Integrated network pharmacology and gut microbiome analysis to reveal the mechanism of Qu-Zhuo-Tong-Bi decoction against hyperuricemia and gout

Ethnopharmacological relevance: Qu-zhuo-tong-bi decoction (QZTBD) is a classic Chinese herbal medicine that has shown therapeutic efficacy in clinical practice against hyperuricemia and gout. However, the potential mechanisms of QZTBD remain poorly investigated.Aim of the study: To assess the therapeutic effects of QZTBD on hyperuricemia and gout and to reveal its mechanisms of action. Materials and methods: A Uox-KO mouse model of hyperuricemia and gout was established, and QZTBD was administered at a dosage of 18.0 g/kg/d. Throughout the experimental period, the effects of QZTBD on gout symptoms were monitored and analyzed. The integrated network pharmacology and gut microbiota analysis strategy was conducted to explore the mechanism of QZTBD in the treatment of hyperuricemia and gout. Targeted metabolomic analysis was performed to investigate the variation of amino acids and Spearman's rank correlation analysis was conducted to reveal the relationship between the discrepant bacterial genera and the altered amino acid. Flow cytometry was utilized to analysis the proportion of Th17 and Treg cells, and the production of pro-inflammatory cytokines was measured by ELISA. qRT-PCR and Western blot assay were applied to detect the expression of mRNA and protein respectively. Autodock vina 1.1.2 was used to evaluate the docking interactions.Results: QZTBD treatment showed remarkable efficacy against hyperuricemia and gout with respect to attenuation of disease activity metrics through gut microbiome recovery and intestinal immune homeostasis. The administration of QZTBD significantly elevated the abundance of Allobaculum and Candidatus sacchairmonas, corrected the aberrant amino acid patterns, repaired the impaired intestinal barrier, restored the balance of Th17/Treg cells via PI3K-AKT-mTOR pathway, and reduced the levels of inflammatory cytokines such as IL-1 & beta;, IL-6, TNF-& alpha; and IL-17. Fecal microbiota transplantation from QZTBD treated mice demonstrated convincing evidence of efficacy and mechanism of QZTBD. Conclusion: Taken together, our study explores the therapeutic mechanism of an effective herbal formula, QZTBD, for gout treatment through remodeling gut microbiome and regulating the differentiation of CD4+ T cells via PI3K-AKT-mTOR pathway.