Screening and identification of potential hypoglycemic and hypolipidemic compounds from aqueous extract of Scutellaria baicalensis Georgi root combing affinity ultrafiltration with multiple drug targets and in silico analysis

Abstract Introduction Scutellaria baicalensis Georgi, a traditional Chinese medicine, is widely applied to treat various diseases among people, especially in East Asia. However, the specific active compounds in S. baicalensis aqueous extracts (SBAEs) responsible for the hypoglycemic and hypolipidemic properties as well as their potential mechanisms of action remain unclear. Objectives This work aimed to explore the potential hypoglycemic and hypolipidemic compounds from SBAE and their potential mechanisms of action. Methodology The in vitro inhibitory tests against lipase and α‐glucosidase, and the effects of SBAE on glucose consumption and total triglyceride content in HepG2 cells were first performed to evaluate the hypoglycemic and hypolipidemic effects. Then, affinity ultrafiltration liquid chromatography–mass spectrometry (LC–MS) screening strategy with five drug targets, including α‐glucosidase, α‐amylase, protein tyrosine phosphatase 1B (PTP1B), lipase and 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) was developed to screen out the potential active constituents from SBAE, and some representative active compounds were further validated. Results SBAE displayed noteworthy hypoglycemic and hypolipidemic properties, and 4, 10, 4, 8, and 8 potential bioactive components against α‐amylase, α‐glucosidase, PTP1B, HMGCR, and lipase were initially screened out, respectively. The interaction network was thus constructed between the potential bioactive compounds screened out and their corresponding drug targets. Among them, baicalein, wogonin, and wogonoside were revealed to possess remarkable hypoglycemic and hypolipidemic effects. Conclusion The potential hypolipidemic and hypoglycemic bioactive compounds in SBAE and their mode of action were initially explored through ligand–target interactions by combining affinity ultrafiltration LC–MS strategy with five drug targets.