A Network Pharmacology Study and In Vitro Evaluation of the Bioactive Compounds of Kadsura coccinea Leaf Extract for the Treatment of Type 2 Diabetes Mellitus

<i>Kadsura coccinea</i> is a traditional Chinese medicine whose roots have long been used to treat various ailments, but little is known about the efficacy of its leaves. In this study, the antidiabetic activity of <i>K. coccinea</i> leaf extract (KCLE) was determined, the main components of KCLE were identified using UPLC-TOF-MS, and network pharmacology and molecular docking were integrated to elucidate the antidiabetic mechanism of KCLE. The results showed that KCLE effectively increased the glucose consumption of IR-HepG2 cells through pyruvate kinase (PK) and hexokinase (HK), promoted glycogen synthesis, and inhibited α-glucosidase and α-amylase activities. KCLE also improves diabetes by regulating AKT1, TNF, EGFR, and GSK3β. These targets (especially AKT1 and TNF) have a high binding affinity with the main active ingredients of KCLE (rutin, luteolin, demethylwedelolactone, maritimetin, and polydatin). Pathway enrichment analysis showed that the antidiabetic effect of KCLE was closely related to the PI3K-Akt signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, and FoxO signaling pathway. These findings provide a theoretical basis for promoting the pharmacodynamic development of <i>K. coccinea</i> and its application in treating diabetes.