salvianolic-acid-a and lithospermic-acid

The quality of Chinese medicine (CM) has being an active and challenging research area for CM. Prof. Chang-Xiao Liu et al first proposed the concept of quality marker (Q-Marker) for the quality evaluation and control on CM. This article describe the exploratory studies of Q-Marker in salvianolic acids for injection (SAI) based on this new concept.. This study was designed to screen Q-Marker of SAI and establish its quality control method based on the concept of CM Q-Marker.. Based on the concept of CM Q-Marker, the SAI was investigated for the identification of chemical components and their sources. The pharmacological effects on cerebral ischemia and reperfusion induced injury in rats were also investigated. Furthermore, the target cell extracts and pharmacokinetic studies were conducted to screen Q-Markers. Finally, the fingerprints and determination based on Q-Markers were established to assess the quality of SAI more effectively.. Overall, 20 constituents in SAI were identified. It was found that salvianolic acid B (SA-B), rosmarinic acid (RA), lithospermic acid (LA), salvianolic acid D (SA-D) and salvianolic acid Y (SA-Y) are major chemical components of SAI. Based on chemical components identifications, analysis of their sources, target cell extracts and pharmacokinetic studies, four phenolic acids, namely SA-B, RA, LA and SA-D, were screened and determined as effective Q-Markers of SAI.. This study demonstrated that the described method is a powerful approach for detecting Q-Markers, which can be used as control index for the quality assessment of CM.

Topics: Alkenes; Animals; Benzofurans; Biomarkers; Brain; Brain Ischemia; Cell Line; Cinnamates; Depsides; Drugs, Chinese Herbal; Endothelium, Vascular; Injections; Interleukin-1; Interleukin-6; Male; Polyphenols; Quality Control; Rats, Sprague-Dawley; Rosmarinic Acid; Superoxide Dismutase

Salvianolic acid A (Sal A) was considered to be the compound with highest activity in Salvia miltiorrhiza (danshen). Due to its low content in raw materials, many studies reported its preparation from salvianolic acid B (Sal B). However, the process of this transformation is still unknown. Our objective was to find the chemical change of the transformation from Sal B to Sal A. The results showed that Sal B was hydrolyzed to lithospermic acid (LA) first, and the latter was transformed into Sal A in thermal aqueous solution. The radical scavenging ability of Sal A, Sal B, and LA was tested through DPPH, and Sal A showed higher radical elimination ability compared to Sal B and LA. In vitro liver damage was induced by CCl4 in human hepatic WRL68 cell line. Sal A, Sal B, and LA showed liver protective ability in a dose-dependent manner, while Sal A possessed a much higher ability compared to Sal B and LA.

Topics: Antioxidants; Benzofurans; Biphenyl Compounds; Caffeic Acids; Carbon Tetrachloride; Cell Line; Chemical and Drug Induced Liver Injury; Depsides; Drugs, Chinese Herbal; Hot Temperature; Humans; In Vitro Techniques; Lactates; Liver; Phytotherapy; Picrates; Salvia miltiorrhiza; Water

Buglossoides purpureocaerulea is a little-known plant used in the folk tradition for the preparation of a decoction in Sud, Italy, where it is appreciated for its beneficial effects on liver diseases. These properties may be due to the presence of antioxidant compounds. This study presents the phenolic characterisation and the antioxidant activity (AA) of B. purpureocaerulea extracts obtained by decoction, ethanol infusion and ethanol and methanol macerations. Total phenols ranged between 69 and 100 mg g(-1 ) dry weight (DW). The main compounds were: rosmarinic acid, caffeic acid, lithospermic acid and salvianolic acid C. The extracts showed a good AA, particularly high for the decoction (142-283 µmol TE g(-1) DW; TE, Trolox equivalent) and ethanol maceration extract (214-364 µmol TE g(-1) DW) when determined by DPPH and ferric reducing antioxidant power test, respectively.

Topics: Alkenes; Antioxidants; Benzofurans; Biphenyl Compounds; Boraginaceae; Caffeic Acids; Cinnamates; Depsides; Free Radical Scavengers; Picrates; Plant Extracts; Polyphenols; Rosmarinic Acid

When herbal products are used in combination therapy with drugs, alterations in pharmacokinetics, pharmacodynamics, and toxicity can result. Many active components of herbal products are organic anions, and human organic anion transporter 1 (hOAT1, SLC22A6), hOAT3 (SLC22A8), and hOAT4 (SLC22A11) have been identified as potential sites of drug-drug interactions. Therefore, we assessed the effects of lithospermic acid (LSA), rosmarinic acid (RMA), salvianolic acid A (SAA), salvianolic acid B (SAB), and tanshinol (TSL), components of the herbal medicine Danshen, on the function of these transporters. Kinetic analysis demonstrated a competitive mechanism of inhibition for all five. K(i) values (µM) were estimated as 20.8 ± 2.1 (LSA), 0.35 ± 0.06 (RMA), 5.6 ± 0.3 (SAA), 22.2 ± 1.9 (SAB), and 40.4 ± 12.9 (TSL) on hOAT1 and as 0.59 ± 0.26 (LSA), 0.55 ± 0.25 (RMA), 0.16 ± 0.03 (SAA), 19.8 ± 8.4 (SAB), and 8.6 ± 3.3 (TSL) on hOAT3. No significant inhibition of hOAT4 activity by TSL was observed. Using published human pharmacokinetic values, unbound C(max)/K(i) ratios were calculated as an indicator of in vivo drug-drug interaction potential. Analysis indicated a strong interaction potential for RMA and TSL on both hOAT1 and hOAT3 and for LSA on hOAT3. Thus, herb-drug interactions may occur in vivo in situations of co-administration of Danshen and clinical therapeutics known to be hOAT1/hOAT3 substrates.

