Multiomics Integrative Analysis for Discovering the Potential Mechanism of Dioscin against Hyperuricemia Mice

Abstract

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 1 H 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.

Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat

“…Interestingly, we also found that PE(18:3/22:4) and PE(24:1/24:1) are the key biomarkers in the treatment of HUA with Plantaginis Semen this time. In another study, the metabolism of phospholipids is seriously disturbed in the HUA mice and hydrolysis of glycerophospholipids are restrained, causing the up-regulation in the concentration of glycerophospholipids like PCs and PEs and the down-regulation in lysophospholipids and free fatty acid [ 58 ]. The results of the two studies are not completely consistent, the effect of HUA on PE metabolism needs to be further studied.…”

Recent Updates of Natural and Synthetic URAT1 Inhibitors and Novel Screening Methods

“…(2) Terpenes . Dioscin (compound 10) ( Figure 3 ) was discovered to have weak inhibitory activity on XO in an earlier study [ 47 ] and also shows antihyperuricemic effects in animal models [ 48 – 50 ]. Zhang et al explored the metabolites of dioscin and identified tigogenin (compound 11) ( Figure 3 ) as a URAT1 inhibitor.…”

UPLC-G2Si-HDMS Untargeted Metabolomics for Identification of Yunnan Baiyao’s Metabolic Target in Promoting Blood Circulation and Removing Blood Stasis

“…Pyrimidine metabolic pathway: In this study, the content of Thymidine 5′-triphosphate and thymidine in model rats decreased, indicating that blood stasis syndrome caused abnormal pyrimidine metabolism. Studies reported that pyrimidine metabolism disorders could inhibit the synthesis of hypoxanthine transferase, resulting in hyperuricemia [ 52 , 53 ], accompanied by blood stasis [ 54 ].…”