Identification of coniferyl ferulate as the bioactive compound behind the xanthine oxidase inhibitory activity of Chuanxiong Rhizome

Abstract

Xanthine oxidase (XO) has been well-recognized as a key enzyme in the pathogenesis of hyperuricemia. In this study, Chuanxiong Rhizome, a tonic food widely consumed in China, was found to inhibit XO activity. The potential XO inhibitory ingredients were screened by UPLC-ZenoTOF system and bioactivity assays. Coniferyl ferulate (CF), a main constitute of Chuanxiong Rhizome, was identified as a potent XO inhibitor with an IC50 value (1.97 ± 0.11 μM) lower than that of allopurinol (2.49 ± 0.07 μM). Enzyme-kinetic assays showed that CF reversibly inhibited XO in an uncompetitive manner. And hydrogen bonds played crucial roles on the binding interaction according to the fluorescence titration and molecular docking. Moreover, the combination of CF with allopurinol exhibited a synergistic inhibitory effect on XO. Our results revealed for the first time the XO inhibitory effect of CF from Chuanxiong Rhizome, which shed light on its potential application for developing anti-hyperuricemia agents.

Keywords

• Coniferyl ferulate
• Xanthine oxidase inhibitor
• UPLC-ZenoTOF
• Isobologram
• Fluorescence quenching
• Molecular docking