Astragaloside IV suppresses inflammatory mediator production in synoviocytes and collagen-induced arthritic rats

Abstract

The aim of the current study was to investigate the effects of Astragaloside-IV (AS-IV) on inflammatory mediators in synoviocytes and collagen-induced arthritic rats. Synoviocytes were stimulated with lipopolysaccharides (LPS) and Sprague-Dawley rats were injected with type II collagen. AS-IV was administered to the LPS-stimulated synoviocytes and collagen-induced arthritis (CIA) rats. The inflammation of LPS-stimulated synoviocytes and CIA rats was assessed using enzyme-linked immunosorbent assays and western blotting. Using Cell Counting Kit-8 analysis, it was demonstrated that AS-IV (5, 20 and 50 mg/ml) inhibited the LPS-stimulated synoviocytes proliferation in a dose-dependent manner. AS-IV significantly inhibited the LPS-stimulated inflammatory response, as indicated by the expression levels of TNF-α, IL-1β, IL-6 and IL-8. In addition, treatment with AS-IV significantly reduced the LPS-stimulated cyclooxygenase (COX)-1, COX-2, high mobility group box 1 protein (HMGB1) and intercellular adhesion molecule 1 overexpression, and intranuclear nuclear factor (NF)-κBp65 subunit accumulation and activation of c-Jun N-terminal kinase (JNK)1/2 and p38. Similar to the protective effects of AS-IV on LPS-stimulated synoviocytes, AS-IV treatment significantly reduced the expression levels of tumor necrosis factor α, interleukin (IL)-1β, IL-6 and IL-8 expression levels, and attenuated intranuclear NF-κBp65 subunit accumulation and overexpression of COX-2 and inducible nitric oxide synthase in CIA rats. In conclusion, the results of the present study demonstrated for the first time, to the best of our knowledge, that AS-IV protects synoviocytes against LPS-and collagen-induced inflammatory responses through inhibition of the HMGB1-dependent JNK1/2-and p38-activated NF-κB/COX-2 pathway.