Amelioration effects of Cajanus cajan extracts and the active ingredient pinostrobin on hyperuricemia and related kidney injury.

Abstract

Xanthine oxidase (XO) is an effective therapeutic target for the treatment of hyperuricemia-related diseases. Cajanus cajan (L.) Millsp. (pigeon pea) is a traditional medicine and food homologous plant. Here, we found that the EtOAc extract of pigeon pea (EEP) and the active ingredient pinostrobin (PSB) showed strong XO inhibitory effects with IC₅₀ = 72.83 μg mL^-1 and 16.07 μM, respectively. Kinetic analysis showed that PSB is a reversible competitive inhibitor. Molecular docking and molecular dynamics simulations were conducted to explore the mechanisms of inhibitory activity difference against XO between PSB and its structural analogue naringenin-7,4'-dimethyl ether (NDE). Finally, we demonstrated in mice that EEP and PSB possess urate-lowering and renal protective activities, including organ coefficient assessment, transcriptome profiling, metabolomic profiling, kidney histological section evaluation, and analysis of fibrosis- and inflammation-related gene expression. Conclusively, these findings suggest that pigeon pea and PSB are promising anti-hyperuricemia agents.