The Pueraria lobata-Citrus reticulata decoction ameliorates hyperuricemia by modulating urate transporters and suppressing the PI3K/AKT/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria lobatae-Citrus reticulata Decoction (PLRY) is derived from a modified version of the "Jiawei Jiecheng Decoction" described in the renowned Qing Dynasty text Wai Ke Zheng Zhi Quan Shu. Traditionally, it has been used to treat symptoms such as "severe pain, diffuse joint swelling, and mild redness" associated with gout. Preclinical studies have shown that the combined use of Pueraria and Citrus possesses anti-hyperuricemic effects. However, the specific molecular mechanisms by which PLRY influences hyperuricemia have yet to be completely understood.

RESEARCH

OBJECTIVES

This investigation sought to evaluate the effectiveness of PLRY against hyperuricemia and to uncover the mechanisms driving its effects.

METHODS

The chemical constituents of PLRY were characterized by UPLC-Q-Orbitrap HRMS. Mice were randomized into normal (n = 10), model, BPC, and PLRY (1.5, 2.5, 3.5 g/kg; n = 11 each) groups. A hyperuricemic mouse model was established by oral administration of potassium oxonate and hypoxanthine for 6 weeks to evaluate the effects of PLRY. Network pharmacology was used to predict potential targets and signaling pathways. RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence were performed to explore the potential anti-hyperuricemic mechanisms of PLRY.

RESULTS

UPLC-Q-Orbitrap HRMS identified 32 major chemical constituents in PLRY. PLRY significantly reduced serum uric acid levels in hyperuricemic mice and alleviated HUA-induced renal injury (P < 0.05 or P < 0.01). PLRY downregulated the uric acid reabsorption-related transporters URAT1, GLUT9, and OAT4, while upregulating the uric acid excretion-related transporters OAT1, OAT3, and ABCG2. Network pharmacology prediction and protein validation revealed that PLRY inhibits the PI3K/AKT/NF-κB pathway to alleviate renal inflammation.

CONCLUSION

PLRY treatment ameliorates renal and intestinal dysfunction in hyperuricemic mice by promoting uric acid excretion. In addition, PLRY inhibits the PI3K/AKT/NF-κB signaling pathway, thereby alleviating renal inflammation.