关键词: 5-LOX Arthritis Azelaic acid Freund’s complete adjuvant Molecular docking TNF-α

来  源:   DOI:10.1007/s10787-024-01512-0

Abstract:
An immunologic system attacking the body\'s own tissues is a hallmark of autoimmune disorders, which encompass a wide range of unique conditions. Numerous essential biologic functions, including the regulation of the immune system, inflammation, cell division, and tissue repair, are carried out by cytokines. Natural compounds are an effective treatment for autoimmune illnesses by modulation of inflammatory cytokines and infiltration of leukocytes into the inflamed tissue. Here, anti-arthritic study was carried out using oral administration of Azelaic acid (AzA) for 28 days with doses (20, 40, and 80 mg/kg) in Complete Freund\'s Adjuvant (CFA) induced arthritis model. AzA ameliorated the adjuvant-induced arthritis by decreasing arthritic score, paw volume, improved body-weight alterations and serum levels of PGE2, 5-LOX and anti-ccp. AzA showed significant down regulation of NF-κB, COX-II, TNF-α, IL-17, IL-1β, IL-6, and up regulation of IL4 and IL10. Hemoglobin and RBCs count remarkably increased and ESR, CRP, platelets, WBCs levels markedly reduced in post treatment. In addition, the weakened SOD (superoxide dismutase), Catalase (CAT), Glutathione (GSH) activity and the increased levels of malondialdehyde (MDA) were all reversed by AzA treatment. And showed improved radiographical and histologic alterations in the structure of the joints. Molecular docking studies targeting COX-II, iNOS, TNF-α, 5-LOX, IL4, IL10, IL-6, and IL-17 establish a correlation between theoretical and experimental results. Results showed that AzA inhibit pro-inflammatory cytokines (COX-II, TNF-α, 5-LOX, IL-17, NF-κB, IL-1β, and IL-6) and increase anti-inflammatory cytokines, which supported the anti-arthritic and immunomodulatory potential of AzA.
摘要:
免疫系统攻击身体自身组织是自身免疫性疾病的标志,其中包括广泛的独特条件。许多基本的生物功能,包括免疫系统的调节,炎症,细胞分裂,和组织修复,由细胞因子进行。天然化合物是通过调节炎性细胞因子和白细胞渗入发炎组织的自身免疫性疾病的有效治疗方法。这里,在完全弗氏佐剂(CFA)诱导的关节炎模型中,使用口服壬二酸(AzA)28天的剂量(20、40和80mg/kg)进行抗关节炎研究。AzA通过降低关节炎评分改善佐剂诱导的关节炎,爪子体积,改善体重变化和PGE2,5-LOX和抗ccp的血清水平。AzA显著下调NF-κB,COX-II,TNF-α,IL-17,IL-1β,IL-6和IL4和IL10的上调。血红蛋白和红细胞计数显着增加,ESR,CRP,血小板,WBC水平在治疗后显著降低。此外,削弱的SOD(超氧化物歧化酶),过氧化氢酶(CAT),谷胱甘肽(GSH)活性和丙二醛(MDA)水平的升高均被AzA处理逆转。并显示出关节结构的影像学和组织学改变。靶向COX-II的分子对接研究,iNOS,TNF-α,5-LOX,IL4、IL10、IL-6和IL-17建立了理论和实验结果之间的相关性。结果表明,AzA抑制促炎细胞因子(COX-II,TNF-α,5-LOX,IL-17,NF-κB,IL-1β,和IL-6)并增加抗炎细胞因子,这支持了AzA的抗关节炎和免疫调节潜力。
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