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丁香脂素通过调控 NF-κB 通路减轻骨关节炎。

Syringaresinol attenuates osteoarthritis via regulating the NF-κB pathway.

机构信息

Department of Orthopedic Surgery, Guizhou Provincial Orthopedics Hospital, China.

Department of Gastroenterology, The Second Hospital of Dalian Medical University, China.

出版信息

Int Immunopharmacol. 2023 May;118:109982. doi: 10.1016/j.intimp.2023.109982. Epub 2023 Mar 28.

DOI:10.1016/j.intimp.2023.109982
PMID:36989902
Abstract

Osteoarthritis (OA) is a now regarded as a worldwide whole joint disease with synovial inflammation, cartilage degeneration, and subchondral sclerosis. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used drugs for OA treatment which only relieve the symptoms and restrain the progression of OA. However, various severe adverse effects often occur in patients with long-term NSAIDs use, which heavily burdens the healthcare system and impacts the quality of life. Therefore, it is much imperative to identify alternative drugs with increased efficacy. Syringaresinol (Syr), a naturally occurring phytochemical which belonging to the lignan group of polyphenols, shows anti-tumor and anti-oxidant activities, which to benefit human health. Studies has shown Syr can regulate the inflammatory response by modulating the secretion and expression level of cytokines IL-6, IL-8, and tumor necrosis factor (TNF)-α. it also shows the inhibitory effect on NF-κB pathway in mouse cells. In the present study, we aimed to demonstrate the anti-inflammatory effects of Syr in OA. In vitro Syr treatment in IL-1β-activated mouse chondrocytes significantly restrained the expression of NO, PGE2, IL-6, TNF-α, INOS, COX-2 and MMP-13. Moreover, it considerably ameliorated the degradation of aggrecan and collagen II. Furthermore, the phosphorylation of the NF-kB signaling pathway was significantly suppressed by Syr. Moreover, in vivo, the cartilage degeneration was attenuated and the increased Osteoarthritis Research Society International (OARSI) scores were reversed in the DMM + Syr group, comprared to those in the DMM group. In sum, our study demonstrated that Syr can attenuate the inflammation in vitro and further verified its effect on OA in vivo. Thus, Syr might be a potent therapeautic alternative for OA treatment.

摘要

骨关节炎(OA)现在被认为是一种全身性关节疾病,伴有滑膜炎症、软骨退化和软骨下硬化。非甾体抗炎药(NSAIDs)是治疗 OA 的常用药物,只能缓解症状并抑制 OA 的进展。然而,长期使用 NSAIDs 的患者常出现各种严重不良反应,这给医疗保健系统带来了沉重负担,并影响了生活质量。因此,迫切需要寻找疗效更高的替代药物。丁香树脂酚(Syr)是一种天然存在的植物化学物质,属于木脂素类多酚,具有抗肿瘤和抗氧化活性,有益于人类健康。研究表明,Syr 可以通过调节细胞因子 IL-6、IL-8 和肿瘤坏死因子(TNF)-α的分泌和表达水平来调节炎症反应。它还显示出对 NF-κB 通路在小鼠细胞中的抑制作用。在本研究中,我们旨在证明 Syr 在 OA 中的抗炎作用。在体外,Syr 处理 IL-1β 激活的小鼠软骨细胞显著抑制了 NO、PGE2、IL-6、TNF-α、INOS、COX-2 和 MMP-13 的表达。此外,它显著改善了聚集蛋白聚糖和胶原 II 的降解。此外,Syr 显著抑制了 NF-κB 信号通路的磷酸化。此外,在体内,与 DMM 组相比,DMM+Syr 组的软骨退变减轻,OA 研究协会国际(OARSI)评分升高得到逆转。总之,我们的研究表明 Syr 可以在体外减轻炎症,并进一步验证了其在体内对 OA 的作用。因此,Syr 可能是治疗 OA 的一种有效替代药物。

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