Anti-arthritic effects of clematichinenoside (AR-6) on PI3K/Akt signaling pathway and TNF-α associated with collagen-induced arthritis.

ABSTRACT

CONTEXT Clematichinenoside (AR-6) is a triterpene saponin from an anti-arthritic herbal formula Wei-Ling-Xian in Chinese, which is an herbal medicine derived from the dried root and rhizome of Clematis chinensis Osbeck, C. hexapetala Pall., or C. manshurica Rupr. (Ranunculaceae). OBJECTIVE: To investigate the modulating effect and explored the potential mechanism of AR-6 in rheumatoid arthritis (RA), using collagen-induced arthritis (CIA) in a rat model. MATERIALS AND METHODS: CIA was evaluated by measuring body weight, paw swelling and organ index. Expression of TNF-α, PI3K and p-Akt in synovium tissue was measured by immunohistochemistry. Furthermore, expression of TNF-α mRNA, PI3K mRNA and p-Akt mRNA was measured with RT-PCR. RESULTS: The intragastric administration of AR-6 (32, 16 and 8 mg/kg), especially the high dose level of 32 mg/kg, significantly suppressed the swelling of hind paws of CIA rats (p < 0.01) and inhibited their body weight loss (p < 0.01). Based on histopathological observation, all AR-6 groups showed great amelioration compared with model group. Moreover, AR-6 significantly reduced the production of TNF-α, PI3K and p-Akt expression by immunohistochemistry (p < 0.01), and decreased TNF-α mRNA, PI3K mRNA and p-Akt mRNA in CIA rat synovium (p < 0.01). DISCUSSION: Our study indicates the mechanism of AR-6 is associated with PI3K/Akt signaling pathway and TNF-α. CONCLUSIONS: Such characteristics relating to AR-6 curing chronic inflammation of CIA, may be effectively applied to the therapeutic potential in patients with inactive RA.