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金雀异黄素通过抑制 ROS 介导的 NF-κB 信号通路在体外和体内减轻骨关节炎相关的软骨退化。

Casticin Attenuates Osteoarthritis-Related Cartilage Degeneration by Inhibiting the ROS-Mediated NF-κB Signaling Pathway in vitro and in vivo.

机构信息

Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.

Laboratory Department, Dongguan City Maternal and Child Health Hospital, Dongguan, China.

出版信息

Inflammation. 2020 Jun;43(3):810-820. doi: 10.1007/s10753-019-01167-y.

DOI:10.1007/s10753-019-01167-y
PMID:31897918
Abstract

Casticin, a flavonoid isolated from Vitex trifolia, has been shown to have anti-inflammatory and antitumor effects in previous studies. Osteoarthritis (OA) is a disease based on degenerative pathological changes. The disease process is often accompanied by inflammatory pathological changes. However, there is no safe and effective drug for prevention and treatment. In the present study, we aimed to clarify the role of casticin in the murine model of destabilization of the medial meniscus (DMM). Male BALB/c mice were randomly divided into three groups: Sham, DMM-induced OA treated with vehicle, and DMM-induced OA treated with casticin. Our results indicated that the casticin treatments markedly reduced the destruction of cartilage and OARSI grades compared with those of the vehicle-treated mice. The levels of matrix metalloproteinase-13 (MMP13) in cartilage were also significantly reduced in the casticin-treated mice. Casticin also significantly regulated oxidative stress and reduced inflammation in the cartilage of mice with OA. These results suggest that casticin prevents the development of posttraumatic OA in mice. Consequently, decreased reactive oxygen species levels and suppressed proinflammatory cytokine production were confirmed in casticin-treated IL-1β-stimulated ADTC5 cells. After casticin treatment, the NF-κB signaling pathway was significantly inhibited in the cells. It can be concluded that casticin can alleviate arthritis-related cartilage degeneration by inhibiting ROS-mediated NF-κB signaling pathway in vitro and in vivo.

摘要

迷迭香酸,一种从三叶芫荽中分离出来的类黄酮,在之前的研究中已被证明具有抗炎和抗肿瘤作用。骨关节炎(OA)是一种基于退行性病理变化的疾病。该疾病过程通常伴有炎症性病理变化。然而,目前还没有安全有效的预防和治疗药物。在本研究中,我们旨在阐明迷迭香酸在不稳定内侧半月板(DMM)小鼠模型中的作用。雄性 BALB/c 小鼠随机分为三组:Sham 组、DMM 诱导的 OA 模型对照组和 DMM 诱导的 OA 迷迭香酸治疗组。我们的结果表明,与模型对照组相比,迷迭香酸治疗组显著减少了软骨破坏和 OARSI 分级。迷迭香酸治疗组的软骨中基质金属蛋白酶 13(MMP13)水平也显著降低。迷迭香酸还显著调节了 OA 小鼠软骨中的氧化应激和炎症。这些结果表明,迷迭香酸可预防小鼠创伤后 OA 的发展。因此,在 IL-1β 刺激的 ADTC5 细胞中,迷迭香酸处理后细胞内的活性氧(ROS)水平降低,促炎细胞因子的产生受到抑制。迷迭香酸处理后,细胞中的 NF-κB 信号通路被显著抑制。综上所述,迷迭香酸可以通过抑制 ROS 介导的 NF-κB 信号通路来减轻体外和体内关节炎相关的软骨退化。

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