Icariin alleviates MSU-induced rat GA models through NF-κB/NALP3 pathway.

Abstract

Icariin (ICA) has anti-inflammatory effects in some diseases, but its role in gouty arthritis (GA) is not clear. This study investigated the effects of ICA in monosodium urate (MSU)-induced GA rat models. GA rat models were induced by MSU, and co-treated with ICA of low-dose (20 mg/kg), medium-dose (40 mg/kg), and high-dose (80 mg/kg), respectively. The ankle swelling rates, haematoxylin-eosin (HE) staining changes, inflammatory factors (interleukin (IL)-1β, IL-6, tumour necrosis factor-α (TNF-α)) and prostaglandin E2 (PGE2 ) levels in synovial tissues were detected. The antioxidants levels in rat serum, and NF-κB pathway-related proteins and NALP3 inflammasome expressions in synovial tissues were also analysed. In cell experiments, chondrocytes were co-treated with different concentrations of ICA (1, 5, 10 μmol/L) on the basis of MSU. The activities and inflammatory cytokines, hydroxyproline (Hyp) and glycosaminogly (GAG) expressions in chondrocytes were measured. In rat experiments, MUS increased the ankle swelling rates, promoted inflammatory cells infiltration, and increased IL-1β, IL-6, TNF-α, PGE2 levels in synovial tissues, which were all alleviated by ICA. Moreover, ICA also suppressed nuclear translocation of NF-κB pathway-related proteins and reduced the expression of NALP3 inflammasome in rat models. As for cell experiments, ICA decreased the activity, inflammatory cytokines and GAG levels, and suppressed nuclear translocation of NF-κB pathway-related proteins of MSU-treated chondrocytes. In general, medium and high concentrations of ICA showed good effects. ICA has an inhibitory effect in MSU-induced rat GA models through NF-κB/NALP3 pathway, which may provide a direction for the treatment of GA. SIGNIFICANCE: Icariin (ICA) has anti-inflammatory effects in some diseases, but its role in gouty arthritis (GA) is not clear. This study excogitated that monosodium urate (MSU) increased the ankle swelling rates of rats, promoted inflammatory cells infiltration, and increased cytokines levels in synovial tissues, which were all alleviated by ICA. In related mechanism, we found that ICA might exert the catabatic functions through the NF-κB/NALP3 pathway. The findings of this study clarified that ICA may provide a direction for the treatment of patients with GA and illustrated the relevant underlying mechanism of its role.