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

Abstract

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. • Polygonatum sibiricum beverage (PSB) improves blood glucose in T2DM mice. • PSB may exert therapeutic effects by modulating AGE-RAGE and PI3K-AKT pathways. • PSB's effects involve active ingredients like Withanolide A targeting T2DM pathways. • PSB improves liver and pancreas pathology in T2DM mice, indicating organ protection.