Abstract

Phellodendrine is a Phellodendri Cortex-derived isoquinoline alkaloids, has been shown to have various activities, especially hypoglycemic effect in mice, predicting its medicinal value on diabetes mellitus. To further understand the pharmacological effect of phellodendrine on diabetes mellitus, network pharmacological techniques have been used to elaborate the involved mechanisms. 84 common target molecules were screened, based on the chemical structure of phellodendrine molecule and disease database. These proteins were enriched in insulin resistance, insulin secretion and inflammatory response, mainly focus on the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, mitogen-activated protein kinase signaling pathway and interleukin-17 signaling pathway. Moreover, enrichment analysis suggested that the targets of phellodendrine such as phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha and mitogen-activated protein kinases 8 were associated with coronavirus disease 2019. To verify the results, molecular docking technique was used to evaluate the interaction between phellodendrine and key targets in the signaling pathway. The calculated binding energy indicates that phellodendrine can form stable complex with insulin receptor, mitogen-activated protein kinases 8, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha and glycogen synthase kinase 3 beta. These data suggest that phellodendrine should be beneficial for treatment of diabetes mellitus.