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

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.