Integrating network pharmacology and experimental evidence to decipher the cardioprotective mechanism of Yiqihuoxue decoction in rats after myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: "Qi deficiency and blood stasis" syndrome is one of the most common syndromes treated with Traditional Chinese Medicine among ischemic heart disease (IHD) patients in clinic. As a Chinese herbal formula with the function of tonifying Qi and activating blood, Yiqihuoxue Decoction (YQHX) has been frequently proven to be effective in the clinical treatment of IHD. AIM OF THE STUDY: The cardioprotective mechanisms of YQHX in treating ischemic heart disease were investigated, with emphasis on the key targets and pathways. MATERIALS AND METHODS: In the present study, the potential targets of compounds identified in YQHX were predicted using PharmMapper, Symmap, and STITCH databases, and a "herb-compound-target" network was constructed using Cytoscape. Subsequently, the GO and KEGG functional enrichment analyses were analyzed using the DAVID database. Furthermore, a protein-protein interaction network was constructed using STRING to obtain the key target information. Besides, we used a myocardial ischemia rat model to investigate the cardioprotective effects of YQHX. Transmission electron microscopy and Western blotting were used to observe apoptotic bodies and confirm protein expressions of key candidate targets, respectively. RESULTS: Network pharmacology showed that a total of 141 potential targets were obtained from these databases. The functional analysis results revealed that the targets of YQHX were largely associated with apoptosis, and the PI3K-AKT and MAPK pathways might represent key functional pathways. The hub genes of network include ALB, TP53, AKT1, TNF, VEGFA, EGFR, MAPK1, CASP3, JUN, FN1, MMP9, and MAPK8. In vivo, YQHX significantly improved cardiac function and suppressed apoptosis in ischemic rat myocardium. Furthermore, YQHX could significantly upregulate Nrf2 and HO-1 expression, and inhibit JNK phosphorylation. CONCLUSIONS: Based on network pharmacology and experimental evidence, this study proves that the cardioprotective effects and mechanisms of YQHX depend on multi-component, multi-target, and multi-pathway. In particular, YQHX exerts anti-apoptotic effects potentially by regulating the Nrf2/HO-1 and JNK-MAPK pathways.

The clinical efficacy and safety of the Chinese herbal medicine Astragalus (Huangqi) preparation for the treatment of acute myocardial infarction: A systematic review of randomized controlled trials.

BACKGROUND: In recent years, with the enormous advances in the field of cardiac intervention technology, the survival rate of patients with acute myocardial infarction (AMI) has been improved significantly. However, the risk of arrhythmias and heart failure remains very high in AMI patients for long-term prognosis. Chinese herbal medicine (CHM) is more and more used in the treatment of AMI because of its good curative effect and less side effects. The target of this research is to analyze the efficacy and safety of Astragalus (Huangqi) preparation in the treatment of AMI by meta-analysis and also to provide a better evidence for clinical practice. METHODS: Seven databases will be searched in this study: The Cochrane Library, PubMed, Web of Science, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (CSJD), the Chinese Biomedical Literature Database (CBM), and Wanfang DATA. The following search terms will be used: (Huangqi OR Huang Qi OR Astragalus OR radix astragali) AND (acute myocardial infaction OR myocardial infaction OR AMI) AND (randomized controlled trial OR RCT OR randomized). No language limitations and the searches will be conducted up to March, 2019. INCLUSION CRITERIA: randomized controlled trial (RCT) of Astragalus (Huangqi) preparation in patients with AMI. Main outcome measures will be left ventricular end systolic volume (LVESV), left ventricular end diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), recanalization rate, mortality rate, incidence of reperfusion arrhythmias, postinfarction angina pectoris, and re-infarction rate. Secondary outcome indicators were the incidence of adverse reactions and the effective rate of traditional Chinese medicine (TCM) treatment. Two independent reviewers will filter the literature and extract data which based to the Cochrane manual. The relevant data, including bias risk assessment, data synthesis, subgroup analysis, meta-analysis, and final meta-analysis, will be analyzed with RevMan 5.3 software. The funnel diagram will be used to evaluate the reported deviation, and the Egger test will be used to evaluate the symmetry of the funnel graph. RESULTS: This systematic review study will provide a clear basis for evaluating the efficacy and safety of Astragalus (Huangqi) preparation with the treatment of AMI. CONCLUSION: This study will provide an up-to-date evidence for evaluating the efficacy and safety of Astragalus (Huangqi) preparation. PROSPERO REGISTRATION NUMBER: CRD42019124843.