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法尼醇可减轻弗氏完全佐剂诱导的关节炎大鼠模型中的炎症反应和氧化应激以及动脉粥样硬化的相关危险因素。

Farnesol alleviates inflammatory responses and oxidative stress in Freund's complete adjuvant induced arthritic rat model and associated risk factors of atherosclerosis.

作者信息

Anwar Isma, Sharif Ali, Ahmad Mushtaq, Shabbir Maryam, Akhtar Bushra

机构信息

Department of Pharmacology, Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Lahore, 54000, Pakistan.

Department of Plant Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan.

出版信息

Inflammopharmacology. 2025 May 29. doi: 10.1007/s10787-025-01787-x.

Abstract

This preclinical study aims to evaluate the antiarthritic and therapeutic efficacy of farnesol in a model of Freund's complete adjuvant (FCA)-induced arthritis. Farnesol was administered orally once daily for 15 days at doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg in 5% DMSO. Methotrexate (MTX) at 0.75 mg/kg was used as a standard treatment, both alone and in combination with 200 mg/kg farnesol. Hematological tests, paw thickness, body weight, and antioxidative status were measured to assess the protective effects of farnesol. Farnesol significantly increased the enzymatic activity of catalase (CAT) and superoxide dismutase (SOD), as well as the non-enzymatic activity of glutathione (GSH). In addition, farnesol reduced tissue lipid peroxidation and nitric oxide (NO) synthetase activity, which was evident by the reduced levels of oxidative stress markers malondialdehyde (MDA), asymmetric dimethylarginine (ADMA), and nitrite. Farnesol downregulated inflammatory markers, including dimethylarginine dimethylaminohydrolase 1 (DDAH 1), cortistatin (CST), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor (TNF-α), in a dose-dependent manner. These findings suggest that oral administration of farnesol, particularly in combination with MTX, effectively suppresses FCA-induced arthritis by ameliorating oxidative stress and inflammatory markers.

摘要

本临床前研究旨在评估法尼醇在弗氏完全佐剂(FCA)诱导的关节炎模型中的抗关节炎及治疗效果。法尼醇以50毫克/千克、100毫克/千克和200毫克/千克的剂量,溶于5%二甲基亚砜(DMSO)中,每日口服一次,持续15天。0.75毫克/千克的甲氨蝶呤(MTX)用作标准治疗药物,单独使用以及与200毫克/千克法尼醇联合使用。通过血液学检测、爪厚度、体重和抗氧化状态的测量来评估法尼醇的保护作用。法尼醇显著提高了过氧化氢酶(CAT)和超氧化物歧化酶(SOD)的酶活性,以及谷胱甘肽(GSH)的非酶活性。此外,法尼醇降低了组织脂质过氧化和一氧化氮(NO)合成酶活性,氧化应激标志物丙二醛(MDA)、不对称二甲基精氨酸(ADMA)和亚硝酸盐水平的降低证明了这一点。法尼醇以剂量依赖的方式下调炎症标志物,包括二甲基精氨酸二甲胺水解酶1(DDAH 1)、可体松(CST)、白细胞介素-6(IL-6)、IL-1β和肿瘤坏死因子(TNF-α)。这些研究结果表明,口服法尼醇,特别是与MTX联合使用时,可通过改善氧化应激和炎症标志物有效抑制FCA诱导的关节炎。

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