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首页> 外文期刊>Drug Design, Development and Therapy >Chrysin Attenuates the NLRP3 Inflammasome Cascade to Reduce Synovitis and Pain in KOA Rats
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Chrysin Attenuates the NLRP3 Inflammasome Cascade to Reduce Synovitis and Pain in KOA Rats

机译：Chrysin衰减NLRP3炎症组级联，以减少滑膜炎和KOA大鼠的疼痛

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Purpose: Our recent reports have revealed that inhibiting NLRP3 activation reduces synovial inflammation and fibrosis in knee osteoarthritis (KOA). Synovial inflammation is involved the entire process of KOA and promotes the progression of KOA. Natural flavonoid Chrysin from Scutellariae Radix, a traditional Chinese medicine, exhibits multifarious biological activities and potentially has protective activity against osteoarthritis. However, the mechanism of Chrysin in the treatment of synovial inflammation remains elusive. The purpose of our research was to explore the anti-inflammatory effects of Chrysin on KOA, which was induced by monoiodoacetic acid (MIA) in rats by targeting the NLRP3 inflammasome in the hopes of identifying an effective drug to treat KOA. Methods: The MIA-induced KOA model was used to evaluate the cold pain threshold and paw withdrawal threshold (PWT) of joints after MIA (40 mg/mL) injection into the knee joints. Microscopically, we used LPS (5 ug/mL) and ATP (4 mmol/L) to stimulate fibroblast-like synovial cells (FLSs) to explore the underlying mechanisms and effects of Chrysin. Two staining methods, H&E and Sirius Red, were applied to assess histopathological changes in synovial membranes. Cellular signal transduction was determined by qRT-PCR and WB. Cytokine expression (inflammatory cytokines and pain-related cytokines) was detected by ELISA. The degree of chronic inflammatory pain was evaluated by c-Fos immunofluorescence. Results: The results showed that Chrysin not only attenuated synovial inflammation but also reduced the secretion of pain-related factors and increased the PWT and cold pain threshold in rats. Chrysin also inhibited NLRP3 inflammasome activation and increased IL-1β levels to alleviate the synovitis. Conclusion: Chrysin can relieve knee synovial inflammation and improve pain behavior in KOA rats, which may be related to the ability of Chrysin to inhibit NLRP3 inflammasome activation. Therefore, Chrysin may be developed as a new drug for the treatment of KOA.
机译：目的：我们最近的报道显示抑制NLRP3激活可降低膝关节骨关节炎（KOA）的滑膜炎症和纤维化。滑膜炎症涉及KOA的整个过程，促进了KOA的进展。来自Scutellariae Radix的天然类黄酮蛹，中药，表现出多种生物活性，并且可能对骨关节炎具有保护性。然而，Chrysin治疗滑膜炎症的机制仍然是难以捉摸的。我们的研究目的是探讨Chrysin对KOA的抗炎作用，通过靶向NLRP3炎性的大鼠单碘酸乙酯（MIA）诱导的抗炎作用，以鉴定有效药物治疗KOA。方法：MIA诱导的KOA模型用于评价MIA（40mg / mL）注入膝关节后关节的冷疼痛阈值和爪子退出阈值（PWT）。微观地，我们使用LPS（5ug / ml）和ATP（4mmol / L）刺激成纤维细胞状滑膜细胞（FLS）以探讨Chrysin的潜在机制和效果。两个染色方法，H＆E和Sirius Red应用于评估滑膜中的组织病理学变化。通过QRT-PCR和Wb测定细胞信号转导。 ELISA检测细胞因子表达（炎症细胞因子和疼痛相关细胞因子）。通过C-FOS免疫荧光评估慢性炎症疼痛程度。结果：结果表明，Chrysin不仅减弱了滑膜炎症，还减少了疼痛相关因素的分泌，并增加了大鼠的PWT和寒冷疼痛阈值。 Chrysin还抑制了NLRP3炎症体活化，增加了IL-1β水平以缓解滑膜炎。结论：Chrysin可以缓解膝关节滑膜炎症，改善KOA大鼠的疼痛行为，这可能与Chrysin抑制NLRP3炎性激活的能力有关。因此，蛹可以作为一种用于治疗KOA的新药。

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