Exploring the effects and mechanisms of Guizhigancao Decoction on heart failure using an integrated approach based on experimental support and network pharmacology strategy

基于实验支持和网络药理学策略的综合方法,探讨桂枝甘草汤对心力衰竭的影响及其机制

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Abstract

BACKGROUND AND AIM: HF (Heart Failure) is the leading cause of mortality and is a significant clinical problem affecting millions of patients worldwide. To date, the mechanisms of HF remain largely elusive. The effective treatments contributing to HF remain incompletely understood. Therefore, the development of an effective strategy for HF is urgently needed. EXPERIMENTAL PROCEDURE: In the present study, we devoted to investigating the effective treatments and sought to systematically decipher the related molecular mechanisms of Guizhigancao Decoction (GZGCD, Cinnamomum cassia Presl and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle) for treating HF. We examined the therapeutic effect of GZGCD on HF in vivo. An integrative approach combining biomarker examination, echocardiography, myocardial fibrosis and cardiac apoptosis condition using Masson and TUNEL staining was performed to assess the efficacy of GZGCD against HF. Subsequently, comprehensive network pharmacology analyses were performed to explore the mechanisms involved in GZGCD therapeutic effects on HF. RESULTS AND CONCLUSIONS: The results showed that GZGCD could reverse cardiac function in rats with HF by reducing NT-proBNP, increasing EF, decreasing LVESV, LVEDV, LVIDs, LVIDd, increasing running time, and ameliorate myocardial collagen fiber hyperplasia and cardiomyocyte apoptosis. We showed that GZGCD might contribute to HF treatment via oxidative related pathways through bioinformatics. Eventually, promising compound quercetin in GZGCD for HF therapeutics was proposed in database-based analysis. Collectively, our findings indicate that GZGCD has a treatment effect on HF. We proposed that GZGCD might contribute HF treatment via oxidative response-related pathways.

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