The monoterpene oxide, Eucalyptol (1,8-Cineole), a primary component of eucalyptus oil, has been evaluated pharmacologically for anti-inflammatory and analgesic activity. Current research aimed to evaluate Eucalyptol’s anti-arthritic potential in a Complete Freund’s adjuvant induced arthritis that resembles human rheumatoid arthritis. Polyarthritis developed after 0.1 mL CFA injection into the left hind footpad in rats. Oral administration of Eucalyptol at various doses (100, 200 and 400 mg/kg) significantly reduced paw edema, body weight loss, 5-LOX, PGE2 and Anti-CCP levels. Real‐time PCR investigation showed significant downregulation of COX-2, TNF-α, NF-κB, IL-17, IL-6, IL-1β and upregulation of IL-4 and IL-10 in Eucalyptol treated groups. Hemoglobin and RBCs counts significantly increased post-treatment with Eucalyptol while ESR, CRP, WBCs and platelets count significantly decreased. Eucalyptol significantly increased Superoxide Dismutase, Catalase and Glutathione levels compared to CFA-induced arthritic control however, MDA significantly decreased post-treatment. Further, radiographic and histopathological examination of the ankle joints of rodents administered Eucalyptol revealed an improvement in the structure of the joints. Piroxicam was taken as standard. Furthermore, molecular docking findings supported the anti-arthritic efficacy of Eucalyptol exhibited high binding interaction against IL-17, TNF-α, IL-4, IL-10, iNOS NF-κB, 5-LOX, and COX-2. Eucalyptol has reduced the severity of CFA induced arthritis by promoting anti-inflammatory cytokines for example IL-4, IL-10 and by inhibiting pro-inflammatory cytokines such as 5-LOX, COX-2, IL-17, NF-κB, TNF-α, IL-6 and IL-1β. Therefore, Eucalyptol might be as a potential therapeutic agent because of its pronounced anti-oxidant and anti-arthritic activity.

Graphical Abstract

中文翻译：

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桉树脑 (1,8-桉叶素) 作为抗关节炎药物的分子见解：IL-17、IL-10、NF-κB、5-LOX 和 COX-2 的体内和计算机分析

单萜氧化物桉树醇（1,8-桉叶素）是桉树油的主要成分，已对其抗炎和镇痛活性进行了药理学评估。目前的研究旨在评估桉树脑在完全弗氏佐剂诱导的类似于人类类风湿性关节炎的关节炎中的抗关节炎潜力。向大鼠左后足垫注射 0.1 mL CFA 后出现多关节炎。口服不同剂量（100、200 和 400 mg/kg）的桉叶油素可显着降低爪水肿、体重减轻、5-LOX、PGE2 和抗 CCP 水平。实时 PCR 研究显示，桉树油治疗组中 COX-2、TNF-α、NF-κB、IL-17、IL-6、IL-1β 显着下调，而 IL-4 和 IL-10 显着上调。桉油醇治疗后血红蛋白和红细胞计数显着增加，而血沉、C反应蛋白、白细胞和血小板计数显着下降。与 CFA 诱导的关节炎控制相比，桉树油显着增加了超氧化物歧化酶、过氧化氢酶和谷胱甘肽水平，但治疗后 MDA 显着降低。此外，对施用桉树油的啮齿类动物的踝关节进行放射学和组织病理学检查，结果显示关节结构有所改善。以吡罗昔康为标准品。此外，分子对接结果支持桉树脑的抗关节炎功效，对 IL-17、TNF-α、IL-4、IL-10、iNOS NF-κB、5-LOX 和 COX-2 表现出高度的结合相互作用。桉油精通过促进抗炎细胞因子（例如 IL-4、IL-10）和抑制促炎细胞因子（例如 5-LOX、COX-2、IL-17、NF-κB、TNF）来降低 CFA 诱导的关节炎的严重程度-α、IL-6 和 IL-1β。因此，桉树脑因其显着的抗氧化和抗关节炎活性而可能成为一种潜在的治疗剂。

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