Extract of Aster glehni ameliorates potassium oxonate-induced hyperuricemia by modulating renal urate transporters and renal inflammation by suppressing TLR4/MyD88 signaling

Abstract

Recent studies suggest that Aster glehni extract (AGE) reduces hyperuricemia by preventing xanthine oxidase activity. However, its effect on renal urate transporters responsible for modulating urate excretion has not been examined. This study investigated whether AGE affects gene expressions of urate transporters using potassium oxonate (PO)-induced hyperuricemia rats. Furthermore, the underlying mechanisms of AGE were explored to ameliorate renal inflammation and injury by PO. AGE effectively restored PO-induced dysregulation of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), ATP-binding cassette transporter subfamily G member 2 (ABCG2), organic anion transporter 1 (OAT1), and organic cation transporter 1 (OCT1), resulting in increasing urate excretion. Additionally, AGE suppressed toll-like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88) signaling, phosphorylation of nuclear factor kappa B (NF-kappa B), and renal production of IFN-gamma, IL-1 beta, TNF-alpha, and IL-6. These results suggest that AGE may ameliorate PO-induced hyperuricemia by modulating renal transporters, and further renal inflammation via inhibiting the TLR4/MyD88/NF-kappa B signaling pathway.