Asiatic acid inhibits rheumatoid arthritis fibroblast-like synoviocyte growth through the Nrf2/HO-1/NF-B signaling pathway

CHEMICAL BIOLOGY & DRUG DESIGN(2024)

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摘要
Asiatic acid (AA) is generally recognized in the treatment of various diseases and has significant advantages in the treatment of various inflammatory diseases. The treatment of rheumatoid arthritis (RA) with AA is a completely new entry point. RA is a complex autoimmune inflammatory disease, and despite the involvement of different immune and nonimmune cells in the pathogenesis of RA, fibroblast-like synoviocytes (FLS) play a crucial role in the progression of the disease. si-Nrf2 was transfected in RA-FLS and the cells were treated with AA. MTT assay and colony formation assay were used to detect the effect of AA on the viability and formation of clones of RA-FLS, respectively. Moreover, the apoptosis of RA-FLS was observed by Hoechst 33342 staining and flow cytometry. Western blot was applied to measure the expression of the Nrf2/HO-1/NF-kappa B signaling pathway-related proteins. Compared with the control group, RA-FLS proliferation, and clone formation were significantly inhibited by the increase of AA concentration, and further experiments showed that AA-induced apoptosis of RA-FLS. In addition, AA activated the Nrf2/HO-1 pathway to inhibit NF-kappa B protein expression. However, the knockdown of Nrf2 significantly offsets the effects of AA on the proliferation, apoptosis, and Nrf2/HO-1/NF-kappa B signaling pathway of RA-FLS cells. AA can treat RA by inhibiting the proliferation and inducing the apoptosis of RA-FLS. The mechanism may be related to the activation of the Nrf2/HO-1/NF-kappa B pathway. si-Nrf2 was transfected in RA-FLS and the cells were treated with AA. The effect of AA on the activity of RA-FLS cells was detected by MTT assay. The effect of AA on human RA-FLS cloning was detected by a colony formation test. The apoptosis of RA-FLS cells was observed by Hoechst 33342 staining. The effect of AA on apoptosis of RA-FLS cells was detected by flow cytometry. Western blot analysis was performed to detect apoptosis and NF-kappa B/Nrf2/HO-1 signaling pathway-related protein expression. Our results suggest that AA can inhibit the proliferation of RA-FLS cells and induce apoptosis in the treatment of RA, which may be related to the activation of the Nrf2/HO-1/NF-kappa B pathway.image
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关键词
apoptosis,asiatic acid,fibroblast-like synoviocytes,proliferation,rheumatoid arthritis
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