Topics: Animals; Benzofurans; Caffeic Acids; CHO Cells; Cinnamates; Cricetulus; Depsides; Drugs, Chinese Herbal; HEK293 Cells; Herb-Drug Interactions; Humans; Lactates; Organic Anion Transport Protein 1; Organic Anion Transporters, Sodium-Independent; Phenanthrolines; Rosmarinic Acid; Salvia miltiorrhiza

To study the chemical changes of salvianolic acid B and lithospermic acid of Salvia miltiorrhiza under the conditions of high temperature and high pressure and explore the reaction mechanism.. S. miltiorrhiza extracts, salvianolic acid B and lithospermic acid were put in the reactor under the conditions of high temperature and high pressure (120 degrees C, 0.2 MPa), and the chemical changes and stability was studied.. Salvianolic acid A was the primary product in salvianolic acid B and lithospermic acid's conversion process, and lithospermic acid was an intermediate in the conversion process of salvianolic acid B. Compared with salvianolic acid B, lithospermic acid could convert into more salvianolic acid A and fewer other products in the same conditions. Salvianolic acid A was not stable under the conditions of high temperature and high pressure, and could sequentially convert into other small molecules.. Referring to the chemical conversion of salvianolic acid B and lithospermic acid, a method of large-scale preparation of salvianolic acid A can be developed.

Topics: Benzofurans; Caffeic Acids; Depsides; Hot Temperature; Lactates; Pressure; Salvia miltiorrhiza

Salvianolic acid A, salvianolic acid B, danshensu, protocatechuic aldehyde, rosmarinic acid and lithospermic acid are the six major active constituents in Danshen injection. In this study, a rapid, sensitive and specific liquid chromatographic-electrospray ionization-mass spectrometry method for the simultaneous quantitative determination of these compounds in rat plasma was developed. After a single step of liquid-liquid extraction with ethyl acetate, they were eluted by a Hypersil C18 column (5 µm, i.d. 4.6 × 200 mm) within 4 min with a mobile phase consisting of acetonitrile and 0.1% formic acid water solution (35:65, v/v). The assay was linear in the concentration range of 0.05-10 µg mL(-1). Absolute recoveries were above 60%. The precisions and accuracies determined within three consecutive days were within acceptable limits. The method was successfully applied to a pharmacokinetic study in rats after an intravenous administration of Danshen injection.

Topics: Animals; Benzaldehydes; Benzofurans; Caffeic Acids; Catechols; Chromatography, High Pressure Liquid; Chromatography, Liquid; Cinnamates; Depsides; Drug Stability; Drugs, Chinese Herbal; Injections, Intravenous; Lactates; Liquid-Liquid Extraction; Male; Mass Spectrometry; Plant Preparations; Rats; Reference Standards; Rosmarinic Acid; Salvia miltiorrhiza; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization

An improved everted gut sac method was applied to the study of prescription compatibility effect on the major components in Danshen extracts. With the separation and detection by HPLC-ECD, 5 major peaks could be detected in intestinal absorbed solution after prescription administration. Following the identification by HPLC-MS/MS, peak 2, 3, 4, and 5 were rosmaric acid, lithospermic acid, salvianolic acid B, and salvianolic acid A, respectively, which also confirmed with reference standards of those components. Through paralleling substance identification, peak 2, 3, 4, and 5 could be found as the major components in Danshen extracts, except Salvianolic acid E which is undetectable in intestinal solution. The contents of peak 2, 3, and 4 did not show difference before and after compatible prescription administrated, where the peak 5 had a significant increase in the same process. Those results revealed that peak 5, salvianolic acid A, might lead to an increasing pharmacological effect after prescription compatibility.

Topics: Animals; Benzofurans; Caffeic Acids; Chromatography, High Pressure Liquid; Depsides; Drugs, Chinese Herbal; In Vitro Techniques; Intestinal Absorption; Lactates; Male; Plants, Medicinal; Rats; Rats, Wistar; Salvia miltiorrhiza; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

A rapid, sensitive and specific isocratic liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the simultaneous quantitative determination of magnesium lithospermate B (MLB), rosmarinic acid (RA), and lithospermic acid (LA) in beagle dog serum, with silibinin as internal standard. The serum samples were treated by liquid-liquid extraction and analyzed using LC/MS/MS with a TurboIonSpray source. A short run-time (3 min) fulfilled the need for monitoring serum levels of MLB, RA, and LA in large-scale studies. The calibration curves for MLB, RA, and LA were linear over the ranges 8-2048, 4-1024, and 4-1024 ng/mL, respectively, with coefficients of correlation >0.999. The intra- and inter-day precision (CV) of analysis was <10%, and accuracy ranged from 90-104%. This quantitation method was successfully applied to a pharmacokinetic study of salvianolate administrated by intravenous infusion with dosage of 6 mg/kg in beagle dogs.

Topics: Animals; Antioxidants; Benzofurans; Caffeic Acids; Chromatography, High Pressure Liquid; Cinnamates; Depsides; Dogs; Drugs, Chinese Herbal; Free Radical Scavengers; Injections, Intravenous; Lactates; Phenanthrolines; Reproducibility of Results; Rosmarinic Acid; Salvia miltiorrhiza; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization