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香芹酚通过调节促炎和抗炎细胞因子改善实验性自身免疫性脑脊髓炎。

Carvacrol ameliorates experimental autoimmune encephalomyelitis through modulating pro- and anti-inflammatory cytokines.

机构信息

Immunology Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran; Mashhad University of Medical Sciences, Mashhad, Iran.

Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran; Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.

出版信息

Life Sci. 2019 Feb 15;219:257-263. doi: 10.1016/j.lfs.2018.11.051. Epub 2018 Nov 23.

DOI:10.1016/j.lfs.2018.11.051
PMID:30472298
Abstract

AIM

The inflammatory process is a key step in multiple sclerosis (MS) development. Carvacrol exhibits various anti-inflammatory properties. We aimed to assess the Carvacrol effects on clinical manifestations and production of pro-inflammatory (IFN-γ, IL-6 and IL-17) and anti-inflammatory (TGF-β, IL-4, and IL-10) cytokines in experimental autoimmune encephalomyelitis (EAE) as MS animal model.

MAIN METHODS

EAE mice were treated with 5, 10 mg/kg dose of Carvacrol or vehicle, as the control EAE group, every other day until day-21 post EAE induction. On day22, the leukocyte infiltration within the CNS was estimated using hematoxylin-eosin staining. The cytokine production by splenocytes was determined after in vitro stimulating with myelin oligodendrocyte protein (MOG).

KEY FINDINGS

The EAE clinical scores in 5 and 10 mg/kg Carvacrol-treated mice were lower than untreated group (P < 0.001 and P < 0.01, respectively). The amounts of IFN-γ and IL-6 production by splenocytes of 5 and 10 mg/kg Carvacrol-administered mice were lower than control group (P < 0.001, and P < 0.01 for IFN-γ respectively; P ˂ 0.05 for IL-6). Splenocytes of 5 and 10 mg/kg Carvacrol-treated mice produced higher levels of TGF-β than untreated mice (P < 0.001). in splenocytes of 5 mg/kg Carvacrol-treated group the IL-10 production was higher while IL-17 secretion was lower than control group (both with P < 0.01).

SIGNIFICANCE

Carvacrol exhibits modulatory effects on expression of pro- and anti-inflammatory cytokines. It ameliorates EAE clinical and pathological consequences and therefore its potentials may be considered in treating MS patients.

摘要

目的

炎症过程是多发性硬化症(MS)发展的关键步骤。香芹酚具有多种抗炎特性。我们旨在评估香芹酚对实验性自身免疫性脑脊髓炎(EAE)作为 MS 动物模型中临床症状和促炎细胞因子(IFN-γ、IL-6 和 IL-17)和抗炎细胞因子(TGF-β、IL-4 和 IL-10)产生的影响。

主要方法

EAE 小鼠用 5、10mg/kg 剂量的香芹酚或载体(作为对照 EAE 组),每隔一天治疗,直至 EAE 诱导后第 21 天。在第 22 天,通过苏木精-伊红染色估计中枢神经系统内的白细胞浸润。用髓鞘少突胶质细胞蛋白(MOG)体外刺激后,测定脾细胞的细胞因子产生。

主要发现

与未治疗组相比,5mg/kg 和 10mg/kg 香芹酚治疗组的 EAE 临床评分较低(P<0.001 和 P<0.01)。5mg/kg 和 10mg/kg 香芹酚给药组脾细胞 IFN-γ和 IL-6 的产生量低于对照组(IFN-γ分别为 P<0.001 和 P<0.01;IL-6 为 P<0.05)。5mg/kg 和 10mg/kg 香芹酚处理组的脾细胞产生的 TGF-β水平高于未处理组(P<0.001)。在 5mg/kg 香芹酚治疗组的脾细胞中,IL-10 的产生增加,而 IL-17 的分泌减少(均为 P<0.01)。

意义

香芹酚对促炎和抗炎细胞因子的表达具有调节作用。它改善了 EAE 的临床和病理后果,因此可以考虑将其用于治疗 MS 患者。

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