Uncovering the molecular mechanisms of Ilex pubescens against myocardial ischemia-reperfusion injury using network pharmacology analysis and experimental pharmacology. (10th January 2022)

• Record Type: Journal Article
• Authors: Zheng, Yuan; Chen, Sixuan; Yang, Ying; Li, Xuping; Wu, Junxuan; Liu, Jiaming; Wang, Yuanping; Qi, Xiaoxiao; Wang, Ying; Liu, Zhongqiu; Wu, Peng; Cheng, Yuanyuan
• Is Part Of: Journal of ethnopharmacology. Volume 282(2021)
• Publication Date: 2022-01-10
• Subjects: Ilex pubescens, myocardial ischemia-reperfusion injury -- Network pharmacology -- HSP90AA1 -- ESRα -- Estrogen signaling pathway; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2021.114611
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Ilex pubescens ( I. pubescens), has been widely used to treat cardiovascular disease (CVD) in South China. Several studies have revealed aspect of its phytochemistry and pharmacological activities in cardiovascular diseases, but its active compounds and mechanisms of action are still unclear. The aim of this study was to search for the active compounds and the pharmacological mechanisms of I. pubescens for myocardial ischemia-reperfusion injury (MI/RI) by an integrative pharmacology-based investigation. Materials and methods: The main targets of compounds in I. pubescens were predicted using the TargetNet webserver (http://targetnet.scbdd.com ). The network between compounds and predicted targets related to MI/RI and compounds was constructed. Functional enrichment analysis was performed to investigate the specific functions and pathways involved in the candidate I. pubescens targets acting on MI/RI, which were further validated by in vitro and in vivo experiments. Results: A total of 191 targets were predicted for 64 chemical compounds in I. pubescens . Following Venn's analysis, we found that 38 candidate targets of I. pubescens were associated with protective effects against MI/RI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that these targets were related to estrogen signaling pathway. Importantly, the cardioprotective effects of I. pubescens and its active compounds were evaluated and the regulatory effects on key targets of heat shock protein 90 alpha family class A member 1 (HSP90AA1) and Estrogen receptor 1 (ESRα) in estrogen signaling pathway were validated in vitro and in vivo . Conclusion: Our discoveries revealed that I. pubescens ameliorated MI/RI by regulating HSP90AA1 and ESRα in estrogen signaling pathway. Graphical abstract: Image 1 Highlights: I. pubescens has cardioprotective effects against myocardial ischemia-reperfusion injury. 38 candidate targets of I. pubescens were associated with the protective effects on MI/RI . I. pubescens and active compounds reduced the apoptosis of cardiomyocytes via regulation of HSP90AA1 and ESRα.