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

BACKGROUND

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.

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).

CONCLUSIONS

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.