揭示骨关节炎的分子机制:多酚作为治疗剂的潜力。

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Phytotherapy Research Pub Date : 2025-05-01 Epub Date: 2025-03-05 DOI:10.1002/ptr.8455
Syed Nasar Rahaman, Murugesan Lishadevi, Suresh Kumar Anandasadagopan
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引用次数: 0

摘要

骨关节炎(OA)的复杂性是由遗传、环境和生活方式因素的复杂相互作用所驱动的,因此需要开发一种单一的治疗方法,这是非常具有挑战性的。长期使用非甾体抗炎药(NSAIDs)和皮质类固醇通常会导致肾脏损伤和胃溃疡等不良副作用。肥胖和衰老等主要健康威胁会造成慢性低度炎症的环境,并增加关节的机械压力,导致软骨退化。此外,绝经后妇女循环17β-雌二醇水平较低,由于免疫活性增加导致促炎细胞因子产生增加,MMP表达升高,II型胶原合成减少,从而加速关节恶化。多酚是大自然赋予的神奇分子,具有抗氧化、抗菌、抗炎、雌激素、胰岛素增敏等多种生物学特性,能有效管理和治疗OA的多因素致病因素。某些多酚可以作为植物雌激素,通过与ERα和ERβ结合来模拟天然雌激素的作用,并可以作为SERMs,防止关节软骨的退化,从而减轻骨关节炎的状况。在各种骨关节炎动物模型中,这些分子下调各种促炎细胞因子、凋亡基因和基质降解蛋白酶(MMPs)的表达,同时上调主要的ECM蛋白,如II型胶原、聚集蛋白和蛋白聚糖。本文综述了骨性关节炎发生的分子机制,并探讨了不同多酚在减轻关节炎症方面的治疗潜力,以及它们在抑制软骨细胞外基质(ECM)降解和增强关节稳态方面的保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unraveling the Molecular Mechanisms of Osteoarthritis: The Potential of Polyphenols as Therapeutic Agents.

The complex nature of osteoarthritis (OA), driven by the intricate interplay of genetic, environmental, and lifestyle factors, necessitates the development of a single treatment method, which is highly challenging. The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids often leads to adverse side effects like kidney damage and stomach ulcers. Major health threats like obesity and aging create a milieu of chronic low-grade inflammation and increased mechanical stress on the joints resulting in cartilage deterioration. Additionally, postmenopausal women with lower circulating 17β-estradiol levels experience accelerated joint deterioration due to increased immune activity resulting in the increased production of pro-inflammatory cytokines, with elevated MMP expression and decreased type II collagen synthesis. Polyphenols are nature's gifted magic molecules, which possess diverse biological properties like anti-oxidant, anti-bacterial, anti-inflammatory, estrogenic, and insulin-sensitizing effects, which can manage and treat all the multi-factorial contributing factors of OA effectively. Certain polyphenols can act as phytoestrogens and mimic the effects of natural estrogen by binding to ERα and ERβ and can act as SERMs and prevent degradation of the articular cartilage thereby alleviating osteoarthritic conditions. These molecules downregulate the expression of various pro-inflammatory cytokines, apoptotic genes, and matrix-degrading proteases (MMPs) while upregulating major ECM proteins like type II collagen, aggrecan, and proteoglycans in various osteoarthritic animal models. This review provides a comprehensive overview of the molecular mechanisms involved in OA development and also explores the therapeutic potential of different polyphenols in mitigating joint inflammation and their protective effect in inhibiting the degradation of cartilage extracellular matrix (ECM) and enhancing joint homeostasis.

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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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