title: Hesperidin derivative-11 inhibits fibroblast-like synoviocytes proliferation by activating Secreted frizzled-related protein 2 in adjuvant arthritis rats.
abstract: 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.
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Junda
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China. Electronic address: lj@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006569:Hesperidin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000070918:Synoviocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D006569:Hesperidin; D008565:Membrane Proteins; C503650:Sfrp2 protein, rat; D000094742:Secreted Frizzled-Related Proteins
keywords: Acetone (PubChem CID: 180); DNA methyltransferase 1; Ethylene Diamine Tetraacetic Acid (PubChem CID: 6049); Formaldehyde (PubChem CID: 712); Hesperidin (PubChem CID: 53477767); Hesperidin derivative-11; Proliferation; Rheumatoid arthritis; Secreted frizzled-related protein 2; Triton X-100(PubChem CID: 5590); Wnt/β-catenin signaling