Pharmacodynamic and Metabolomic Mechanism of Shexiang Baoxin Pill Based on db/db Mice on Treating Type 2 Diabetes Mellitus

ABSTRACT Rationale Shexiang Baoxin Pill (SBP) has been shown to assist in lowering blood glucose levels in patients with type 2 diabetes mellitus (T2DM) in clinical studies. However, the antidiabetic metabolism of SBP has not yet been fully elucidated. Methods Male db/db mice were used as an animal model of T2DM. Mice were given metformin (Met), SBP, and a combination of Met and SBP in low dosage (Met‐SBP) and high dosage (Met‐HSBP) via gavage for a duration of 8 weeks, respectively. Metabolomics analysis of serum samples was performed on ultra‐high‐performance liquid chromatography coupled with Orbitrap Exploris 120 mass spectrometry. Results The animal experiment showed that SBP effectively assists in lowering fasting blood glucose levels and significantly attenuating insulin resistance in db/db mice. A total of 30 metabolites with significant changes were identified, mainly involving lipids, amino acids, and acylcarnitines. Among these regulated metabolites, 9 metabolites were affected by Met, 10 by SBP, 27 by Met‐SBP, and 9 by Met‐HSBP. The results revealed that SBP specifically regulated the dysfunction of medium‐chain acylcarnitines in the fatty acid oxidation (FAO) pathway. Additionally, the combined use of SBP and Met may play a synergistic role in treating T2DM. Conclusions SBP has a positive effect in regulating fasting glucose and insulin sensitivity in T2DM db/db mice, possibly through the FAO metabolic pathway. SBP in combination with Met may play a positive role in the inflammatory response. The results of this study may offer a theoretical foundation for the clinical application of SBP on T2DM and provide new insights for the research of traditional Chinese medicine in treating diseases.