College of Pharmacy, University of Sargodha, Sargodha, 40100, Pakistan.
Department of Pharmacology, Punjab University College of Pharmacy, University of the Punjab, Lahore, 54000, Pakistan.
Inflammopharmacology. 2022 Apr;30(2):537-548. doi: 10.1007/s10787-022-00930-2. Epub 2022 Feb 25.
Rheumatoid arthritis is primarily associated with inflammation and increased level of proinflammatory cytokines which are released by immune cells, macrophages or activation of arachidonic acid metabolism. The expression of these cytokines, oxidative free radicals and the activation of COX-2 enzymes are crucial targets for chronic inflammation. On the basis of established anti-inflammatory efficacy of nerolidol, the primary study was further appraised to determine its approach against Freund's complete adjuvant (CFA) rheumatoid model. Arthritis was induced by inoculation of 0.1 mL CFA injection into the left hind footpad of rats. Anti-arthritic potential of nerolidol (at 200, 400 and 800 mg/kg doses) was assessed by measuring the paw volume, body weight, serum analysis, histopathological and radiographs of ankle joints. Expressions of cytokine's panels such as IL-10, IL-4, COX-2, NF-kB, TNF-α, IL-6, PGE-2 and IL-1β were determined by real-time qPCR. Antioxidant enzyme analyses were conducted by measuring the SOD, POD and catalase activity from serum and equated with arthritic control group. Nerolidol prevented body weight loss, stabilized biochemical and haematological homeostasis and significantly reduced the paw volume. Furthermore, X-ray and histopathological assessment of ankle joints showed an improvement in the joint structure of rats treated with nerolidol. Besides that, overexpression of gene pointers like TNF-α, IL-1β, IL-6, NF-kB, PGE-2 and COX-2 in CFA-treated control rats were also reversed with nerolidol. This anti-arthritic mechanism was further supported by the increased level of IL-10, IL-4 and serum antioxidant activity. The present findings demonstrate that nerolidol reduced adjuvant arthritis by downregulating the proinflammatory cytokines and upregulating the aforementioned anti-inflammatory cytokines and may be used as a therapeutic substance for the management of human rheumatoid arthritis.
类风湿性关节炎主要与炎症和促炎细胞因子水平升高有关，这些细胞因子由免疫细胞、巨噬细胞或花生四烯酸代谢激活释放。这些细胞因子、氧化自由基和 COX-2 酶的激活是慢性炎症的关键靶点。基于沉香醇的抗炎功效已经确立，本研究进一步评估了其针对完全弗氏佐剂（CFA）类风湿模型的作用机制。关节炎通过向大鼠左后足底注射 0.1mL CFA 注射液诱导。通过测量爪体积、体重、血清分析、踝关节组织病理学和 X 光片，评估沉香醇（200、400 和 800mg/kg 剂量）的抗关节炎潜力。通过实时 qPCR 测定细胞因子谱（如 IL-10、IL-4、COX-2、NF-kB、TNF-α、IL-6、PGE-2 和 IL-1β）的表达。通过测量血清中的 SOD、POD 和过氧化氢酶活性并与关节炎对照组进行比较，进行抗氧化酶分析。沉香醇可防止体重下降、稳定生化和血液学稳态，并显著减小爪体积。此外，对踝关节的 X 光和组织病理学评估表明，用沉香醇治疗的大鼠关节结构得到改善。此外，CFA 处理对照大鼠中 TNF-α、IL-1β、IL-6、NF-kB、PGE-2 和 COX-2 等基因指针的过表达也被沉香醇逆转。这种抗炎机制还得到了 IL-10、IL-4 和血清抗氧化活性增加的支持。本研究结果表明，沉香醇通过下调促炎细胞因子和上调上述抗炎细胞因子来减轻佐剂性关节炎，可作为治疗人类类风湿性关节炎的治疗物质。
