Understanding the Multitarget Pharmacological Mechanism of the Traditional Mongolian Common Herb Pair GuangZao-RouDouKou Acting on Coronary Heart Disease Based on a Bioinformatics Approach

摘要

GuangZao and RouDouKou (Fructus Choerospondiatis and Nutmeg, FCN) are one of the most common herb pairs in traditional Mongolian medicine for the treatment of coronary heart disease (CHD). However, evidence for the protective effect of FCN is limited, and its underlying mechanism of action remains unclear. The present study employed a network pharmacology approach to identify the potentially active ingredients and synergistic effects of the herb pair FCN as traditional Mongolian medicine. We predicted the targets of all available FCN ingredients with PharmMapper, SWISS, and SuperPred Server and clustered CHD-related targets from the DrugBank and the OMIM database. We also evaluated the links between herbal ingredients and pharmacological actions to explore the potential mechanism of action of FCN. We found that FCN targets a network of CHD-related key processes, including stress responses, cell adhesion and connections, angiogenesis, cell apoptosis and necrosis, the endocrine system, inflammatory and immune responses, and other biological processes. To confirm the predicted results, we investigated the protective effect of FCN on isoproterenol- (ISO-) induced myocardial ischemia in rats. Pathological assessment indicated that FCN inhibits apoptosis and inflammatory responses involving the myocardium. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analyses demonstrated the therapeutic effects of FCN on ISO-induced myocardial ischemia rats, possibly via regulating stress and inflammatory responses and inhibiting cardiomyocyte apoptosis. The findings of the present study indicate that bioinformatics combined with experimental verification provide a credible and objective method to elucidate the complex multitarget mechanism of action of FCN.