Chondroprotective and antiarthritic effects of Daphnetin used in vitro and in vivo osteoarthritis models

• Published in: Life sciences (1973) 2020-01, Vol.240, p.116857-116857, Article 116857
• Main Authors: Zhang, Xiaohan, Yao, Jun, Wu, Zhengyuan, Zou, Kai, Yang, Zhenyi, Huang, Xing, Luan, Zhiwei, Li, Jia, Wei, Qingjun
• Format: Article
• Language: English
• Subjects: Animals; Anti-arthritic; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Apoptosis - drug effects; Cartilage, Articular - drug effects; Cartilage, Articular - pathology; Cell Survival; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - pathology; Chondroprotective; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Daphnetin; Dose-Response Relationship, Drug; Interleukin-1beta - pharmacology; Male; Osteoarthritis; Osteoarthritis - drug therapy; Osteoarthritis - pathology; Primary Cell Culture; Protective Agents - therapeutic use; Rabbits; Signal Transduction - drug effects; Umbelliferones - adverse effects; Umbelliferones - therapeutic use
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.116857

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.