Material basis and pharmacodynamic mechanism of Buxu Xiaoke mixture in the intervention of type 2 diabetes mellitus: Based on serum pharmacochemistry and network pharmacology.

OBJECTIVE

To investigate the material basis for the efficacy of Buxu Xiaoke Mixture (BXM) in the treatment of type 2 diabetes mellitus (T2DM).

METHODS

A rat model of T2DM was established, and the model rats were orally administered BXM. Serum samples were collected from both the control group and the administration group. The chemical constituents of BXM and the serum samples were analyzed using UHPLC-Q Exactive-Orbitrap MS technology. By integrating database searches and literature reviews, the chemical components of BXM, as well as the prototype compounds and metabolites present in the rat serum, were identified. The material basis of BXM for its anti-T2DM effects was investigated by analyzing its blood-entry components through a combination of integrated network pharmacology and molecular docking. Further, in vivo experiments demonstrated that BXM effectively ameliorates T2DM-related parameters.

RESULTS

A total of 81 compounds were identified from BXM. Among these, 25 prototype compounds and 14 metabolites derived from BXM were detected in the rat serum.Core targets (HSP90AA1, PIK3R1, SRC), mechanistically linked to insulin resistance, lipid metabolism, and inflammation, were identified. The strong binding of BXM components to these targets, coupled with in vivo evidence of improved glycemic, lipid, and inflammatory indicators, corroborates the multi-target action of BXM and demonstrates its effectiveness in controlling T2DM progression.

CONCLUSION

These components may represent the potential material basis for the efficacy of BXM in the treatment of T2DM.