ABSTRACT
This study establishes a quantitative analysis of multi-components by single marker (QAMS) method for the simultaneous determination of gallic acid, sodium danshensu, protocatechuic acid, protocatechuic aldehyde, vanillin, rosmarinic acid, salvianolic acid B, eugenol, cryptotanshinone and tanshinone IIA in Guanxinshutong capsules (Bambusae Concretio Silicea, Salvia miltiorrhiza, clove, borneol, Bambusae Concretio Silicea) by HPLC. Sample was loaded onto an Agilent C18 (ZORBAX Extend-RP C18, 250 mm × 4.6 mm, 5 µm) column and eluted with methanol-0.4% aqueous formic acid solution as a flow phase gradient, flow speed 1.0 mL·min-1, detection wavelength 280 nm, column temperature 35 ℃ and sample intake of 5 µL. Using protocatechuic acid as the internal reference, a relative correction factor was calculated and the durability was investigated, and the content of 10 components was calculated by QAMS and external standard method (ESM). The results show that the specificity, linear relationship, precision, repeatability, and stability of the 10 components were good. The average recovery was 98.20%-103.47% and RSD was 1.26%-2.84%. The relative positive factors and contents of the other nine components were calculated as gallic acid (0.759, 227.381), sodium tanshinol (3.630, 3.283), protocatechualdehyde (0.185, 0.150), vanillin (0.532, 65.213), rosmarinic acid (4.240, 1.035), salvianolic acid B (3.245, 18.204), eugenol (1.729, 9.265), cryptotanshinone (0.691, 1.449), and tanshinone ⅡA (0.702, 1.939). The results of QAMS were consistent with ESM analysis, and the relative error was between -3% and 3%. This method is stable and reliable, and can be used for the determination of 10 components in Guanxinshutong capsules.
ABSTRACT
OBJECTIVE: To explore the"multi-component, multi-target, multi-pathway" network regulation mechanism of Guanxinshutong caspules (GXST) in treatment of coronary heart disease by network pharmacology method. METHODS: The chemical components of GXST were identified based on liquid chromatography-mass spectrometry (LC-MS), and the oral bioavailability (OB)≥30% and drug likeness (DL)≥0.18 were used as the screening conditions for obtaining active molecular compounds. The targets related to the active compounds were predicted through the Traditional Chinese Medicine Systems Pharmacology database (TCMSP).The relevant targets of coronary heart disease were searched through literature mining and multiple databases and compared with the predicted component targets. Finally, the targets were introduced into the Molecule Annotation System 3.0 (MAS 3.0)to analyze the main biological pathways. RESULTS: Forty-three compounds were identified in GXST based on LC-MS technology and 10 main active compounds were determined through OB and DL screening, such as ellagic acid, cryptotanshinone, and tanshinone. These components affected 26 key targets, such as CLP, LDLR, TNF, et al, and 49 KEGG pathways were involved (P<0.05). CONCLUSION: GXST produces therapeutic effect for coronary heart disease mainly through the TGF-beta, T cell receptors, and MAPK signaling pathway.This study further reveals the characteristics of the multi-component, multi-target and multi-pathway of GXST, and lays a certain foundation for further elucidation of the mechanism of GXST in the treatment of coronary heart disease.
ABSTRACT
Guanxinshutong capsule (GXSTC) is an effective and safe traditional Chinese medicine used in the treatment of cardiovascular diseases (CVDs) for many years. However, the targets of this herbal formula and the underlying molecular mechanisms of action involved in the treatment of CVDs are still unclear. In the present study, we used a systems pharmacology approach to identify the active ingredients of GXSTC and their corresponding targets in the calcium signaling pathway with respect to the treatment of CVDs. This method integrated chromatographic techniques, prediction of absorption, distribution, metabolism, and excretion, analysis using Kyoto Encyclopedia of Genes and Genomes, network construction, and pharmacological experiments. 12 active compounds and 33 targets were found to have a role in the treatment of CVDs, and four main active ingredients, including protocatechuic acid, cryptotanshinone, eugenol, and borneol were selected to verify the effect of (GXSTC) on calcium signaling system in cardiomyocyte injury induced by hypoxia and reoxygenation. The results from the present study revealed the active components and targets of GXSTC in the treatment of CVDs, providing a new perspective to enhance the understanding of the role of the calcium signaling pathway in the therapeutic effect of GXSTC.
Subject(s)
Animals , Rats , Animals, Newborn , Camphanes , Chemistry , Cardiotonic Agents , Chemistry , Pharmacology , Cells, Cultured , Drugs, Chinese Herbal , Chemistry , Pharmacology , Eugenol , Chemistry , Gene Expression , Hydroxybenzoates , Chemistry , Mass Spectrometry , Models, Biological , Myocytes, Cardiac , Nitric Oxide Synthase Type III , Genetics , Phenanthrenes , Chemistry , Rats, Sprague-Dawley , Receptor, PAR-1 , Genetics , Systems BiologyABSTRACT
Guanxinshutong capsule (GXSTC) is an effective and safe traditional Chinese medicine used in the treatment of cardiovascular diseases (CVDs) for many years. However, the targets of this herbal formula and the underlying molecular mechanisms of action involved in the treatment of CVDs are still unclear. In the present study, we used a systems pharmacology approach to identify the active ingredients of GXSTC and their corresponding targets in the calcium signaling pathway with respect to the treatment of CVDs. This method integrated chromatographic techniques, prediction of absorption, distribution, metabolism, and excretion, analysis using Kyoto Encyclopedia of Genes and Genomes, network construction, and pharmacological experiments. 12 active compounds and 33 targets were found to have a role in the treatment of CVDs, and four main active ingredients, including protocatechuic acid, cryptotanshinone, eugenol, and borneol were selected to verify the effect of (GXSTC) on calcium signaling system in cardiomyocyte injury induced by hypoxia and reoxygenation. The results from the present study revealed the active components and targets of GXSTC in the treatment of CVDs, providing a new perspective to enhance the understanding of the role of the calcium signaling pathway in the therapeutic effect of GXSTC.