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肉桂醛抗完全弗氏佐剂诱导的关节炎的新型抗关节炎机制:NF-кB/TNF-α和 IL-6/IL-23/IL-17 通路在免疫炎症反应中的作用。

Novel anti-arthritic mechanisms of trans-cinnamaldehyde against complete Freund's adjuvant-induced arthritis in mice: involvement of NF-кB/TNF-α and IL-6/IL-23/ IL-17 pathways in the immuno-inflammatory responses.

机构信息

Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.

出版信息

Inflammopharmacology. 2022 Oct;30(5):1769-1780. doi: 10.1007/s10787-022-01005-y. Epub 2022 Jun 1.

DOI:10.1007/s10787-022-01005-y
PMID:35648328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9499911/
Abstract

Trans-cinnamaldehyde (TCA), a natural cinnamaldehyde derivative of cinnamon oil, is known for anti-inflammatory, anti-bacterial, anti-fungal, anti-diabetic, and anti-cancer activities. However, no study has examined the protective mechanisms of TCA on complete Freund's adjuvant (CFA)-induced arthritis. Chronic arthritis was induced in mice by triple dose injection of 0.1 ml CFA in the first two days, then a treatment with TCA (100 mg/kg, i.p.) and the anti-arthritic drug; methotrexate (MTX, 0.75 mg/kg, i.p., 3 times/week) started from day 10 after CFA and continued till day 35.TCA ameliorated the CFA-induced arthritis features, indicated by the decrease in serum rheumatoid factor, paw swelling, arthritis index and the arthritis changes in limb histology. Additionally, TCA treatment showed anti-inflammatory actions through downregulation of TNF-α, NF-κB and COX-2 expressions and marked reduction in IL-1β, IL-6, IL-23 and IL-17 levels in inflamed paw tissues.Consequently, TCA can decrease arthritis progression and inhibit the immune/inflammatory responses initiated by TNF-α/IL-1β/IL-6/IL-23/IL-17 signals, via NF-κB modulation, almost to the same extent accomplished by MTX. Therefore, TCA could be a promising anti-arthritic drug.

摘要

反式肉桂醛(TCA)是肉桂油的一种天然肉桂醛衍生物,具有抗炎、抗菌、抗真菌、抗糖尿病和抗癌活性。然而,目前尚无研究探讨 TCA 对完全弗氏佐剂(CFA)诱导的关节炎的保护机制。通过在头两天向小鼠注射 0.1ml CFA 三次来诱导慢性关节炎,然后从 CFA 后第 10 天开始用 TCA(100mg/kg,腹腔注射)和抗关节炎药物甲氨蝶呤(MTX,0.75mg/kg,腹腔注射,每周 3 次)进行治疗,一直持续到第 35 天。TCA 减轻了 CFA 诱导的关节炎特征,表现为血清类风湿因子、爪肿胀、关节炎指数和肢体组织学关节炎变化减少。此外,TCA 治疗通过下调 TNF-α、NF-κB 和 COX-2 的表达以及显著降低炎症爪组织中 IL-1β、IL-6、IL-23 和 IL-17 水平显示出抗炎作用。因此,TCA 可以通过 NF-κB 调节,几乎与 MTX 相同的程度减少关节炎进展并抑制由 TNF-α/IL-1β/IL-6/IL-23/IL-17 信号引发的免疫/炎症反应,因此 TCA 可能是一种有前途的抗关节炎药物。

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