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

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.