Kaempferol Attenuates Gouty Arthritis by Regulating the Balance of Th17/Treg Cells and Secretion of IL-17

Abstract

BackgroundKaempferol is a common avonoid aglycone widely found in plants. It exhibits bene cial therapeutic effects in the treatment of arthritis. However, the effects of kaempferol on gouty arthritis (GA) have not been veri ed. This study aimed to explore the potential mechanisms by which kaempferol regulates GA by network pharmacology and experimental validation. MethodsPotential drug targets for GA were identi ed 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. ResultsThe 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 in ammation. It signi cantly suppressed the expression of IL-1β, IL-6, TNF-α, and TGF-β1. Kaempferol also restored IL-6induced Th17/Treg imbalance and affected RORγt and Foxp3 through IL-17 pathway. ConclusionThe present study clari es the mechanism of kaempferol against GA and provides evidence to support its clinical use.

Revealing the potential bioactive components and mechanism of Qianhua Gout Capsules in the treatment of gouty arthritis through network pharmacology, molecular docking and pharmacodynamic study strategies

“…The outcomes revealed that the five main active ingredients displayed a strong binding potential to CXCL8, IL-1β, IL-6, MMP9, and PPARG. Li's experiments illustrated that kaempferol could mitigate mechanical abnormal pain, ankle edema, and inflammation in MSU by inhibiting the expression of IL-1β, IL-6, TNF-α, and TGF-β1 while restoring Th17/Treg imbalance [ 52 ]. Furthermore, kaempferol demonstrates anti-inflammatory properties by increasing the expression levels of CXCL8 and PPARG and inhibiting NF-kB activation [ 53 , 54 ].…”

“…Research has indicated a significant correlation between MMP9 and the IL-17 signaling pathway. By enhancing IL-17 signaling pathway transduction, drugs can potentially exhibit anti-inflammatory effects by upregulating the downstream target MMP9 [ 52 , 71 ]. PPARG, a nuclear hormone receptor, is found in many tissue cells and is important for controlling adipose tissue differentiation, metabolism, and protecting bones and joints.…”

A Traditional Chinese Medicine, Zhenqi Granule, Potentially Alleviates Dextran Sulfate Sodium-Induced Mouse Colitis Symptoms

“…The results of enrichment analysis showed that these targets are mainly involved in inflammation-related signaling pathways. Many of the active ingredients of Zhenqi Granule, including quercetin, kaempferol, (3R)-3-(2-hydroxy-3,4-dimethoxyphenyl)chroman-7-ol, luteolin, 7-O-methylisomucronulatol, formononetin, isorhamnetin, beta-sitosterol, hederagenin, and 3,9-di-O-methylnissolin, have been reported to have anti-inflammatory effects [ 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. The basic principle of DSS-induced acute colitis in mice is that DSS destroys the intestinal epithelium [ 60 ].…”

Exploring the pharmacological mechanism of Xianlingubao against diabetic osteoporosis based on network pharmacology and molecular docking: An observational study

“…[ 43 ] Kaempferol and Luteolin can suppress the pro-inflammatory cytokine expression, such as TNFα, IL-6, and IL-1. [ 44 , 45 ] Additionally, quercetin increases the angiogenic factor VEGFA, which drives endothelial cell proliferation, migration, and vascular tissue regeneration. Diosgenin can upregulates VEGFA and promotes angiogenesis via estrogen receptor (ER)-related PI3K/Akt and p38 mitogen-activated protein kinase (MAPK) pathways in preosteoblast-like cells.…”