Network Pharmacology-Assisted Multi-Omics Analysis of Gut Microbiota–Host Metabolic Remodeling and Hepatic HPD/GSTM3-Associated Redox Responses Following Shanqijing Treatment in STZ-Induced Diabetic Mice

Background/Objectives: Shanqijing (SQJ) is a multibotanical aqueous extract prepared from an equal-ratio blend of Astragali Radix, Dioscoreae Rhizoma, Corni Fructus, Polygonati Rhizoma, and Polygonati Odorati Rhizoma. This study investigated the pharmacological effects and systems-level response pattern of SQJ in streptozotocin-induced diabetic mice.

Methods

The study integrated chemical profiling, multi-omics analyses, and network pharmacology-assisted analysis with targeted assessment of hepatic HPD/GSTM3 expression and oxidative stress.

Results

UHPLC-Orbitrap MS/MS putatively annotated 250 constituents in SQJ. SQJ lowered fasting blood glucose, improved oral glucose tolerance and serum insulin, reduced inflammatory and hepatic injury indices, and was accompanied by qualitatively improved pancreatic, hepatic, and intestinal histological appearances in representative blinded assessments. Serum metabolomics revealed the partial normalization of aromatic amino acid metabolism, lysophospholipid remodeling, α-linolenic acid metabolism, and polyunsaturated fatty acid-derived oxylipins. SQJ also reshaped the cecal microbiota and partially restored colonic short-chain fatty acids, although the SCFA response was non-monotonic across doses. Integrated metabolite–gene mapping and network pharmacology-assisted compound–target analysis prioritized metabolic and redox-associated host response nodes. Targeted hepatic assessment showed SQJ-responsive normalization of HPD and GSTM3 expression, lower MDA, and recovery of SOD activity and GSH.