Liao Taiyang, Ding Liang, Wu Peng, Zhang Li, Li Xiaochen, Xu Bo, Zhang Haosheng, Ma Zhenyuan, Xiao Yancheng, Wang Peimin
Department of Orthopedics, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, People's Republic of China.
Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu 210029, People's Republic of China.
Drug Des Devel Ther. 2020 Jul 28;14:3015-3027. doi: 10.2147/DDDT.S261216. eCollection 2020.
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.
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.
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.
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.
我们最近的报告显示，抑制NLRP3激活可减轻膝关节骨关节炎（KOA）中的滑膜炎症和纤维化。滑膜炎症参与KOA的整个过程，并促进KOA的进展。天然黄酮白杨素来自中药黄芩，具有多种生物活性，可能对骨关节炎具有保护作用。然而，白杨素治疗滑膜炎症的机制仍不清楚。我们研究的目的是探讨白杨素对大鼠单碘乙酸（MIA）诱导的KOA的抗炎作用，通过靶向NLRP3炎性小体，以期找到一种治疗KOA的有效药物。
采用MIA诱导的KOA模型，评估向膝关节注射MIA（40mg/mL）后关节的冷痛阈值和爪退缩阈值（PWT）。在显微镜下，我们用脂多糖（LPS，5μg/mL）和三磷酸腺苷（ATP，4mmol/L）刺激成纤维样滑膜细胞（FLS），以探究白杨素的潜在机制和作用。应用苏木精-伊红（H&E）和天狼星红两种染色方法评估滑膜的组织病理学变化。通过定量逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法（WB）测定细胞信号转导。通过酶联免疫吸附测定（ELISA）检测细胞因子表达（炎性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性疼痛的程度。
结果表明，白杨素不仅减轻了滑膜炎症，还减少了疼痛相关因子的分泌，并提高了大鼠的PWT和冷痛阈值。白杨素还抑制NLRP3炎性小体的激活，并提高白细胞介素-1β水平以减轻滑膜炎。
白杨素可减轻KOA大鼠的膝关节滑膜炎症并改善疼痛行为，这可能与白杨素抑制NLRP3炎性小体激活的能力有关。因此，白杨素可能被开发成为一种治疗KOA的新药。
