Kaempferol attenuates gouty arthritis by regulating the balance of Th17/Treg cells and secretion of IL-17

Abstract

Abstract Background Kaempferol is a common flavonoid aglycone widely found in plants. It exhibits beneficial therapeutic effects in the treatment of arthritis. However, the effects of kaempferol on gouty arthritis (GA) have not been verified. This study aimed to explore the potential mechanisms by which kaempferol regulates GA by network pharmacology and experimental validation. Methods Potential drug targets for GA were identified with a protein–protein interaction network. Then, we performed a KEGG pathway analysis to elucidate the major pathway involved in the kaempferol-mediated treatment of GA. In addition, the molecular docking was performed. A rat model of GA was constructed to verify the results of network pharmacology analysis and investigate the mechanism of kaempferol against GA. Results The network pharmacology study indicated that there were 275 common targets of kaempferol and GA treatment. Kaempferol exerted therapeutic effects on GA, in part, by regulating the IL-17, AGE-RAGE, p53, TNF, and FoxO signalling pathways. Molecular docking results showed that kaempferol stably docked with the core MMP9, ALB, CASP3, TNF, VEGFA, CCL2, CXCL8, AKT1, JUN and INS. Experimental validation suggested that kaempferol eased MSU-induced mechanical allodynia, ankle oedema and inflammation. It significantly suppressed the expression of IL-1β, IL-6, TNF-α, and TGF-β1. Kaempferol also restored IL-6-induced Th17/Treg imbalance and affected RORγt and Foxp3 through IL-17 pathway. Conclusion The present study clarifies the mechanism of kaempferol against GA and provides evidence to support its clinical use.