Qianyang yuyin granule ameliorates mitochondrial dysfunction of hypertensive myocardial remodeling.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE Clinical studies have found that Qianyang Yuyin granule (QYYYG), a kind of oral Chinese patent medicine, had definite clinical effect for hypertensive myocardial remodeling. However, the potential mechanism is not entirely clear. AIM OF THE STUDY The purpose of this research was to explore the underlying mechanism QYYYG on the treatment of hypertensive myocardial remodeling. MATERIALS AND METHODS: Analysis the transcriptome data from the NCBI public platform GEO database and our study to explore the key pathological change of myocardial tissues in hypertensive mice and the main pathway of QYYYG in treating hypertensive myocardial remodeling. Network pharmacological analysis was used to predict the potential target of QYYYG. The molecular docking and molecular dynamics simulation was used for molecular binding analysis of specific compounds and target proteins. In the experiment in vivo, the effect of QYYYG on hypertensive myocardial remodeling and myocardial mitochondrial dysfunction in hypertensive mice caused by Ang Ⅱ was estimated. In the experiment in vitro, the Ang Ⅱ-induced myocardial remodeling model in H9c2 cells was constructed, and the effect of QYYYG on ameliorating myocardial remodeling and mitochondrial dysfunction was evaluated. RESULTS: Transcriptome analysis suggested that mitochondrial dysfunction was a key pathological change of myocardial tissues in hypertensive mice, and QYYYG could improve hypertensive myocardial remodeling through enhancing mitochondrial biogenesis to repair myocardial mitochondrial dysfunction. Network pharmacological analysis predicted that SIRT1 was an important potential target of QYYYG in treating hypertensive myocardial remodeling, and basically all the active components, especially quercetin, had a great binding affinity with SIRT1. Experiments in vivo proved that QYYYG had great efficacy hypertensive myocardial remodeling in Ang Ⅱ-treated mice. It was found that QYYYG improved the quality and quantity of mitochondria, and increased SIRT1 levels in myocardial tissue of Ang Ⅱ-treated mice. In Ang Ⅱ-treated H9c2 cells, with intervention of QYYYG, myocardial remodeling and myocardial mitochondrial dysfunction was ameliorated. In addition, QYYYG up-regulated SIRT1 expression and enhanced mitochondrial biogenesis in Ang Ⅱ-treated H9c2 cells. CONCLUSION: This study suggested that mitochondrial dysfunction was an important pathological change of myocardial tissues in hypertensive mice. QYYYG might ameliorate the mitochondrial dysfunction of hypertensive myocardial remodeling through up-regulating SIRT1 expression to enhance the mitochondrial biogenesis.