Exploration of the Potential Bioactive Compounds and Functional Mechanism of Chaihu Sanshen Capsule in Ameliorating Myocardial Ischaemia–Reperfusion Injury: A Serum Pharmaco-Chemistry With Network Pharmacology Analysis

Abstract

Previous studies have shown the potential of Chaihu Sanshen capsule (CHSSC) to ameliorate myocardial ischemia-reperfusion injury (MIRI), but there is yet no corresponding research on its chemical ingredients and multi-target action network. The study aims to identify the chemical composition and potential bioactive compounds of CHSSC and elucidate its underlying mechanisms in MIRI treatment. Ultra-high-performance liquid chromatography-Q exactive focus-mass spectrometry was used to analyse the chemical composition and potential bioactive compounds of CHSSC. The active compounds were analysed via network pharmacology to identify the core targets and pathways. The oxygen–glucose deprivation/reoxygenation (OGD/R) H9C2 cell model and MIRI rat model were established, followed by intervention with CHSSC. TUNEL, flow cytometry and western blotting assays were used to observe the effects of CHSSC on apoptosis, pyroptosis and the PI3K/AKT/p53 signalling pathway, respectively, of cardiomyocytes. In all, 1587 compounds were detected in CHSSC, of which 106 were absorbed into the bloodstream, mainly comprising flavonoids, terpenoids, alkaloids, organic acids, coumarins and phenols. CHSSC primarily targeted TP53, AKT, STAT3, HSP90AA1 and MAPK and involved the regulation of p53, PI3K/AKT, JAK2/STAT3 and MAPK signalling pathways; however, these predicted targets have not yet been validated by confirmatory binding assays. In vitro experiments showed that CHSSC reduced the apoptosis and pyroptosis rates of OGD/R H9C2 cells. In vivo, CHSSC ameliorated myocardial injury in MIRI rats, decreased the cardiomyocyte apoptosis rate, increased PI3K and AKT phosphorylation and inhibited p53 phosphorylation. In conclusion, this study elucidated the potential bioactive compounds and multi-targets action network of CHSSC in mitigating MIRI, and verified that the effects of CHSSC on MIRI are link to the PI3K/AKT/p53 signalling pathway.