Research Article: Qing-Xin-Jie-Yu granule prevents myocardial infarction-induced apoptosis via inhibition of p38 MAPK pathway
Abstract:
Myocardial infarction (MI) is a leading cause of death globally, and traditional Chinese medicine (TCM) offers therapeutic potential through its multi-targeted approach. This study aims to investigate the protective mechanisms of Qing-Xin-Jie-Yu Granule (QXJYG) against MI.
Network pharmacology was carried out to predict targets and pathways of QXJYG in the treatment of MI. An in vivo mouse model of MI was induced via left anterior descending coronary artery ligation, and hypoxia-induced H9C2 cells were performed as the in vitro model. Cardiac function was assessed by echocardiography, while histological changes were analyzed using HE and Masson's trichrome staining. The positive expression of CD31 was used to assess microvascular density in the hearts of MI mice via immunohistochemistry. Serum levels of superoxide dismutase (SOD), lactate dehydrogenase (LDH), and malondialdehyde (MDA) were evaluated, alongside LDH and MDA in cell culture supernatants. Apoptosis in cardiac tissue was detected by TUNEL staining, while apoptosis in hypoxia-induced H9C2 cells was assessed using Annexin V/PI and Hoechst 33,258 staining. Western blot analysis was conducted to evaluate the protein expression of p-p38 MAPK, p38 MAPK, Bcl-2, Bax in vivo and in vitro experiments.
GO and KEGG analyses suggest that QXJYG affects potential targets related to cellular oxidative stress and apoptosis in MI. In vivo , QXJYG effectively enhanced cardiac function, increased microvessel density, lowered serum LDH and MDA levels, elevated serum SOD levels, and reduced apoptosis in cardiac tissue. It also suppressed the ratio of p-p38 MAPK/p38 MAPK, downregulated Bax protein expression, and upregulated Bcl-2 protein expression in MI mice. In vitro experiments revealed that QXJYG decreased LDH and MDA levels in the culture supernatants, reduced hypoxia-induced apoptosis, inhibited the ratio of p-p38 MAPK/p38 MAPK, decreased Bax protein expression, and enhanced Bcl-2 protein expression. The p38 MAPK inhibitor SB203580 and QXJYG combination more effectively reduced MDA levels and apoptosis in hypoxia-induced H9C2 cells than QXJYG alone.
This study demonstrates that QXJYG exerts cardioprotective effects against MI by improving cardiac function, reducing oxidative stress, and inhibiting apoptosis through the regulation of the p38 MAPK signaling pathway both in vivo and in vitro .
Introduction:
Myocardial infarction (MI) is a leading cause of death globally, and traditional Chinese medicine (TCM) offers therapeutic potential through its multi-targeted approach. This study aims to investigate the protective mechanisms of Qing-Xin-Jie-Yu Granule (QXJYG) against MI.
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