Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Int Immunopharmacol. 2019 Oct;75:105813. doi: 10.1016/j.intimp.2019.105813. Epub 2019 Aug 9.
Our previous studies demonstrated that oral administration of madecassoside could markedly attenuate collagen-induced arthritis in rats, a rodent model of rheumatoid arthritis. As the autonomic nervous system is critically involved in the modulation of peripheral inflammation and immune response, the present study aims to explore the possible involvement of adrenergic and cholinergic nerves in the effect of madecassoside on rheumatoid arthritis. Arthritis was induced by chicken collagen in rats, and madecassoside was orally administered daily for two weeks from day 14 after the primary immunization. The antagonists of adrenoceptor and cholinergic receptors were co-administered with madecassoside, respectively. Unilateral cervical vagotomy was performed four days before the arthritis induction. The results showed that madecassoside (30 mg/kg) treatment markedly ameliorated arthritis symptoms in rats, mainly evidenced by the reduction of paw swelling and arthritis index scores. Co-administration of madecassoside with atropine (an antagonist of the muscarinic acetylcholine receptor) or hexamethonium (an antagonist of the nicotinic acetylcholine receptor) markedly diminished the therapeutic effects of madecassoside in arthritis. However, co-administration with phentolamine (an antagonist of the α-adrenoceptor) or propranolol (an antagonist of the β-adrenoceptor) did not alter the effect of madecassoside on arthritis. Furthermore, unilateral cervical vagotomy significantly reduced the anti-arthritis efficacy of madecassoside, including the amelioration of clinical symptoms, as well as the inhibition of the production of pro-inflammatory cytokines except T lymphocytes-related cytokines. These findings suggest that madecassoside exerts inhibitory effects on collagen-induced arthritis through, at least partially, the peripheral cholinergic system.
我们之前的研究表明，口服玛咖酰胺可显著减轻胶原诱导性关节炎大鼠（类风湿关节炎的啮齿动物模型）的关节炎症状。由于自主神经系统在调节外周炎症和免疫反应中起着至关重要的作用，本研究旨在探讨肾上腺素能和胆碱能神经在玛咖酰胺对类风湿关节炎作用中的可能参与。采用鸡胶原蛋白诱导关节炎，于初次免疫后第 14 天开始每日口服给予玛咖酰胺 2 周。分别给予肾上腺素能受体和胆碱能受体拮抗剂与玛咖酰胺共同给药。关节炎诱导前 4 天进行单侧颈迷走神经切断术。结果表明，玛咖酰胺（30mg/kg）治疗可显著改善大鼠关节炎症状，主要表现为爪肿胀和关节炎指数评分降低。玛咖酰胺与阿托品（毒蕈碱型乙酰胆碱受体拮抗剂）或六烃季铵（烟碱型乙酰胆碱受体拮抗剂）共同给药可显著减弱玛咖酰胺的治疗作用。然而，与酚妥拉明（α-肾上腺素能受体拮抗剂）或普萘洛尔（β-肾上腺素能受体拮抗剂）共同给药并不改变玛咖酰胺对关节炎的作用。此外，单侧颈迷走神经切断术显著降低了玛咖酰胺的抗关节炎疗效，包括临床症状的改善以及除 T 淋巴细胞相关细胞因子以外的促炎细胞因子的产生抑制。这些发现表明，玛咖酰胺通过外周胆碱能系统至少部分地对胶原诱导性关节炎发挥抑制作用。
