Amelioration effects of Cajanus cajan extracts and 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. (pigeonpea) is a traditional medicine and food homologous plant. Here, we found that the EtOAc extract of pigeonpea (EEP) and active ingredient pinostrobin (PSB) showed the strong XO inhibitory with IC50 = 72.83 μg/mL 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 pigeonpea and PSB were promising anti-hyperuricemia agent.