Multiomics Integrative Analysis for Discovering the Potential Mechanism of Dioscin against Hyperuricemia Mice
2020
Tan, Yao | Wang, Liming | Gao, Jian | Ma, Junhong | Yu, Haiyang | Zhang, Yi | Wang, Tao | Han, Lifeng
Hyperuricemia is a well-known key risk factor for gout and can cause a variety of metabolic diseases. Several studies have shown that dioscin could improve metabolic symptoms and reduce the uric acid level in blood. However, there is no comprehensive metabolomic study on the anti-hyperuricemia effects of dioscin. A total of 29 adult male Kunming mice were divided into three groups: Normal (blank), PO (potassium oxonate-administrated, 200 mg/kg/day), and Dioscin (potassium oxonate + dioscin, potassium oxonate 200 mg/kg/day, dioscin 50 mg/kg/day). All mice were treated for 42 days via oral gavage. This paper implemented an untargeted metabolomics study based on ¹H NMR and LC-MS to discover the comprehensive mechanism of dioscin. Furthermore, a targeted lipidomics was fulfilled to further analyze the lipid metabolism disorder. Finally, the metabolic pathway mediated by dioscin was verified at the gene level by means of transcriptomics. The results show 53 different metabolites were closely related to the improvement of dioscin in PO-induced hyperuricemia, and 19 of them were lipids. These metabolites are mainly involved in the tricarboxylic acid cycle, lipid metabolism, amino acid metabolism, and pyrimidine metabolism. According to the transcriptomics study, the levels of 89 genes were significantly changed in the PO group compared to the normal control. Among them, six gene levels were restored by the treatment of dioscin. The six changed genes (tx1b, Tsku, Tmem163, Psmc3ip, Tcap, Tbx15) are mainly involved in the cell cycle and energy metabolism. These metabolites and genes might provide useful information for further study of the therapeutic mechanism of dioscin.
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