背景:类风湿性关节炎(RA)是一种多因素,多基因炎症性疾病。Mesuaassamica(King&Prain)Kosterm.(MA)是南亚本土的濒危药用植物,主要是印度的阿萨姆邦。据说树皮具有抗炎作用,抗糖尿病,抗癌,和抗疟疾特性;然而,其在RA中的作用尚未阐明。因此,本研究旨在研究苦参素树皮乙醇提取物(MAE)的体外和体内抗关节炎作用。
目的:本研究旨在研究MAE在体外对RAW264.7细胞的抗氧化和抗炎作用以及在体内对CFA诱导的佐剂性关节炎大鼠模型的抗风湿潜能。
方法:我们使用LPS触发的RAW264.7细胞研究了MAE在体外的可能治疗效果。同时,成年Wistar大鼠皮内注射100μlCFA诱导关节炎,他们以100和200mg/kg的剂量口服MAE长达28天。爪子体积分析,X射线照相术,抗氧化剂水平分析,基因和蛋白质表达研究,进行组织学分析以评估MAE在体内的作用。
结果:MAE通过降低ROS水平和降低亚硝酸盐显著减轻炎症,LPS在体外增强PGE2和COX-2水平。同时,MAE治疗减轻了CFA大鼠的爪和关节炎症,增加了免疫器官指数。组织病理学数据显示,MAE减轻了CFA引起的踝关节和滑膜组织病变。同样,MAE显著降低了促炎细胞因子的分泌,抑制TLR4,NF-κB的蛋白表达,COX-2和iNOS,以及改善Nrf2和HO-1的水平在体外和体内。
结论:所有结果都强调了MAE在体外和体内通过抑制TLR4/NF-κB/COX-2/iNOS和促进Nrf2/HO-1信号轴在RA中的抗风湿潜力。
BACKGROUND: Rheumatoid arthritis (RA) is a multifactorial, polygenic inflammatory disease. Mesua assamica (King & Prain) Kosterm. (MA) is an endangered medicinal plant indigenous to South Asia, primarily to Assam in India. The tree bark is claimed to possess anti-inflammatory, anti-diabetic, anti-cancer, and anti-malarial properties; nevertheless, its role in RA has not been elucidated. Hence, this study aims to investigate the in-vitro and in-vivo anti-arthritic effects of Mesua assamica bark ethanolic extract (MAE).
OBJECTIVE: This study aims to investigate the anti-rheumatic potential of MAE in-vitro on RAW 264.7 cells for its anti-oxidant and anti-inflammatory activities and in-vivo on the CFA-induced adjuvant arthritis in the rat model.
METHODS: We investigated the possible therapeutic effects of MAE in-vitro using RAW 264.7 cells triggered by LPS. Meanwhile, adult Wistar rats were injected intradermally with 100 μl of CFA to induce arthritis, and they were given MAE orally at doses of 100 and 200 mg/kg for up to 28 days. Paw volume analysis, X-ray radiography, anti-oxidant levels analysis, gene and protein expression studies, and histological analysis were carried out to assess the effects of MAE in-vivo.
RESULTS: MAE significantly mitigated the inflammation by reducing ROS levels and dropped the nitrite, PGE2, and COX-2 levels enhanced by LPS in-vitro. At the same time, MAE treatment reduced the paw and joint inflammation and increased the immune organ index in the CFA rats. Histopathology data revealed that MAE mitigated the CFA-induced lesions of the ankle joints and synovial tissues. Similarly, MAE significantly abated the secretion of pro-inflammatory cytokines, inhibited the protein expression of TLR4, NF-кB, COX-2, and iNOS, as well as improved the Nrf2 and HO-1 levels in-vitro and in-vivo.
CONCLUSIONS: All the results highlighted the anti-rheumatic potential of MAE in RA in-vitro and in-vivo by inhibiting the TLR4/NF-кB/COX-2/iNOS and promoting the Nrf2/HO-1 signaling axis.