Objective To investigate the mechanism of Shengjiang powder plus Huanglian decoction in treating diabetes based on network pharmacology and animal experiments.

Methods The Traditional Chinese Medicine System Platform (TCMSP) and HERB databases were used to obtain the active ingredients and targets of Shengjiang powder plus Huanglian decoction. Diabetic-related targets were screened by integrating databases such as OMIM and DrugBank. The protein-protein interaction (PPI) network was constructed to obtain the intersection using software Venny 2.1.0. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Metascape platform, and molecular docking was performed on core components and key targets. 60 C57BL/6J mice were randomly divided into a normal control group, a model group, a positive control group (metformin 150 mg/kg), and low-, medium-, and high-dose groups (5, 10, 20 g/kg) of Shengjiang powder plus Huanglian decoction, with 10 mice in each group. Except for the normal control group, after 4 weeks of high-fat feeding, streptozotocin was injected intraperitoneally to establish a model. After intragastric administration, relevant indicators and protein expression of AKT1, TNF, and EGFR were detected.

Results Shengjiang powder plus Huanglian decoction contained 185 active components, 171 common targets associated with diabetes (AKT1, TNF, etc. were key targets), and the core ingredients were obacunone, berberine and ecdysterone. Enrichment analysis mainly involved signaling pathways such as AGE-RAGE and TNF. Molecular docking showed that the binding energies of core components and key targets were both less than -7 kcal/mol. The results of animal experiments showed that, compared with the model group, each dose group of Shengjiang powder plus Huanglian decoction could significantly lower blood glucose, improve the disorder of lipid metabolism in mice, downregulate the expression of inflammatory factors, reduce the pathological damage of pancreas, up-regulate the expression of AKT1 protein and down-regulate the expression of TNF and EGFR protein (P < 0.05); and some indicators in the medium and high dosage groups showed no significant difference from the positive control group (P > 0.05).

Conclusion Shengjiang powder plus Huanglian decoction regulates glucose and lipid metabolism and inflammatory response through multi-component, multi-target and multi-pathway synergistic regulation. The high-dose group showed significant hypoglycemic and anti-inflammatory effects comparable to those of metformin. It can be used as a candidate Chinese medicine compound for the treatment of diabetes.

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