Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing, China.
Pharm Biol. 2013 Jan;51(1):13-22. doi: 10.3109/13880209.2012.698287. Epub 2012 Sep 21.
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).
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.
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.
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).
Our study indicates the mechanism of AR-6 is associated with PI3K/Akt signaling pathway and TNF-α.
Such characteristics relating to AR-6 curing chronic inflammation of CIA, may be effectively applied to the therapeutic potential in patients with inactive RA.
Clematichinenoside (AR-6) 是一种来自抗关节炎中草药配方魏灵仙的三萜皂苷，该配方源自毛茛科铁线莲属植物威灵仙（Clematis chinensis Osbeck）、棉团铁线莲（C. hexapetala Pall.）或东北铁线莲（C. manshurica Rupr.）的干燥根和根茎。
通过胶原诱导关节炎（CIA）大鼠模型，研究 AR-6 对类风湿关节炎（RA）的调节作用，并探讨其潜在机制。
通过测量体重、足肿胀和器官指数来评估 CIA。通过免疫组织化学法测量滑膜组织中 TNF-α、PI3K 和 p-Akt 的表达。此外，通过 RT-PCR 测量 TNF-α mRNA、PI3K mRNA 和 p-Akt mRNA 的表达。
AR-6（32、16 和 8mg/kg）灌胃给药，特别是高剂量 32mg/kg，可显著抑制 CIA 大鼠后足肿胀（p<0.01）并抑制其体重减轻（p<0.01）。基于组织病理学观察，与模型组相比，所有 AR-6 组均有明显改善。此外，AR-6 显著降低了 TNF-α、PI3K 和 p-Akt 的表达（p<0.01），并降低了 CIA 大鼠滑膜中 TNF-α mRNA、PI3K mRNA 和 p-Akt mRNA 的表达（p<0.01）。
我们的研究表明，AR-6 的作用机制与 PI3K/Akt 信号通路和 TNF-α有关。
AR-6 治疗 CIA 慢性炎症的特点，可能有效应用于治疗活动期 RA 患者。
