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异荭草素通过Nrf2/NF-κB信号通路抑制骨关节炎进展:一项体外研究

Isovitexin Depresses Osteoarthritis Progression via the Nrf2/NF-κB Pathway: An in vitro Study.

作者信息

Hu Xiaofen, Li Ruijie, Sun Ming, Kong Ying, Zhu Haifeng, Wang Fujiang, Wan Quanqing

机构信息

The Third Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, 310005, People's Republic of China.

Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People's Republic of China.

出版信息

J Inflamm Res. 2021 Apr 13;14:1403-1414. doi: 10.2147/JIR.S299557. eCollection 2021.

Abstract

PURPOSE

Osteoarthritis (OA) is a multifactorial joint disease and inflammatory processes contribute to joint destruction. Isovitexin (IVX) is a flavone component found in passion flower, Cannabis and, and the palm that is known for its anti-inflammatory properties.

MATERIALS AND METHODS

This study investigated in vitro the role and underlying mechanism used by IVX in its regulation of OA development. Effects of IVX on the viability of chondrocytes were measured by CCK-8 assays. The phenotypes of extracellular matrix (ECM) degeneration and inflammation were measured by qPCR, Western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and Western blot. Molecular docking was applied to predict the interacting protein of IVX, while Nrf2 was knocked down by siRNAs to confirm its role.

RESULTS

We demonstrated that IVX suppressed ECM degeneration and suppressed pro-inflammatory factors in IL-1β-treated chondrocytes. Additionally, IVX impact on NF-κB signaling in IL-1β-exposed chondrocytic cells; Mechanistically, it was also demonstrated in molecular docking and knock down studies that IVX might bind to Nrf2 to suppress NF-κB pathway.

CONCLUSION

Our data suggest that IVX halts OA disease advancement through the Nrf2/NF-κB axis, suggesting a possibility of IVX as a target for OA therapy.

摘要

目的

骨关节炎(OA)是一种多因素关节疾病,炎症过程会导致关节破坏。异荭草素(IVX)是一种黄酮类成分,存在于西番莲、大麻和棕榈中,以其抗炎特性而闻名。

材料与方法

本研究在体外研究了IVX在调节OA发展中的作用及其潜在机制。通过CCK-8测定法检测IVX对软骨细胞活力的影响。通过qPCR、蛋白质印迹法和酶联免疫吸附测定法检测细胞外基质(ECM)退变和炎症的表型;通过免疫荧光和蛋白质印迹法检测NF-κB信号通路。应用分子对接预测IVX的相互作用蛋白,同时用小干扰RNA敲低Nrf2以确认其作用。

结果

我们证明IVX抑制了IL-1β处理的软骨细胞中的ECM退变并抑制了促炎因子。此外,IVX影响IL-1β暴露的软骨细胞中的NF-κB信号传导;从机制上讲,分子对接和敲低研究还表明IVX可能与Nrf2结合以抑制NF-κB通路。

结论

我们的数据表明,IVX通过Nrf2/NF-κB轴阻止OA疾病进展,提示IVX作为OA治疗靶点的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/470b/8053716/e48c26282842/JIR-14-1403-g0008.jpg

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