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从 L. 中分离得到的γ-倒捻子素通过调节 miR-124-3p/IL-6/NF-κB 信号通路抑制炎症反应,缓解骨关节炎症状。

γ-Mangostin isolated from L. suppresses inflammation and alleviates symptoms of osteoarthritis via modulating miR-124-3p/IL-6/NF-κB signaling.

机构信息

Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, Taipei 23561, Taiwan.

School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.

出版信息

Aging (Albany NY). 2020 Apr 16;12(8):6630-6643. doi: 10.18632/aging.103003.

Abstract

Osteoarthritis (OA) a disease associated with joints and become severe with age, due to softening, inflammation and degradation of cartilage in joints. The agents that can target OA is needed, specifically without any side effects. L. (Mangosteen) a tropical fruit used to treat many skin and stomach associated ailments. γ- Mangostin (γ-MS) a key bioactive substance present in mangosteen. Here, we aimed to explore γ-MS potential in targeting the pro-inflammatory cytokine, factors and miRs in OA progression. Significantly, γ-MS suppresses the inflammatory cytokines (IL-6, TNF-α, and INF- γ) and factors (NF-κB, STAT3, and COX-2) which regulates/participate in the catabolic process of cartilage destruction. Result of Hematoxylin-eosin (H&E) staining of tissue sections of OA joints of γ-MS treated and non-treated mice confirm γ-MS improves the signs of injuries, and maintains the structural integrity of the articular cartilage (epiphyseal disk joints and bone marrow) and reduces inflammation. Mechanistically, γ-MS targets miR-98-5p and miR-124-3p which are found to suppress the expression IL-6 and NF-κB, respectively. But in OA these miRs are inhibited, especially miR-124-3p which regulates not only NF-κB but also TNF-α, IL-6 and MMP7. With a further investigation underway, γ-MS represents an important source for treating and managing OA.

摘要

骨关节炎(OA)是一种与关节有关的疾病,随着年龄的增长而变得严重,由于关节软骨的软化、炎症和降解。因此,需要有针对 OA 的药物,特别是没有任何副作用的药物。L.(山竹)是一种热带水果,用于治疗许多皮肤和胃部疾病。γ-山竹素(γ-MS)是山竹中的一种关键生物活性物质。在这里,我们旨在探索 γ-MS 靶向 OA 进展中促炎细胞因子、因子和 miRs 的潜力。值得注意的是,γ-MS 抑制了炎症细胞因子(IL-6、TNF-α和 INF-γ)和因子(NF-κB、STAT3 和 COX-2),这些因子调节/参与软骨破坏的分解代谢过程。γ-MS 处理和未处理的 OA 关节组织切片的苏木精-伊红(H&E)染色结果证实,γ-MS 可改善损伤迹象,并维持关节软骨(骺盘关节和骨髓)的结构完整性,减少炎症。从机制上讲,γ-MS 靶向 miR-98-5p 和 miR-124-3p,这两种 miR 分别被发现抑制 IL-6 和 NF-κB 的表达。但是在 OA 中,这些 miRs 受到抑制,特别是 miR-124-3p,它不仅调节 NF-κB,还调节 TNF-α、IL-6 和 MMP7。随着进一步的研究正在进行,γ-MS 代表了治疗和管理 OA 的重要来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e7/7202528/c7cd114e1c25/aging-12-103003-g001.jpg

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