Network pharmacology-based study of the mechanisms of action of anti-diabetic triterpenoids from Cyclocarya paliurus

Abstract

Diabetes is a complex illness requiring long-term therapy. Cyclocarya paliurus, a recently confirmed new food resource, shows significant hypoglycemic and hypolipidemic effects in type II diabetes. Triterpenoid saponins are considered as the effective medicinal components of C. paliurus and are useful for the treatment of diabetes mellitus. However, little is known regarding their specific mechanism of actions. In this study, we used active ingredient screening and target prediction techniques to determine the components of C. paliurus responsible for its anti-diabetic effects as well as their targets. In addition, we used bioinformatics technology and molecular docking analysis to determine the mechanisms underlying their anti-diabetic effects. A total of 39 triterpenes were identified through a literature search and 1 triterpene compound by experiments. In all, 33 potential target proteins associated with 36 pathways were predicted to be related to diabetes. Finally, 7 compounds, 15 target proteins, and 15 signaling pathways were found to play important roles in the therapeutic effects of C. paliurus against diabetes. These results provide a theoretical framework for the use of C. paliurus against diabetes. Moreover, molecular docking verification showed that more than 90% of the active ingredients had binding activity when tested against key target proteins, and a literature search showed that the active ingredients identified had anti-diabetic effects, indicating that the results were highly reliable.