Kaempferol attenuates hyperuricemia combined with gouty arthritis via urate transporters and NLRP3/NF-κB pathway modulation
Yan Huang, Cantao Li, Wenjing Xu, Fenfen Li, Ying Hua, Changyu Xu, Chenxi Wu, Yihuan Wang, Xiaoxi Zhang, Daozong Xia
Abstract
Hyperuricemia (HUA), caused by purine disorders, can lead to gouty arthritis (GA). Kaempferol (KPF), a natural flavonoid, has anti-inflammatory properties, though its mechanism in treating HUA combined with GA remains unclear. This study used a mouse model of HUA combined with GA and in vitro models with HK-2 and THP-1 cells to explore KPF's effects. Cells were treated with KPF or inhibitors of ABCG2, ROS, NLRP3 inflammasome, and nuclear factor κB (NF-κB) pathway. Quantitative assays measured uric acid (UA), creatinine, oxidative stress biomarkers, and pro-inflammatory cytokines. Histopathological analyses showed KPF improved renal and joint inflammation caused by HUA and GA. KPF alleviated oxidative stress, reduced pro-inflammatory cytokines, and regulated UA levels through the modulation of urate transporters, NLRP3 inflammasome, and NF-κB pathway. KPF's actions, partly mediated by ROS reduction, suggest it is a promising candidate for treating HUA combined with GA.