Mechanism of the combination of KuShen and XiYangShen on myocarditis based on network pharmacology and animal experiments

Abstract

Myocarditis is an inflammatory disease of the myocardium and one of the leading causes of sudden death in young people. Its treatment remains challenging. Sophorae Flavescentis Radix (KuShen) and Panacis Quinquefolii Radix (XiYangShen) (the combination of KuShen and XiYangShen is referred to as KX) are the main drugs used to treat myocarditis; however, their active components and mechanisms of action remain unclear. The present study used network pharmacology and animal experiments to analyze the main targets and mechanisms of KX for the treatment of myocarditis. In total, 32 active ingredients, 258 drug targets, 1076 disease targets, and 151 common drug-disease targets were obtained from the initial screening. The drug component–target–myocarditis network, protein-protein interaction (PPI) network and enrichment analysis indicated that ginsenoside Rb1, ginsenoside Re, ginsenoside Rg, oxymatrine, and matrine may be the main active substances of KX. The main effector genes were TNFα, IL-1β, IL-6, IL-17, JAK2, and STAT. The enrichment results indicated that the enriched genes were mainly involved in the IL-17, TNF, and T helper 17 (Th17) cell differentiation signaling pathways. The results from the animal experiments showed evident myocardial damage in the experimental autoimmune myocarditis (EAM) group. In addition, the TNFα, IL-1β, IL-6, and IL-17 levels were significantly increased in the EAM group, while KX ameliorated myocardial injury and inhibited the secretion of inflammatory factors in a dose-dependent manner. Moreover, KX dose-dependently activated the Th17 cell differentiation pathway. Overall, our findings explained the multicomponent, multitarget and multibiological effects of KX for the treatment of myocarditis.