Chondroprotective and antiarthritic effects of daphnetin used in vitro and in vivo osteoarthritis models.
Chondroprotective and antiarthritic effects of daphnetin used in vitro and in vivo osteoarthritis models.
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DOI：
10.1016/j.lfs.2019.116857
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发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Xiaohan Zhang;Jun Yao;Zhengyuan Wu;Kai Zou;Zhenyi Yang;Xing Huang;Zhiwei Luan;Jia Li;Qingjun Wei
中科院分区：
文献类型：
--
作者：
Xiaohan Zhang;Jun Yao;Zhengyuan Wu;Kai Zou;Zhenyi Yang;Xing Huang;Zhiwei Luan;Jia Li;Qingjun Wei
aimsaphnetin （DAP）是一种常用的治疗心血管疾病的中药。研究证实DAP具有抗炎、抗氧化、抗菌杀虫、抗肿瘤和神经保护作用。然而，其抗关节炎的潜力仍未被发掘。本研究的目的是研究DAP的体外保护作用。主要方法采用重组人IL-1β 24 h检测DAP对兔原代软骨细胞的影响。将家兔随机分为正常对照组和骨关节炎组。OA组接受三种不同剂量的DAP，疗程为4周或8周。采用组织病理学检查、qRT-PCR、免疫印迹和免疫组化分析评价DAP的抗关节炎作用。在体外实验结果表明，DAP对软骨细胞IL-1β具有保护作用。在体外，DAP抑制IL-1β诱导的兔软骨细胞中IL-6、IL-12、MMP-3、MMP-9和MMP-13的表达，并刺激IL-10的产生。DAP对MMPs的抑制作用部分通过抑制PI3K/AKT、MAPK和NF-κB信号通路来调节。DAP对OA的作用可能与抑制炎症因子分泌、促凋亡Caspase-3和BAX减少观察到的软骨细胞凋亡、激活抗凋亡BCL-2有关。意义ap在OA治疗中具有广阔的应用前景，为OA提供了一种新的治疗策略。
AimsDaphnetin (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 thein vitroandin vivochondroprotective effects of DAP.Main methodsThe effect of DAP on primary rabbit chondrocytes was examined using recombinant human IL-1β for 24 h. For thein vivostudies, 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.Key findingsBothin vitroandin vivoresults 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.SignificanceDAP has a broad range of prospects in the treatment of OA, which provides a novel therapeutic strategy for OA.