Serum and urine metabolomics study revealed the amelioration of Gynura bicolor extract on high fat diet-fed and streptozotocin-induced type 2 diabetic mice based on UHPLC-MS/MS

Type 2 diabetes mellitus (T2DM) has been the most prevalent disease and has become a serious public health threat worldwide. Gynura bicolor (Willd.) DC. (GB) contains a variety of nutrients and possesses numerous activities, which might benefit those with diabetes. The current study aimed to confirm the improvement of metabolic disorders and explore the potential mechanism of GB in high fat diet-fed (HFD) and streptozotocin (STZ)-induced T2DM mice. The aboveground sample of GB was extracted with alcohol, and identified by highperformance liquid chromatography (HPLC) and liquid chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) analysis. HFD and STZ-induced T2DM mice were administrated with GB extract. Biochemical and histopathologic examinations were conducted, and metabolomics evaluation was performed in serum and urine. GB significantly reduced body weight and liver weight, reversed hyperlipidemia, hyperglycemia, insulin resistance, oxidative stress and inflammation, improved hepatic histopathological changes and lipid deposition and mitigated liver injury in T2DM mice. Serum and urine metabolomics demonstrated a variety of significantly disturbed metabolites in T2DM and these changes were reversed after GB administration, including 13S-hydroxyoctadecadienoic acid, arachidonic acid, L-Valine and so on. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the overlapping enriched pathways in the normal control group and GB group were identified, including linoleic acid metabolism, PPAR signaling pathway, protein digestion and absorption, biosynthesis of amino acids and so on. This study demonstrates that the ethanol extract of GB remarkably attenuates metabolic disorders and maintains the dynamic balance of metabolites in T2DM, providing a scientific basis for GB in the treatment of T2DM and metabolism diseases.