Duzhong-Gegen formula ameliorated hyperuricemia by enhancing renal uric acid excretion through activation of SIRT1.

BACKGROUND: Duzhong-Gegen formula (DGF) is prepared by decoction of Eucommia ulmoides Oliv. (Du Zhong in Chinese), Pueraria montana Merr. (Ge Gen), Zea mays l. (Yu Mi Xu) and Citrus reticulata Blanco (Chen Pi), which are all edible herbs widely used in China for thousands of years. However, whether DGF exhibits ameliorating effects on hyperuricemia (HUA) remains unclear. PURPOSE: This study was designed to investigate the effects and underlying mechanism of DGF on HUA in mice. METHODS: HUA was induced in C57BL/6 male mice by gavage of adenine/potassium oxonate for 21 days. DGF (0.7 or 1.4 g crude drug/kg/day) was orally given to HUA mice. Its beneficial effects and underlying mechanism were examined. RESULTS: Compared to HUA mice, DGF intake significantly reduced serum uric acid (UA), BUN, serum creatinine, renal morphological injury and inflammation. DGF elevated 24-h urine volume and urinary UA levels as well as the expression of UA excretion transporters ABCG2 and OAT1. Based on the components detected by UPLC/Q-TOF MS, network pharmacology combining molecular docking analysis predicted that DGF may improve HUA via activation of SIRT1 by a bioactive component cafestol. Consistent with that in vivo, cafestol enhanced UA-suppressed expression of SIRT1/NRF2/ABCG2/OAT1 in renal tubular cells HK2. Knockdown of SIRT1 blocked the recovery effects of cafestol on the expression of NRF2/ABCG2/OAT1. CONCLUSION: The results in this study suggest that DGF has an improving effect on HUA, and this effect is conducted by promoting renal UA excretion through cafestol-activated SIRT1.