Hesperidin derivative-11 inhibits fibroblast-like synoviocytes proliferation by activating Secreted frizzled-related protein 2 in adjuvant arthritis rats

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• 关键词：Hesperidin (PubChem CID ; 53477767) ; Formaldehyde (PubChem CID ; 712) ; Acetone (PubChem CID ; 180) ; Triton X-100(PubChem CID ; 5590) ; Ethylene Diamine Tetraacetic Acid (PubChem CID ; 6049)
• 刊名：European Journal of Pharmacology
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：794
• 期：Complete
• 页码：173-183
• 全文大小：1864 K
• 卷排序：794

文摘

Hesperidin (HDN), a flavanone glycoside derived from the citrus cultivation, has a multitude of pharmacological properties, which include antioxidant, anti-inflammatory, hypolipidaemic and anti-carcinogenic actions, but the underlying mechanisms by which treatment of HDN attenuates Rheumatoid Arthritis (RA) remain elusive. Here we engaged to determine whether Hesperidin derivative-11(HDND-11), a HDN derivative with enhanced water-solubility and bioavailability, is effective on treating arthritis in rats. In this study, results of 3-(4, 5-dimethylthiazol-2-yl)−2, 5-diphenyltetra-zolium bromide (MTT) assay and Flow cytometry indicated that administration of HDND-11 inhibited proliferation of fibroblast-like synoviocytes (FLS). Results of Western blot, Real-time quantitative PCR (RT-qPCR) analysis and Immunofluorescence staining demonstrated that HDND-11 was able to up-regulate the expression of Secreted frizzled-related proteins 2 (SFRP2) and diminish DNA methyltransferase 1(DNMT1) expression. We also identified that the effect of DNMT1 inhibition was completely similar to the effects of HDND-11 on SFRP2 gene expression. Furthermore, our results indicated that treatment with HDND-11 could suppress activation of Wnt pathway. Taken together, we found that the HDND-11diminished inhibitory effect of DNMT1 on SFRP2, thereby down-regulated β-catenin expression and inhibited the activation of Wnt signaling pathways to inhibit FLS growth.