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Asiatic acid inhibits rheumatoid arthritis fibroblast‐like synoviocyte growth through the Nrf2/HO‐1/NF‐κB signaling pathway
Chemical Biology & Drug Design ( IF 3 ) Pub Date : 2024-03-13 , DOI: 10.1111/cbdd.14454
Li Zhang 1 , Zhi‐ning Liu 1, 2 , Xi‐yuan Han 1 , Xin Liu 1, 3 , Yang Li 1
Affiliation  

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‐κB 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‐κB protein expression. However, the knockdown of Nrf2 significantly offsets the effects of AA on the proliferation, apoptosis, and Nrf2/HO‐1/NF‐κB 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‐κB pathway.

中文翻译:

积雪草酸通过Nrf2/HO-1/NF-κB信号通路抑制类风湿关节炎成纤维细胞样滑膜细胞生长

积雪草酸(AA)在多种疾病的治疗中被普遍认可,在多种炎症性疾病的治疗中具有显着的优势。用 AA 治疗类风湿性关节炎 (RA) 是一个全新的切入点。RA是一种复杂的自身免疫性炎症性疾病,尽管RA的发病机制涉及不同的免疫和非免疫细胞,但成纤维细胞样滑膜细胞(FLS)在疾病的进展中发挥着至关重要的作用。si-Nrf2 转染 RA-FLS 并用 AA 处理细胞。MTT法和集落形成法分别检测AA对RA-FLS活力和克隆形成的影响。此外,通过Hoechst 33342染色和流式细胞术观察RA-FLS的凋亡情况。Western blot检测Nrf2/HO-1/NF-κB信号通路相关蛋白的表达。与对照组相比,AA浓度的增加显着抑制了RA-FLS的增殖和克隆形成,进一步实验表明AA诱导RA-FLS凋亡。此外,AA还激活Nrf2/HO-1通路,抑制NF-κB蛋白表达。然而,Nrf2的敲低显着抵消了AA对RA-FLS细胞增殖、凋亡和Nrf2/HO-1/NF-κB信号通路的影响。AA可以通过抑制RA-FLS增殖并诱导其凋亡来治疗RA。其机制可能与Nrf2/HO-1/NF-κB通路的激活有关。
更新日期:2024-03-13
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