Antidiabetic effects and mechanisms of Cyclocarya paliurus leaf flavonoids via PIK3CA

Cyclocarya paliurus, a novel functional food resource, exhibits significant hypoglycemic and hypolipidemic effects in treating type II diabetes mellitus (T2DM). Flavonoids are the effective medicinal components of C. paliurus; however, their specific mechanisms in the treatment of T2DM need further evaluation. In this study, in vitro experiments, transcriptomic analysis, network pharmacology, and biolayer interferometry were used to investigate the effects of the total flavonoids of C. paliurus (CTFs) on beta-TC-6 cells and elucidate the underlying mechanisms. Nine flavonoids, including velutin, kaempferide, peonidin, apigenin, pelargonidin, 5,6,7-trihydroxyflavone, tangeretin, laricitrin, and 4 '-methylnaringenin were found to exert antidiabetic effects. The core ingredients of CTFs could directly interact with PIK3CA and modulate gene expression related to the PI3K-AKT signaling pathway, insulin secretion pathway, insulin signaling pathway, and p53 signaling pathway, and promote beta-TC-6 cell proliferation and increase insulin expression. This study provides scientific evidence to support the use of C. paliurus flavonoids in treating T2DM.