Mechanistic Exploration of the Uric Acid-Lowering Effects of Clerodendranthus Spicatus Based on Animal Experiments and Proteomics
Objective:To investigate the mechanism by which Clerodendranthus Spicatus lowers uric acid(UA)levels using proteomics and animal experiments.Methods:Forty healthy SPF rats were randomly divided into five groups:Normal group,Model group,Positive drug Benzbromarone group,and High-and Low-dose Clerodendranthus Spicatus groups.The Normal group received distilled water,while the other groups were administered 10%fructose water to establish a hyperuricemia(HUA)model.Simultaneously,the Positive drug group received Benzbromarone(10 mg/kg·d),and the Clerodendranthus Spicatus High-and Low-dose groups received Clerodendranthus Spicatus(10.5 g/kg·d)for 4 weeks.Serum UA,blood urea nitrogen(BUN),and creatinine(CRE)levels were measured at 1,2,3,and 4 weeks.Kidney morphology was observed using hematoxylin-eosin(HE)staining.Real-time quantitative PCR(RT-PCR)was employed to assess the expression of ATP-binding cassette sub-family G member 2(ABCG2),glucose transporter 9(GLUT9),and urate transporter 1(URAT1)genes in the kidneys.Proteomics was used to identify differential proteins in the kidneys.Results:Compared to the Normal group,the Model group exhibited significantly elevated serum UA levels(P<0.01).Compared to the Model group,the Positive drug and High-dose Clerodendranthus Spicatus groups had significantly reduced serum UA levels at weeks 1,2,3,and 4(P<0.01,P<0.05).The Low-dose Clerodendranthus Spicatus group showed significant reductions in serum UA at weeks 3 and 4(P<0.05),but not at other time points(P>0.05).No significant changes in serum BUN levels were observed across groups(P>0.05).Compared to the Control group,the Model group had significantly elevated serum CRE levels at weeks 3 and 4(P<0.05).Compared to the Model group,the High-dose Clerodendranthus Spicatus group had significantly reduced serum CRE levels at week 4(P<0.05),while other groups showed no significant changes(P>0.05).HE staining revealed normal kidney glomeruli and tubules in the Normal group,but the Model group showed light staining in renal tubular epithelial cells,severe tubular dilation,and disordered nuclear arrangement.The Positive drug and High-and Low-dose Clerodendranthus Spicatus groups exhibited significant improvements in kidney structure.Compared to the Normal group,the Model group had significantly increased GLUT9 and URAT1 levels and decreased ABCG2 levels(P<0.01).All doses of Clerodendranthus Spicatus significantly reduced URAT1 expression and increased ABCG2 expression(P<0.01,P<0.05),with the High-dose Clerodendranthus Spicatus group showing a significant reduction in GLUT9 expression(P<0.01).Proteomics identified 1,936 proteins with altered expression in the High-dose Clerodendranthus Spicatus and Model groups,with 1,082 proteins upregulated and 854 downregulated,involving pathways related to p53 signaling,autophagy,and mTOR signaling.Conclusion:The uric acid-lowering effects of Clerodendranthus Spicatus may be related to its ability to improve kidney function,regulate the expression of ABCG2,GLUT9,and URAT1 genes,and inhibit the p53 signaling pathway,autophagy,and mTOR signaling.
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