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芳樟醇:通过降低白细胞介素-17、脾脏和胸腺指数来治疗慢性滑膜炎的单萜醇。

Linalool: Monoterpene alcohol effectiveness in chronic synovitis through lowering Interleukin-17, spleen and thymus indices.

机构信息

College of Pharmacy University of Sargodha, Sargodha, Pakistan.

College of Pharmacy University of Sargodha, Sargodha, Pakistan.

出版信息

Int Immunopharmacol. 2023 Aug;121:110517. doi: 10.1016/j.intimp.2023.110517. Epub 2023 Jun 20.

Abstract

Interleukin-17 has a positive role in the initial induction and late chronic phases of many inflammatory disorders like arthritis. This cytokine has a strong option for therapeutic targeting due to the fact that it was found in the inflamed joints of individual with rheumatoid arthritis (RA) and persuasive evidence from experimental arthritis models indicating its pro-inflammatory actions. IL-17 suppression lessened the asperity of arthritis. The present study aimed to assess the anti-arthritic potential of linalool in a model of chronic joint inflammation (CFA-mediated rheumatoid arthritis) in rats. Linalool markedly lowered spleen and thymus indices as opposed to arthritic control. The over-formation of IL-17, COX-2, TNF-α IL-1β, iNOS and IL-6 were markedly impaired in all linalool treated rats, but IL-10 was raised as compared to arthritic animals in Real time-PCR. There was reduction in associated parameters like paw volume, arthritic index, mobility score, and flexion pain score and a marked increase in stance score in CFA model as compared to the arthritic control group. Furthermore, there was improvement in body weight, hematological, tissue, and radiological parameters in the CFA-model. Molecular docking study exhibited strong binding interaction of linalool with IL-17, PGE-2, iNOS and COX-2, thus providing a good correlation among experimental and theoretical results. The current findings show that linalool reduces adjuvant arthritis by suppressing pro-inflammatory mediators, arthritic development, and spleen and thymus indices. Thus, linalool may be employed therapeutically to alleviate arthritis in humans.

摘要

白细胞介素-17 在许多炎症性疾病(如关节炎)的初始诱导和晚期慢性阶段都具有积极作用。由于该细胞因子在类风湿关节炎(RA)患者的发炎关节中被发现,并且来自实验性关节炎模型的令人信服的证据表明其具有促炎作用,因此它是一种具有很强治疗靶向性的细胞因子。IL-17 的抑制减轻了关节炎的严重程度。本研究旨在评估芳樟醇在慢性关节炎症(CFA 介导的类风湿关节炎)大鼠模型中的抗关节炎潜力。芳樟醇明显降低了脾脏和胸腺指数,而关节炎对照组则没有。与关节炎动物相比,所有芳樟醇治疗大鼠的 IL-17、COX-2、TNF-α、IL-1β、iNOS 和 IL-6 的过度形成明显受损,而 Real-time-PCR 中 IL-10 升高。与关节炎对照组相比,CFA 模型中的相关参数(如爪体积、关节炎指数、活动评分、弯曲疼痛评分)减少,而站立评分明显增加。此外,CFA 模型中的体重、血液学、组织和放射学参数也得到改善。分子对接研究表明,芳樟醇与 IL-17、PGE-2、iNOS 和 COX-2 具有很强的结合相互作用,从而为实验和理论结果提供了良好的相关性。目前的研究结果表明,芳樟醇通过抑制促炎介质、关节炎的发展以及脾脏和胸腺指数来减轻佐剂性关节炎。因此,芳樟醇可能被用于治疗人类关节炎。

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