OBJECTIVE: To explore the preventive effect of Euphorbium total triterpenes (TTE) on Freund\'s complete adjuvant (FCA) induced arthritis in rats and its mechanism.
METHODS: TTE was extracted and isolated from Euphorbium, and its components were analyzed by HPLC. The safety of TTE was evaluated by an acute toxicity test in mice. Arthritis was induced in rats by injecting 0.2 mL FCA into the right hind paw toe, except for the control group, which was given the same volume of physiological saline. Tripterygium Glycosides (TG, 7.5 mg/kg) and TTE (32, 64 and 128 mg/kg) were administered by gavage for 30 days. Body weights, paw swelling, and arthritic scores were measured during the experiment process. After 30 days, blood and joints were harvested to determine various indicators of arthritis.
RESULTS: The contents of euphol and euphorbol in TTE were 47.03% and 18.77% respectively, and the maximal feasible dose of TTE in mice is 12 g/kg. The experimental results showed that arthritis indicators in rats deteriorated after FCA inducement compared with the control group. After treatment with TTE, the swelling degree and histopathological change of the hind paws in rats were significantly improved as well as arthritic score; the serum TNF-α, CRP, IL-1β, IL-6, IL-18 and RF levels in rats were significantly reduced; The expression of PI3K, AKT, P-AKT, Bcl-2, NF-κB, NLRP3 and Pro-caspase-1 protein in joint tissue were down-regulated, and the expression of Bax protein was up-regulated.
CONCLUSIONS: The results suggested that TTE possessed anti-arthritis effects, and its mechanism may be related to its anti-inflammatory and immunomodulatory properties, as well as regulation of PI3K/AKT/Bax and NF-κB/NLRP3 signaling pathway.
目的:探讨大黄总三萜(TTE)对弗氏完全佐剂(FCA)诱导的大鼠关节炎的预防作用及其机制。
方法:TTE的提取,并通过HPLC分析其成分。通过小鼠急性毒性试验评价TTE的安全性。大鼠右后足趾注射0.2mLFCA诱发关节炎,除了对照组,给予相同体积的生理盐水。雷公藤多甙(TG,7.5mg/kg)和TTE(32、64和128mg/kg)通过管饲法给药30天。身体重量,爪子肿胀,并在实验过程中测量关节炎评分。30天后,采集血液和关节以确定关节炎的各种指标。
结果:TTE中的丁香酚和丁香酚含量分别为47.03%和18.77%。小鼠TTE的最大可行剂量为12g/kg。实验结果表明,与对照组相比,FCA诱导后大鼠关节炎指标恶化。用TTE治疗后,大鼠后爪的肿胀程度和组织病理学改变以及关节炎评分显著改善;血清TNF-α,CRP,IL-1β,IL-6、IL-18和RF水平均显著降低;PI3K、AKT,P-AKT,Bcl-2,NF-κB,NLRP3和Pro-caspase-1蛋白在关节组织中表达下调,Bax蛋白表达上调。
结论:结果表明TTE具有抗关节炎作用,其机制可能与其抗炎和免疫调节特性有关,以及PI3K/AKT/Bax和NF-κB/NLRP3信号通路的调控。