Revealing the mechanism of Gualou-Xiebai against myocardial ischemia based on network pharmacology and energy metabolism strategies.

Abstract

Trichosanthes kirilowii-Allium macrostemon (Chinese name Gualou and Xiebai, GLXB), a classical herb pair, has significant clinical efficacy in the treatment of myocardial ischemia (MI). In this study, network pharmacology combined with RNA-seq strategy was employed to predict the targets and pathways of GLXB for MI. GLXB significantly modulated signaling pathways related to the pathology of MI, such as anti-inflammatory and anti-apoptotic signaling pathways such as WNT, PI3K/AKT, and AMPK. GSEA showed that GLXB administration downregulated these key pathways. In addition, Metabolomic analysis demonstrated that GLXB treatment reversed metabolic disorder. Integrative analysis demonstrated three key metabolites (pyruvate, lactate, and palmitate) and three differential genes (Pck1, Cdo1, and Cth) that affected glycolysis or gluconeogenesis and cysteine and methionine metabolism. The results of molecular docking showed that chrysin-7-O-glucuronide and diosmetin-7-O-rutinoside may be the crucial components that exert myocardial protective activity. Western blot showed that GLXB administration reversed the expression levels of Pck1, Cdo1, Cth, Alb, Bcl2, and Ccnd1. This study has elucidated that GLXB could alleviate MI in rats by modulating WNT and PI3K/AKT signaling pathways, thereby reducing inflammation and apoptosis as well as improving energy metabolism.