Study on the active ingredients and molecular mechanisms of Polygonatum sibiricum beverage in the intervention of type 2 diabetes mellitus based on UPLC-MS, network pharmacology and experimental validation

Polygonatum sibiricum beverage (PSB), a functional beverage with hypoglycaemic effects, is based on a formula from the medical book Miao Yong Huangjing Zhi Bai Bing. However, its active ingredients and molecular mechanisms remain unclear. This study aimed to elucidate the mechanisms by which PSB exerted its therapeutic effects on type 2 diabetes mellitus (T2DM) using Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS), network pharmacology, and experimental validation. UPLC-MS identified 77 compounds in PSB, and network pharmacology predicted 318 potential T2DM-related targets. Key active ingredients, including Withanolide A, Aurantiamide acetate, and N-trans-Feruloyloctopamine, were identified. PSB treatment reduced fasting blood glucose, improved serum lipid profiles (TC, TG, HDL-C, LDL-C), and alleviated liver and pancreatic damage in T2DM mice. RT-qPCR analysis showed that PSB upregulated JUN, JAK2, MAPK3, and GSK-3β, and downregulated PI3K, AKT1. PSB regulated AGE-RAGE and PI3K-AKT pathways. These results suggested that PSB exerted therapeutic effects on T2DM through multi-component, multi-target and multi-pathway mechanisms.