Cooperative Interaction of Hyaluronic Acid with Epigallocatechin-3-O-gallate and Xanthohumol in Targeting the NF-κB Signaling Pathway in a Cellular Model of Rheumatoid Arthritis.

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Francesco Longo, Alessandro Massaro, Manuela Mauro, Mario Allegra, Vincenzo Arizza, Luisa Tesoriere, Ignazio Restivo
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引用次数: 0

Abstract

Current intra-articular therapies with hyaluronic acid (HA) provide symptomatic relief in joint diseases, but have limited efficacy in counteracting oxidative stress and inflammation, key drivers of cartilage degradation in rheumatoid arthritis (RA). To address this limitation, the potential of combining HA with the phytochemicals xanthohumol (XAN) and epigallocatechin-3-O-gallate (EGCG), known for their antioxidant and anti-inflammatory properties, was evaluated in a cellular model of RA (SW982 synoviocytes stimulated with interleukin-1β, IL-1β). The Chou-Talalay method demonstrated that their combination synergistically reduced reactive oxygen species (ROS) and nitric oxide (NO) levels. The "TRIPLE" combination (HA + XAN + EGCG) showed the lowest combination index and the highest dose reduction index. Compared to individual treatments, TRIPLE significantly decreased IL-1β-induced IL-6, IL-8, TNF-α, and MMP-3 levels, while increasing the levels of the anti-inflammatory cytokine IL-10. Western blot analysis revealed a marked reduction in iNOS, COX-2, and MMP-3 protein expression following TRIPLE treatment. Moreover, the combination inhibited IL-1β-induced phosphorylation of IκB and p65, thereby preventing NF-κB activation. These findings suggest that integrating XAN and EGCG into injectable HA formulations may represent a promising strategy to improve the management of joint inflammation in RA.

透明质酸与表没食子儿茶素-3- o -没食子酸酯和黄腐酚在类风湿关节炎细胞模型中靶向NF-κB信号通路的协同作用。
目前使用透明质酸(HA)的关节内治疗可以缓解关节疾病的症状,但在对抗氧化应激和炎症方面的疗效有限,而氧化应激和炎症是类风湿性关节炎(RA)软骨降解的关键驱动因素。为了解决这一限制,在RA(白细胞介素-1β, IL-1β刺激的SW982滑膜细胞)的细胞模型中,研究人员评估了HA与植物化学物质黄腐酚(XAN)和表没食子儿茶素-3- o -没食子酸酯(EGCG)联合使用的潜力,它们具有抗氧化和抗炎特性。Chou-Talalay方法表明,它们的组合协同降低了活性氧(ROS)和一氧化氮(NO)的水平。“三重”组合(HA + XAN + EGCG)的联合指数最低,剂量减少指数最高。与单独治疗相比,TRIPLE显著降低il -1β诱导的IL-6、IL-8、TNF-α和MMP-3水平,同时增加抗炎细胞因子IL-10水平。Western blot分析显示,在三重治疗后,iNOS、COX-2和MMP-3蛋白表达显著降低。此外,联合用药可抑制il -1β诱导的i -κB和p65磷酸化,从而阻止NF-κB活化。这些发现表明,将XAN和EGCG整合到可注射的HA制剂中可能是改善类风湿关节炎关节炎症管理的一种有希望的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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