Department of Orthopedics Trauma and Hand Surgery, Guangxi Medical University First Affiliated Hospital, Guangxi Medical University, Nanning, China.
Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, China; Department of Bone and Joint Surgery, Guangxi Medical University First Affiliated Hospital, Guangxi Medical University, Nanning, China.
Life Sci. 2020 Jan 1;240:116857. doi: 10.1016/j.lfs.2019.116857. Epub 2019 Sep 12.
Daphnetin (DAP) is a traditional Chinese drug usually used to treat cardiovascular diseases. Studies have confirmed the anti-inflammatory, antioxidant, anti-bacterial and insecticidal, anti-tumor and neuro-protective effects of DAP. However, its anti-arthritic potential remains unexplored. The aim of this study is to investigate the in vitro and in vivo chondroprotective effects of DAP.
The effect of DAP on primary rabbit chondrocytes was examined using recombinant human IL-1β for 24 h. For the in vivo studies, rabbits were randomly divided into groups: a normal control group and osteoarthritis (OA) groups. The OA groups received three different doses of DAP for 4 or 8 weeks. The anti-arthritic effect of DAP was assessed using histopathological examinations, qRT-PCR, western blotting and immunohistochemical analysis.
Both in vitro and in vivo results indicate that DAP exerts a protective effect against IL-1β in chondrocytes. In vitro, DAP inhibits the expression of IL-6, IL-12, MMP-3, MMP-9 and MMP-13, induced by IL-1β in rabbit chondrocytes, and stimulates the production of IL-10. The inhibitory effect of DAP on the MMPs is partially regulated by the inhibition of the PI3K/AKT, MAPK and NF-κB signaling pathways. The effect of DAP on OA may be attributed to the suppression of inflammatory factor secretion, chondrocyte apoptosis observed by the decrease in pro-apoptotic Caspase-3 and BAX, and the activation of anti-apoptotic BCL-2.
DAP has a broad range of prospects in the treatment of OA, which provides a novel therapeutic strategy for OA.
瑞香素（DAP）是一种传统的中药，常用于治疗心血管疾病。研究证实，DAP 具有抗炎、抗氧化、抗菌和杀虫、抗肿瘤和神经保护作用。然而，其抗关节炎的潜力尚未得到探索。本研究旨在探讨 DAP 的体外和体内软骨保护作用。
采用重组人白细胞介素-1β（rhIL-1β）刺激 24 h 检测 DAP 对原代兔软骨细胞的作用。在体内研究中，将兔子随机分为正常对照组和骨关节炎（OA）组。OA 组分别接受三种不同剂量的 DAP 治疗 4 或 8 周。采用组织病理学检查、qRT-PCR、Western blot 和免疫组织化学分析评估 DAP 的抗关节炎作用。
体内外结果均表明 DAP 对软骨细胞中 IL-1β具有保护作用。在体外，DAP 抑制了兔软骨细胞中由 IL-1β诱导的 IL-6、IL-12、MMP-3、MMP-9 和 MMP-13 的表达，并刺激了 IL-10 的产生。DAP 对 MMPs 的抑制作用部分是通过抑制 PI3K/AKT、MAPK 和 NF-κB 信号通路来调节的。DAP 对 OA 的作用可能归因于抑制炎症因子的分泌，观察到促凋亡 Caspase-3 和 BAX 的减少以及抗凋亡 BCL-2 的激活，从而抑制软骨细胞凋亡。
DAP 在 OA 的治疗中有广泛的应用前景，为 OA 提供了一种新的治疗策略。
