An herbal formula alleviates hyperuricemia: Evidence from network pharmacology and in vivo experiments

Qianhua Tongfeng Capsule (QHTFC), an herbal formula, has demonstrated favorable therapeutic efficacy in the clinical management of hyperuricemia (HUA) and gout. Phytochemical analysis revealed that QHTFC is primarily composed of coumarins, flavonoids, and alkaloids. Nevertheless, the anti-hyperuricemic mechanisms of QHTFC remain to be further elucidated. This study aimed to elucidate the molecular targets and potential mechanisms of QHTFC in the treatment of hyperuricemia (HUA) by combining network pharmacology with in vivo experimental validation. Network pharmacology was employed to predict the potential targets and signaling pathways of QHTFC against HUA. Subsequently, in vivo experiments were conducted to evaluate the effects of QHTFC on serum biochemical markers, oxidative stress indices, and renal histopathological changes in HUA rats. Moreover, the expression levels of uric acid transporter-related proteins in the kidney were analyzed using Western blotting to further validate the underlying mechanisms. Based on network pharmacology analysis, 57 intersecting targets between QHTFC and HUA were identified. Among them, IL-6, TNF, PPARγ, CXCL8, PTGS2, and ABCG2 were determined as key targets. KEGG enrichment analysis further indicated that the primary therapeutic pathway of QHTFC against HUA involved the IL-17 signaling pathway. In vivo results revealed that QHTFC exerted potent uric acid-lowering efficacy in hyperuricemic models by bidirectional modulation of uric acid transporters. Mechanistically, QHTFC suppressed liver XOD activity, thereby reducing uric acid production. Additionally, it promoted uric acid excretion both by upregulating OAT1 and ABCG2 transporters and suppressing reabsorption through the downregulation of GLUT9 and URAT1 expression. Our findings suggest that QHTFC can significantly reduce serum UA levels and ameliorate renal injury by regulating oxidative stress, inflammation, and kidney fibrosis. This research provides new evidence supporting the application of QHTFC in the treatment of hyperuricemia.