Mechanism of Cordyceps militaris in gouty nephropathy explored using network pharmacology and molecular docking technology

Abstract

Cordyceps militaris Link. (C. militaris) with strong anti-hyperuricemia effects could be detected in mice urine and serum after oral administration as we previously proved. In this study, the mechanism and molecular effects of anti-hyperuricemia by C. militaris in gouty nephropathy (GN) mice were firstly investigated, and its key active structure was further explored. The results showed C. militaris could significantly reduce the uric acid (UA) level and related inflammatory factors. Meanwhile, C. militaris maintain the normal dynamic balance of UA by inhibiting hepatic xanthine oxidase (XO) and regulating the expression of renal transport proteins ABCG2, GLUT9 and URAT1. Then we employed network pharmacology to theoretically determine two active components in C. militaris, cordycepin and ergosterol, that act on GN. Moreover, the molecular docking and molecular dynamic simulation results showed cordycepin and ergosterol could stably bind to XO and cyclooxygenase-2 (COX-2) due to hydrogen bonding and hydrophobic interactions. This study could provide theoretical evidence for utilization of C. militaris in hyperuricemia-management functional foods.