| Aim:To explore the specific mechanism of Shi Wei Ru Xiang powder in the intervention of hyperuricemia,so as to provide objective basis for clinical application.Methods:(1)The chemical constituents of Shi Wei Ru Xiang powder were detected by UPLC-Q/TOF-MS.The active ingredients of Shi Wei Ru Xiang powder were screened based on OB and DL,and the relevant potential targets of action were predicted with the help of Swiss database.The differential targets of hyperuricemia were collected through Genecards and NCBI-gene databases.The Venny platform was used to obtain common targets.Cytoscape software was used to establish drugs-components-targets-disease network diagram.Relevant biological functions and signaling pathways were predicted by conductiong GO enrichment analysis and KEGG pathway analysis on common targets via Enrichr.(2)Based on the analysis results of network pharmacology,a mouse model of hyperuricemia induced by potassium oxonate was established.Allopurinol was used as the positive control.After 28 days of treatment with different doses of Shi Wei Ru Xiang powder,antihyperuricemia effects of Shi Wei Ru Xiang powder were studied from the aspects of biochemical indexes,histopathology,immunohistochemistry,proinflammatory cytokines and western blot,and the results of network pharmacology analysis were tested.(3)~1H-NMR was applied to operate metabolomics study and analyze the differential changes of urine metabolism in mice under the intervention of hyperuricemia and Shi Wei Ru Xiang powder.Results:(1)A total of 36 chemical components of Shi Wei Ru Xiang powder were obtained via UPLC-Q/TOF-MS technology,including flavonoids,phenolic acids and alkaloids.36 active ingredients of Shi Wei Ru Xiang powder were obtained through screening,involving 353 targets and 115 intersections with hyperuricemia targets.The network diagram of"Shi Wei Ru Xiang powder-components-targets-hyperuricemia"was constructed.2118 biological processes,104 cellular components and 322 molecular functions were identified by Go enrichment analysis.In addition,184 pathways were obtained by KEGG pathway enrichment analysis,mainly involving MAPK and NF-κB and NOD-like receptors signaling pathways.(2)Compared with the model group,under three different doses of Shiwei Ruxiang powder,the levels of uric acid(UA),creatinine(CRE)and blood urea nitrogen(BUN)were significantly reduced in serum,the levels of UA and CRE were increased in urine,the levels of xanthine oxidase(XOD)were significantly reduced in serum and liver,synthesis of UA was inhibited,under three different doses of Shi Wei Ru Xiang powder.Western blot showed that the expression levels of p38 MAPK,IκB-αand NF-κB proteins phosphorylation were regulated,the expression levels of NLRP3,ASC,Caspase-1 and IL-1βprotein was reduced,the expression levels of URAT1 and GLUT9proteins were reduced,the expression levels of OAT1 and OAT3 proteins were increased by Shi Wei Ru Xiang powder.(3)According to ~1H-NMR data,the difference of metabolic profiles of mouse in each administration group were determined.The results showed that the separation trend of the model group and the control group was obvious.After the treatment of Shi Wei Ru Xiang powder,the metabolic disorder of each administration group was alleviated to a certain extent.According to the differences between groups,a total of 26differential metabolites were identified,mainly involved in taurine and hypotaurine metabolism,glycine,serine and threonine metabolism,glyoxylate and dicarboxylate metabolism,pyruvate metabolism,purine metabolism and etc.Conclusion:Network pharmacology and in vivo experiments showed that Shi Wei Ru Xiang powder can prevent and treat hyperuricemia effectively by inhibiting uric acid production,promoting uric acid excretion and improving renal damage,whose treatment process has the features of multi-component,multi-target and multi-pathway.Metabolomics further corroborated the results of the network pharmacology study,indicating that Shi Wei Ru Xiang powder can reverse the metabolic disorder and renal damage caused by hyperuricemia through multiple metabolic pathways.This study has laid a foundation for clarifying the pharmacodynamic mechanism and clinical application of Shi Wei Ru Xiang powder against hyperuricemia. |
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