Bioactive Evaluation of Naringenin in Ameliorating Hyperuricemia-Induced Liver Injury by Inhibiting Xanthine Oxidase

Abstract

Hyperuricemia (HUA) is one of main risk factors for liver injury, and xanthine oxidase (XOD) is an important target for HUA-induced liver injury. As a typical natural active ingredient, naringenin (NAR) has been confirmed the good therapeutic effect on variety of diseases. However, studies of NAR ameliorating HUA-induced liver injury have not been reported. Therefore, we evaluated the bioactivity of NAR in ameliorating HUA-induced liver injury and investigated the related molecular mechanisms. The inhibitory activity and type of NAR on XOD was investigated by enzymatic reactions and kinetic analyses, and molecular docking showed that NAR was able to bind tightly to XOD. In vivo activity studies showed that NAR ameliorated liver function while being able to inhibit XOD activity. NAR alleviated oxidative stress in the liver caused by excess reactive oxygen species through antioxidant activity. At the same time, NAR exerted anti-inflammatory activity by regulating the levels of inflammatory factors. The molecular docking results suggested that NAR was able to interact with Keap1 and AMPK to exhibit antioxidant and anti-inflammatory effects. This work demonstrated the therapeutic effect of NAR on HUA-induced liver injury, which was valuable for the further development of related functional foods.