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灯盏花素减轻白细胞介素-1β诱导的小鼠软骨细胞炎症并预防骨关节炎进展。

Scutellarin Attenuates the IL-1β-Induced Inflammation in Mouse Chondrocytes and Prevents Osteoarthritic Progression.

作者信息

Luo Zucheng, Hu Zhichao, Bian Yujie, Su Wenting, Li Xiaoyang, Li Shi, Wu Jianbin, Shi Li, Song Yonghuan, Zheng Gang, Ni Wenfei, Xue Jixin

机构信息

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Department of Orthopaedics, Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.

出版信息

Front Pharmacol. 2020 Feb 26;11:107. doi: 10.3389/fphar.2020.00107. eCollection 2020.

Abstract

Osteoarthritis (OA) is a chronic degenerative disease wherein the articular cartilage exhibits inflammation and degradation. Scutellarin (SCU) is a flavonoid glycoside with a range of pharmacological activities, as shown in previous studies demonstrating its anti-inflammatory activity. How SCU impacts the progression of OA, however, has not been explored to date. Herein, we assessed the impact of SCU on murine chondrocytes in an OA model system. In assays, we measured chondrocyte expression of key OA-associated factors such as matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) qRT-PCR and Western blotting, the expression of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were detected by qRT-PCR. Our results showed that the downregulation of MMP-13, ADAMTS-5, COX-2, and iNOS expression by SCU and the overproduction of IL-6, TNF-α, and PGE2 induced by IL-1β were all inhibited by SCU in a concentration-dependent manner. Moreover, SCU was able to reverse aggrecan and collagen II degradation and nuclear factor-κB (NF-κB) and nuclear factor erythroid-derived 2-like 2 (Nrf2) signaling pathway activation both and . We further used a destabilization of the medial meniscus (DMM) murine model of OA to explore the therapeutic benefits of SCU . Together, our findings suggest SCU to be a potentially valuable therapeutic agent useful for treating OA.

摘要

骨关节炎(OA)是一种慢性退行性疾病,其中关节软骨会出现炎症和退化。灯盏花素(SCU)是一种具有多种药理活性的黄酮苷,如先前研究表明其具有抗炎活性。然而,迄今为止尚未探索SCU如何影响OA的进展。在此,我们在OA模型系统中评估了SCU对小鼠软骨细胞的影响。在实验中,我们通过qRT-PCR和蛋白质印迹法测量了关键OA相关因子如基质金属蛋白酶13(MMP-13)、含血小板反应蛋白基序的解聚素和金属蛋白酶5(ADAMTS-5)、环氧合酶-2(COX-2)和诱导型一氧化氮合酶(iNOS)的软骨细胞表达,并通过qRT-PCR检测白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)和前列腺素E2(PGE2)的表达。我们的结果表明,SCU对MMP-13、ADAMTS-5、COX-2和iNOS表达的下调以及IL-1β诱导的IL-6、TNF-α和PGE2的过量产生均受到SCU浓度依赖性抑制。此外,SCU能够逆转蛋白聚糖和胶原蛋白II的降解以及核因子-κB(NF-κB)和核因子红细胞衍生2样2(Nrf2)信号通路的激活。我们进一步使用内侧半月板不稳定(DMM)小鼠OA模型来探索SCU的治疗益处。总之,我们的研究结果表明SCU是一种潜在有价值的治疗剂,可用于治疗OA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b96/7054241/b6dab296a9f8/fphar-11-00107-g001.jpg

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