Inhibition mechanism of cordycepin and ergosterol from Cordyceps militaris Link. against xanthine oxidase and cyclooxygenase-2

Abstract

Cordyceps militaris Link. (C. militaris) is an entomopathogenic fungus that parasitizes the pupa or cocoon of lepidopteran insect larvae, with various bioactive compounds. Cordycepin and ergosterol are the two active components in C. militaris. This study aimed to evaluate the inhibitory activity of cordycepin and ergosterol against xanthine oxidase (XO) and cyclooxygenase-2 (COX-2), as well as investigate the inhibition mechanism. Cordycepin could better inhibit XO (IC₅₀ = 0.014 mg/mL) and COX-2 (IC₅₀ = 0.055 mg/mL) than ergosterol. Additionally, surface hydrophobicity and circular dichroism (CD) spectra results confirmed the conformational changes in enzymes induced by cordycepin and ergosterol. Finally, cordycepin and ergosterol significantly decreased uric acid (UA) and inflammatory factors to normal level in mice with gouty nephropathy (GN). This study could provide theoretical evidence for utilization of C. militaris in hyperuricemia-management functional foods.

Keywords: Cordycepin; Cordyceps militaris Link. (C. militaris); Cyclooxygenase-2 (COX-2); Ergosterol; Gouty nephropathy (GN); Xanthine oxidase (XO).