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查尔酮(1,3-二苯基-2-丙烯-1-酮)作为一种治疗关节炎症的候选药物,通过降低啮齿动物体内的肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6和白细胞介素-17发挥作用:一项通过逆转录聚合酶链反应和酶联免疫吸附测定分析的研究

-Chalcone (1-3-diphenyl-2-propen-1-one) as a Therapeutic Candidate in Joint Inflammation via Reduction of TNF-α, IL-1β, IL-6, and IL-17 in Rodents: An Study by RT-PCR and ELISA analysis.

作者信息

Jabbar Zeeshan, Irfan Hafiz M, Ullah Aman, Mahmoud Mohamed H, Batiha Gaber E, Ahsan Haseeb, Khan Ajmal, Kashtoh Hamdy

机构信息

College of Pharmacy, University of Sargodha, 40100 Sargodha, Pakistan.

Punjab University College of Pharmacy, University of the Punjab, 54000 Lahore, Pakistan.

出版信息

ACS Omega. 2024 May 12;9(20):22123-22135. doi: 10.1021/acsomega.4c00368. eCollection 2024 May 21.

Abstract

Autoimmune disorders include vast and distinct illnesses and are characterized by an immune system-mediated attack on the body's own tissues. Because of their ability to impact any portion of the body, their clinical symptoms are incredibly varied. The variations in symptoms are normally linked with the release and activation of vasoactive, chemotactic substances and cytokines. Cytokines perform a multitude of vital biological tasks, such as immune response control, inflammation, proliferation, and tissue repair. The reversal of inflammatory cytokines and leukocyte infiltration into the inflamed tissue by natural compounds provides an effective remedy for autoimmune diseases. Here, the oral administration of -chalcone (TC) for 28 days was tested with gradually increasing doses (30, 60, and 120 mg/kg) in complete Freund's adjuvant (CFA)-provoked joint tissue stiffness in rats. Paw edema, arthritic index, joint stiffness, thermal and flexion pain, C-reactive protein, and rheumatoid factor (RF) levels were determined to check the tested drug effectiveness in a chronic inflammatory model. Molecular docking studies revealed strong binding affinity with inflammatory cytokines and mediators such as TNF-α, IL-17, COX-2, and iNOS; further, they were quantified at the mRNA level by RT-PCR and ELISA analysis. Oral administration of TC significantly ameliorated paw edema, thymus and spleen indices, joint stiffness, thermal and flexion pain, C-reactive protein, RF, mobility, and stance of the treated animals. This therapeutic effectiveness was linked with a reduction in the mRNA expression of proinflammatory cytokines such as IL-1β, IL-6, and IL-17. The findings of the reported research confirmed the effectiveness of TC in ameliorating joint stiffness and flexion pain by prominently lowering the inflammatory cytokines.

摘要

自身免疫性疾病包括众多不同的病症,其特征是免疫系统介导对身体自身组织的攻击。由于它们能够影响身体的任何部位,其临床症状极其多样。症状的变化通常与血管活性物质、趋化物质和细胞因子的释放及激活有关。细胞因子执行多种重要的生物学任务,如免疫反应控制、炎症、增殖和组织修复。天然化合物逆转炎性细胞因子和白细胞向炎症组织的浸润为自身免疫性疾病提供了一种有效的治疗方法。在此,对大鼠在完全弗氏佐剂(CFA)诱发的关节组织僵硬模型中,以逐渐增加的剂量(30、60和120毫克/千克)口服β-查耳酮(TC)28天进行了测试。测定爪肿胀、关节炎指数、关节僵硬、热痛和屈曲痛、C反应蛋白以及类风湿因子(RF)水平,以检查受试药物在慢性炎症模型中的有效性。分子对接研究表明,其与炎性细胞因子和介质如肿瘤坏死因子-α、白细胞介素-17、环氧化酶-2和诱导型一氧化氮合酶具有很强的结合亲和力;此外,通过逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)分析在mRNA水平对它们进行了定量。口服TC显著改善了受试动物的爪肿胀、胸腺和脾脏指数、关节僵硬、热痛和屈曲痛、C反应蛋白、RF、活动能力和站立姿势。这种治疗效果与促炎细胞因子如白细胞介素-1β、白细胞介素-6和白细胞介素-17的mRNA表达降低有关。所报道研究的结果证实了TC通过显著降低炎性细胞因子来改善关节僵硬和屈曲痛的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffb7/11112584/8a531af19a22/ao4c00368_0001.jpg

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