Sangqi tea improves glucose homeostasis in Caenorhabditis elegans through IIS and SKN-1/Nrf2-associated signaling

Abstract Sangqi tea (SQT), a 1-1 combination of Mori Folium (MF) and Astragali Radix (AR), has been used as a functional tea for metabolic health. In this study, the effects of SQT on glucose homeostasis were evaluated using a Caenorhabditis elegans model, integrating network pharmacology, bioinformatics, transcriptomics, molecular docking, and molecular dynamics to identify candidate compounds and investigate potential glucose-regulatory mechanisms. In high-glucose-fed worms, SQT significantly reduced glucose and triglyceride levels and lipid accumulation while alleviating oxidative stress. Integrated network pharmacology, transcriptomic, and genetic analyses supported the involvement of insulin/IGF-1 signaling (IIS) and SKN-1/Nrf2-associated signaling in the metabolic effects of SQT, with increased nuclear localization of DAF-16 and SKN-1 and altered expression of their downstream effector genes. The integrated strategy used in this study may also provide a useful reference for investigating other combined formulations whose individual components have been extensively studied but whose integrated effects and underlying mechanisms remain unclear.