Esculin通过Sirt1/NF-κB途径缓解骨关节炎的进展

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Tao Sun, Bingli Bai, Haohao Wu, Hailin Xing, Jian Li
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引用次数: 0

摘要

骨关节炎(OA)是一种与炎症过程相关的关节疾病,会导致关节破坏。从Fraxinus rhynchophylla Hance的茎皮中提取的Esculin(ESC)已被证明具有抗炎特性。在这项研究中,我们研究了ESC对经IL-1β处理的软骨细胞的影响及其分子机制。研究评估了 ESC 在 OA 进展中的重要性和潜在机制。通过CCK-8试验检测了暴露于ESC后软骨细胞的活力。然后对细胞进行定量聚合酶链反应(qPCR)、Western 印迹和酶联免疫吸附试验(ELISA),以分析细胞外基质(ECM)的降解和炎症的发生。通过西部印迹分析、免疫荧光(IF)和荧光素酶报告实验对 NF-κB 机制进行了评估。进行了分子对接,以预测与 ESC 相互作用的蛋白质。此外,还通过 siRNA 敲除实验探讨了 Sirt1 的重要性。为了评估ESC对内侧半月板不稳定(DMM)模型中OA的治疗效果,研究人员进行了显微计算机断层扫描(CT)、H&E、沙夫林O-快绿(S-O)和免疫组化分析。结果表明,ESC能有效抑制ECM降解,调节促炎因子水平,并调节暴露于IL-1β的软骨细胞的NF-κB信号传导。从机理上讲,我们发现 ESC 与 Sirt1 结合抑制了 NF-κB 机制的活性。此外,ESC治疗抑制了DMM模型中OA的进展。我们的研究结果表明,ESC通过调节Sirt1/NF-κB轴改善了OA的进展。这表明,ESC具有应用于治疗OA的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Esculin Alleviates Osteoarthritis Progression Through the Sirt1/NF-κB Pathway.

Osteoarthritis (OA), a joint disease associated with inflammatory processes, contributes to joint destruction. Esculin (ESC) extracted from the stem bark of Fraxinus rhynchophylla Hance has been shown to possess anti-inflammatory properties. In this study, we investigated the effect of ESC on chondrocytes treated with IL-1β and its molecular mechanism. The importance and potential mechanism of ESC in the progression of OA were evaluated. The viability of chondrocytes after exposure to ESC was examined through the CCK-8 assays. The cells were then subjected to quantitative polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assay (ELISA) techniques to analyze the degradation of the extracellular matrix (ECM) and occurrence of inflammation. The NF-κB mechanism was evaluated by western blot analysis, immunofluorescence (IF), and luciferase reporter assay. Molecular docking was performed to allow for predictions on proteins that interact with ESC. Moreover, the significance of Sirt1 was explored through a knockdown experiment based on siRNA. Micro-computed tomography (CT), H&E, Safranin O-Fast Green (S-O), and immunohistochemical analyses were carried out to assess the treatment efficacy of ESC on OA in destabilization of medial meniscus (DMM) models. ESC treatment effectively inhibited ECM degradation, modulated the levels of pro-inflammatory factors, and regulated the NF-κB signaling in chondrocytes exposed to IL-1β. Mechanistically, we found that ESCs bound to Sirt1 to inhibit the activity of the NF-κB mechanism. Furthermore, ESC treatment suppressed OA progression in the DMM models. Our findings reveal that ESC ameliorates OA progression via modulating the Sirt1/NF-κB axis. This demonstrates that ESC has the potential to be applied in the treatment of OA.

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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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