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穿心莲内酯通过抑制 MAPK 通路对类风湿关节炎有益。

Andrographolide Benefits Rheumatoid Arthritis via Inhibiting MAPK Pathways.

机构信息

Department of Rheumatology and Immunology, Linyi People's Hospital, Linyi, Shandong, 276003, China.

Department of Rheumatology and Immunology, Yidu Central Hospital, Weifang, Shandong, 262500, China.

出版信息

Inflammation. 2017 Oct;40(5):1599-1605. doi: 10.1007/s10753-017-0600-y.

Abstract

Andrographolide (AD) is the main compound distributed in medicinal herb Andrographis paniculata and exhibits anti-inflammatory activity. AD has been used for the treatment of multiple inflammatory diseases. However, the therapeutic value of AD on human rheumatoid arthritis (RA) remains unclear. In this study, we investigated the effects of AD on collagen-induced arthritis (CIA) and human RA synovial fibroblasts (RA-SFs). CIA mice were treated with AD (dissolved in 0.5% CMC-Na, 100 mg/kg per day) or vehicle (0.5% CMC-Na) daily by oral gavage for 2 weeks. The arthritis severity and joint destruction were assessed. Serum anti-collagen II antibody (anti-CII Abs) and cytokines were determined by ELISA. TNFα-stimulated human RA-SFs were treated with varying doses of AD for in vitro investigation. Results showed that AD significantly attenuated the arthritis severity and joint damage. AD treatment significantly reduced the production of serum anti-CII, TNFα, IL-1β, and IL-6. In vitro, AD decreased the secretion of IL-1β and IL-6 from TNFα-stimulated RA-SFs in a dose-dependent manner. AD treatment reduced the TNFα-induced phosphorylation of p38 MAPK and ERK1/2 in a dose-dependent manner. Thus, our findings suggest that AD confers protective effects on autoimmune arthritis through inhibiting MAPK pathways.

摘要

穿心莲内酯(AD)是分布在药用植物穿心莲中的主要化合物,具有抗炎活性。AD 已被用于治疗多种炎症性疾病。然而,AD 对人类类风湿关节炎(RA)的治疗价值尚不清楚。在这项研究中,我们研究了 AD 对胶原诱导性关节炎(CIA)和人 RA 滑膜成纤维细胞(RA-SFs)的影响。 CIA 小鼠通过口服灌胃每天用 AD(溶解在 0.5% CMC-Na 中,每天 100mg/kg)或载体(0.5% CMC-Na)处理 2 周。评估关节炎严重程度和关节破坏。通过 ELISA 测定血清抗胶原 II 抗体(抗-CII Abs)和细胞因子。用不同剂量的 AD 处理 TNFα 刺激的人 RA-SFs 进行体外研究。结果表明,AD 显著减轻关节炎严重程度和关节损伤。AD 治疗显著降低了血清抗-CII、TNFα、IL-1β 和 IL-6 的产生。在体外,AD 以剂量依赖性方式降低 TNFα 刺激的 RA-SFs 中 IL-1β 和 IL-6 的分泌。AD 治疗以剂量依赖性方式降低 TNFα 诱导的 p38 MAPK 和 ERK1/2 磷酸化。因此,我们的研究结果表明,AD 通过抑制 MAPK 途径对自身免疫性关节炎具有保护作用。

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