the marked compounds and I.S. peaks. The limit of quantification of danshensu, ferulic acid, cryptotanshinone, and tanshinone IIA were 0.1, 0.03, 0.05, and 0.05 microg/ml, respectively. The average extract recoveries of the four compounds from rabbit plasma were all over 60%. The precisions determined from 5 days were all within 10%. The established method has been successfully applied in the pharmacokinetic study and drug interaction of danshensu, ferulic acid, cryptotanshinone, and tanshinone IIA in rabbits after intravenous administration of danxiongfang, a useful compound preparation of traditional Chinese medicine.

Topics: Abietanes; Animals; Chromatography, High Pressure Liquid; Coumaric Acids; Drug Interactions; Drugs, Chinese Herbal; Lactates; Male; Medicine, Chinese Traditional; Molecular Structure; Phenanthrenes; Rabbits; Reproducibility of Results; Sensitivity and Specificity; Spectrophotometry, Ultraviolet

To study the chemical constituents of Prunella vulgaris.. To separate the constituents of P. vulgaris by using various kinds of chromatography and identify their structures on the basis of spectral analysis.. Seven compounds were isolated from the spikes of P. vulgaris. Their structures were established as autantiamide acetate (1), rhein (2), tanshinone I (3), danshensu (4), stigmast-7, 22-dien-3-one (5), 3, 4, alpha-trihydroxy-methyl phenylpropionate (6), butyl rosmarinate (7).. Compounds 1-4 were isolated from this genus for the first time.

Topics: Abietanes; Amides; Anthraquinones; Chromatography, High Pressure Liquid; Flowers; Lactates; Magnetic Resonance Spectroscopy; Phenanthrenes; Plants, Medicinal; Prunella

To study the effects of tanshinone IIA, danshensu, lithospermate, and protocatechualdehyde on proliferation and procollagen mRNA synthesis of dermal fibroblasts from patients with systemic sclerosis (SSc).. Dermal fibroblasts were obtained from 5 patients with SSc, 2 males and 3 females, and sex and age-matched 5 patients undergoing plastic surgery, cultured, and then co-cultured with tanshinone IIA, danshensu, lithospermate, and protocatechualdehyde respectively. MTT test was used to study the effects of the four constituents on fibroblasts cell proliferation. RT-PCR was used to detect the level of procollagen mRNA expression in the control fibroblasts and in the SSc fibroblasts before and after the addition of the four constituents.. The 4 constituents all suppressed the proliferation of fibroblasts from SSc patients, with tanshinone IIA being the most effective. The 4 constituents remarkably inhibited the mRNA expression of type I and III procollagen of the fibroblasts with tanshinone II A showing the most inhibition effect that reduced the expressions of procollagen I mRNA by 47% and procollagen III mRNA by 45%.. Of the four constituents, tanshinone IIA is the most suppressive effect on the cell proliferation and type I and type III procollagen synthesis of SSc fibroblasts, demonstrating that it has a more antifibrotic effect.

Topics: Abietanes; Benzaldehydes; Catechols; Cell Proliferation; Cells, Cultured; Collagen Type I; Collagen Type III; Drugs, Chinese Herbal; Female; Fibroblasts; Humans; Lactates; Male; Phenanthrenes; Plant Extracts; Procollagen; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Salvia miltiorrhiza; Scleroderma, Systemic; Transcription, Genetic

Using low temperature electron spin resonance (ESR) technique, we found that Salvia miltiorrhiza injection could scavenge the oxygen free radicals generated from ischemia-reperfusion injury in the myocardium as effectively as SOD. Using ESR spin trapping technique we found that one of its effective components, Danshensu, could scavenge superoxide anion free radicals generated from the reaction system of xanthine and xanthine oxidase, and that lipid free radicals generated from lipid peroxidation of myocardial mitochondrial membranes could be scavenged by another effective component, Tanshinone. The membrane fluidity of the mitochondria isolated from the ischemia-reperfused hearts was studied with the ESR spin labelling technique, and the TBA-method was used to detect the lipid peroxidation. It was found that Danshensu could protect the mitochondrial membrane from the ischemia-reperfusion injury and lipid peroxidation.

Topics: Abietanes; Animals; Antioxidants; Drugs, Chinese Herbal; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Intracellular Membranes; Lactates; Lipid Metabolism; Lipid Peroxidation; Mitochondria, Heart; Myocardial Ischemia; Myocardial Reperfusion Injury; Phenanthrenes; Plant Extracts; Rabbits; Salvia miltiorrhiza; Spin Trapping; Superoxides; Thiobarbituric Acid Reactive Substances

Constituents of Radix Salviae Miltiorrhizae and its compound tablets, e.g. tanshinone A, cryptotanshinone, protocatechuic aldehyde and danshensu, were determined by TLC-densitometry. Optimum conditions were selected for constituent extraction, separation and determination. The method is accurate, sensitive and reproducible.

Topics: Abietanes; Benzaldehydes; Catechols; Chromatography, Thin Layer; Densitometry; Drug Combinations; Drugs, Chinese Herbal; Lactates; Phenanthrenes; Phenanthrolines; Plant Extracts; Salvia miltiorrhiza; Tablets