Immunopathology Lab, School of Bio Sciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India.
Immunopathology Lab, School of Bio Sciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India.
Chem Biol Interact. 2015 Mar 25;230:58-70. doi: 10.1016/j.cbi.2015.02.007. Epub 2015 Feb 16.
The present study was designed to assess the combined efficacy of morin, a dietary flavanol and non-steroidal anti-inflammatory drug indomethacin against adjuvant-induced arthritis in rats, an experimental model for rheumatoid arthritis. Arthritis was induced by intradermal injection of complete freund's adjuvant (0.1 ml) into the right hind paw of the Wistar albino rats. Morin (30 mg/kg b.wt), indomethacin (3 mg/kg b.wt) and combination of morin and indomethacin were administered intraperitoneally (from 11th to 20th day) after adjuvant injection. We have found that the activities/levels of lysosomal acid hydrolases (acid phosphatase, β-galactosidase, N-acetyl glucosaminidase and cathepsin-D), glycoproteins (hexose and hexosamine), urinary constituents (hydroxyproline and glycosaminoglycans), reactive oxygen species (LPO and NO), elastase, inflammatory mediators (TNF-α, IL-1β, MCP-1, VEGF and PGE2) and paw edema were significantly increased in arthritic rats compared to controls. Whereas, the anti-oxidant status (SOD, CAT, GPx, glutathione, and ceruloplasmin), body weight and bone collagen was found to be decreased. The mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-17, IL-6 and MCP-1), inflammatory enzymes (iNOS and COX-2), RANKL, and transcription factors (NF-kB p65 and AP-1) was found upregulated in the ankle joints of arthritic rats in qRT-PCR analysis. In addition, the increased protein expression of NF-kB p65 and COX-2 was also detected by immunohistochemical analysis. On the other hand, the above said imbalances were regulated back effectively to near normal as evidenced by the histopathological and radiological analysis on combined treatment with morin and indomethacin. Our study indicates that the combination therapy was more effective than either single drug alone in suppressing the pathogenesis of RA.
本研究旨在评估膳食黄烷醇和非甾体抗炎药吲哚美辛联合应用于佐剂诱导的关节炎大鼠（类风湿关节炎的实验模型）的疗效。关节炎通过将完全弗氏佐剂（0.1 毫升）皮内注射到 Wistar 白化大鼠的右后爪中诱导。在佐剂注射后第 11 天至第 20 天，通过腹腔内给予 morin（30mg/kg b.wt）、吲哚美辛（3mg/kg b.wt）和 morin 与吲哚美辛的组合。我们发现，与对照组相比，关节炎大鼠的溶酶体酸性水解酶（酸性磷酸酶、β-半乳糖苷酶、N-乙酰氨基葡萄糖苷酶和组织蛋白酶-D）、糖蛋白（己糖和己糖胺）、尿成分（羟脯氨酸和糖胺聚糖）、活性氧（LPO 和 NO）、弹性蛋白酶、炎症介质（TNF-α、IL-1β、MCP-1、VEGF 和 PGE2）和爪肿胀的活性/水平显著升高。而抗氧化状态（SOD、CAT、GPx、谷胱甘肽和铜蓝蛋白）和体重以及骨胶原则降低。qRT-PCR 分析显示，关节炎大鼠踝关节中促炎细胞因子（TNF-α、IL-1β、IL-17、IL-6 和 MCP-1）、炎症酶（iNOS 和 COX-2）、RANKL 和转录因子（NF-kB p65 和 AP-1）的 mRNA 表达上调。此外，还通过免疫组织化学分析检测到 NF-kB p65 和 COX-2 的蛋白表达增加。另一方面，通过联合使用 morin 和吲哚美辛进行组织病理学和放射学分析，发现上述失衡得到了有效调节，接近正常水平。我们的研究表明，联合治疗比单独使用任何一种药物更能有效地抑制 RA 的发病机制。
