A molecular docking study: Cepharanthine protects articular cartilage against arthritis by Wnt/PI3K/TLR-3 signaling

• Main Authors: Wenmin Zhao, Dongyun Yao, Ru Yang, Heshui Huo, Chenman Qin, Kai Sun
• Format: Article
• Language: English
• Published: Elsevier 2021-02-01
• Series: Arabian Journal of Chemistry
• Subjects: Cepharanthine; Rheumatoid arthritis; Chondrocytes; Autophagy; Inflammation
• Online Access: http://www.sciencedirect.com/science/article/pii/S1878535220304354

Rheumatoid arthritis (RA) is an autoimmune disorder that causes joint inflammation and permanent disability in affected patients. This study investigated the protective effect of cepharanthine treatment against Freund's adjuvant-induced RA in a rat model. RA was induced in rats by injection of incomplete Freund’s adjuvant (IFA) into the plantar surface on days 0 and 9. Cepharanthine at a dose of 10 or 20 mg/kg was administered intraperitoneally to separate groups of rats 12 days after the administration of IFA. The effects of cepharanthine on RA were determined by measuring serum biochemical parameters, blood cell counts and serum inflammatory and oxidative stress mediators. The expression levels of several proteins that regulate the Wnt/PI3K/Toll-like receptor (TLR)-3 pathway were measured via immunohistochemistry, western blotting and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) assays. Molecular docking was performed to assess the interactions of cepharanthine with Wnt, PI3K and TLR-3 proteins. Our data revealed that cepharanthine treatment attenuated serum biochemical parameters, blood cell counts and serum inflammatory and oxidative stress mediators in RA rats. Analyses with qRT-PCR and western blotting revealed that the mRNA expression levels of Wnt/PI3K/TLR-3 pathway components were attenuated in cepharanthine-treated RA rats. Cepharanthine also reduced chondrocyte apoptosis and autophagy. Molecular docking analysis revealed significant interactions of cepharanthine with Wnt, PI3K and TLR-3 proteins. In conclusion, the findings implied that cepharanthine treatment attenuates chondrocyte autophagy, apoptosis and proliferation by regulating the Wnt/PI3K/TLR-3 pathway in RA rats.