Kaempferol suppresses inflammation in mice suffering from both hyperuricemia and gouty arthritis through inhibiting NLRP3 inflammasome and NF-κB pathway

Abstract

The co-occurrence of hyperuricemia and gouty arthritis is common in patients, yet a suitable animal model for this condition is lacking. In present study, a mice model combined hyperuricemia and gouty arthritis was established. Kaempferol, a flavonoid compound with anti-inflammatory and urate-lowering properties, was administered to mice in different dosages (25, 50, and 100 mg/kg). The levels of uric acid, creatinine, blood urea nitrogen and xanthine oxidase activity were measured, then kidney and joint ankle tissues were examined for pathological changes. The expressions of renal transporters, oxidative stress and inflammatory cytokines were detected. Furthermore, the anti-inflammatory mechanism of kaempferol was verified from NOD-like receptor protein 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-κB) pathway. The results of histological analyses showed that kaempferol ameliorated the glomerular and renal tubular lesions and ankle arthritis inflammatory infiltration caused by hyperuricemia combined with gouty arthritis. Additionally, treatment with kaempferol effectively alleviated oxidative stress and decreased the levels of pro-inflammatory cytokines. The research confirmed that kidney and joint inflammation in hyperuricemia combined with gouty arthritis mice were alleviated by kaempferol via suppressing NLRP3 inflammasome and NF-κB pathway.

Hesperitin-Copper(II) Complex Regulates the NLRP3 Pathway and Attenuates Hyperuricemia and Renal Inflammation

“…Moreover, the urate excretion pathway in hyperuricemic mice was further analyzed. The dysregulation of urate transport-associated proteins (e.g., GLUT9, URAT1, OAT1, and OAT3) leads to renal insufficiency with renal uric acid reabsorption increased and excretion decreased, which was supposed to be the reason for the development of hyperuricemia in mice [60]. Our study indicated that the Hsp-Cu(II) complex downregulated URAT1 and GLUT9 protein expression and upregulated OAT1 protein expression.…”

Flavonoids and Flavonoid-Based Nanoparticles for Osteoarthritis and Rheumatoid Arthritis Management

“…Kaempferol, recognized for its anti-inflammatory and urate-lowering properties, was administered in various dosages (25, 50, and 100 mg/kg) to assess its impact on uric acid levels, renal function, and joint pathology. Through detailed examinations of kidney and joint tissues, the study delved into kaempferol's efficacy in mitigating hyperuricemia-induced damage [101]. Histological analyses confirmed that kaempferol effectively ameliorated glomerular and renal tubular lesions as well as inflammatory infiltration in the ankle joints induced by hyperuricemia combined with gouty arthritis.…”

“…Histological analyses confirmed that kaempferol effectively ameliorated glomerular and renal tubular lesions as well as inflammatory infiltration in the ankle joints induced by hyperuricemia combined with gouty arthritis. The study further explored the mechanisms underlying kaempferol's effects, focusing on its modulation of the NOD-like receptor protein 3 (NLRP3) inflammasome and the NF-κB pathway [101] (Figures 2 and 3).…”