Effects of Chinese herb ingredients with different properties on OAT4, URAT1 and serum uric acid level in acute hyperuricemia mice / 中草药

ABSTRACT

Objective To study the effects of Chinese herb ingredients with different properties on transporters (URAT1 and OAT4) involved in renal urate reabsorption and serum uric acid level in acute hyperuricemia mice. Methods The OAT4, URAT1- overexpressed monoclonal cell line (MDCK-hOAT4, HEK293-hURAT1) was constructed. The inhibition effect and the half maximal inhibitory concentration (IC50) of different ingredients to transport activity of OAT4 and URAT1 mediating 14C-uric acid were determined. The effects of protocatechuic, liquiritigenin and isoliquiritigenin on serum uric acid levels in acute hyperuricemia mice were studied by the acute hyperuricemia mice induced by potassium oxonate and xanthine. Results The results indicated that nobiletin,liquiritigenin, isoliquiritigenin, licochalcone A with bitter flavor showed strong inhibition to OAT4. The IC50 of nobiletin, liquiritigenin, isoliquiritigenin, and licochalcone A on OAT4 were 0.556 μmol/L, 18.40 μmol/L, 6.831 μmol/L, and 6.825 μmol/L, respectively. Protocatechuic acid and liquiritigenin showed strong inhibition to URAT1 with IC50 of 7.709 μmol/L and 14.54 μmol/L, respectively. Liquiritigenin can significantly reduce the level of serum uric acid of acute hyperuricemia mice, increase the excretion of uric acid, and reduce the level of serum creatinine and blood urea nitrogen. Conclusion Nobiletin, liquiritigenin, isoliquiritigenin and licochalcone A can inhibit the transport activity of OAT4, while protocatechuic acid and liquiritigenin can inhibit the transport activity of URAT1. Liquiritigenin can significantly reduce the level of serum uric acid in acute hyperuricemia mice and protect kidney, the mechanism of which may be associated with the decreasing reabsorption of uric acid by inhibiting the activity of URAT1 and OAT4.