Ethnopharmacological relevance: Type 2 diabetes mellitus (T2DM) poses significant threats to public health. In Traditional Chinese Medicine (TCM), the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma (PCC/AR) herb pair has long been used for T2DM treatment, although its specific anti-diabetic mechanisms remain unclear.
Aim of the study: This study aimed to elucidate the relationship between metabolomics of T2DM patients and the anti-diabetic effects of PCC/AR herb pair in mice through clinical metabolomics and both in vitro and in vivo experiments.
Materials and methods: In this study, a T2DM mouse model was established via high-fat feeding (HFD) and streptozotocin (STZ) injection. The effects of PCC/AR on blood glucose, lipid metabolism, and inflammatory markers were evaluated. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was performed for metabolomics analysis of T2DM patients.
Results: Serum metabolomics analysis identified significant alterations in metabolites linked to the biosynthesis of unsaturated fatty acids and purine metabolism in T2DM patients, with elevated 2-hydroxyvaleric acid (2HB) levels. In T2DM mice, PCC/AR intervention normalized FBG, GHbA1c, TC, TG, LDL-C, HDL-C, TNF-α and IL-1β levels, while improving insulin sensitivity and pancreatic β-cell function in T2DM mice. Notably, PCC/AR reduced key enzymes in gluconeogenesis and fatty acid synthesis, PEPCK and ACC1.
Conclusion: PCC/AR herb pair exerts an anti-diabetes effect in T2DM mice by regulating 2HB through ACC1 inhibition, thereby reducing FFA and TG synthesis. Additionally, PCC/AR may also exert its effects by modulating glucose and lipid metabolism and reducing inflammation. These results support further investigation into the PCC/AR herb pair as a complementary therapy for T2DM.
Keywords: 2-Hydroxyvaleric acid; Biomarker; Metabolomics; Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma herb pair; Type 2 diabetes mellitus.
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