| First Author | Lv Q | Year | 2023 |
| Journal | Biomed Pharmacother | Volume | 163 |
| Pages | 114818 | PubMed ID | 37182513 |
| Mgi Jnum | J:336564 | Mgi Id | MGI:7489318 |
| Doi | 10.1016/j.biopha.2023.114818 | Citation | Lv Q, et al. (2023) Integration of network pharmacology, transcriptomics and molecular docking reveals two novel hypoglycemic components in snow chrysanthemum. Biomed Pharmacother 163:114818 |
| abstractText | Our previous studies uncovered the glucose-lowering properties of snow chrysanthemum tea, however, the active ingredients and underlying mechanisms were yet to be uncovered. Flavonoids are the most active and abundant components in snow chrysanthemum tea. In this study, we treated leptin-deficient diabetic ob/ob or high-fat diet (HFD)-induced C57BL/6 J obese mice with or without total flavonoids of snow chrysanthemum (TFSC) for 14 weeks. Results indicated that TFSC ameliorated dyslipidemia and fatty liver, thereby reducing hyperlipidemia. Further mechanism experiments, including RNA-seq and experimental validation, revealed TFSC improved glycolipid metabolism primarily by activating the AMPK/Sirt1/PPARgamma pathway. Additionally, by integrating UPLC, network pharmacology, transcriptomics, and experimental validation, we identified two novel hypoglycemic compounds, sulfuretin and leptosidin, in TFSC. Treatment with 12.5 mumol/L sulfuretin obviously stimulated cellular glucose consumption, and sulfuretin (3.125, 6.25 and 12.5 mumol/L) significantly mitigated glucose uptake damage and reliably facilitated glucose consumption in insulin-resistant HepG2 cells. Remarkably, sulfuretin interacted with the ligand-binding pocket of PPARgamma via three hydrogen bond interactions with the residues LYS-367, GLN-286 and TYR-477. Furthermore, a concentration of 12.5 mumol/L sulfuretin effectively upregulated the expression of PPARgamma, exhibiting a comparable potency to a renowned PPARgamma agonist at 20 mumol/L. Taken together, our findings have identified two new hypoglycemic compounds and revealed their mechanisms, which significantly expands people's understanding of the active components in snow chrysanthemum that have hypoglycemic effects. |
