title: Selective modulation of MAPKs contribute to the anti-proliferative and anti-inflammatory activities of 1,7-dihydroxy-3,4-dimethoxyxanthone in rheumatoid arthritis-derived fibroblast-like synoviocyte MH7A cells.
abstract: BACKGROUND
  1,7-Dihydroxy-3,4-dimethoxyxanthone (XAN) is an antirheumatic agent isolated from traditional Chinese medicine Securidaca inappendiculata Hassk. This study was designed to investigate its anti-proliferative and anti-inflammatory activities on rheumatoid arthritis derived fibroblast-like synoviocyte cell line MH7A, and explore the underlying mechanism of action.
  
  
  METHODS
  The anti-proliferative activity of XAN on MH7A cells was assessed by an MTT method. Its pro-apoptotic and cell cycle arrest activities were analyzed by flow cytometry. W-B method was employed to investigate hallmark kinases involved in the course. Pro-inflammatory cytokines in culture supernatant of MH7A cells were determined by an ELISA method.
  
  
  RESULTS
  The results showed XAN efficiently suppressed the proliferation and secretion of IL-1β and IL-6 of MH7A cells in a concentration-dependent manner. Co-treatment with MAPKs inhibitors U0126, SB202190 and SP600125 indicated JNK and p38 pathways were involved in the course. Up-regulation of p-p38, p-ERK, bax and p21, and down-regulation of p-JNK, cyclin D1 and bcl-2 were observed upon the treatment with XAN. SB202190 partly reversed the modulatory effects. The results suggested XAN inhibited the proliferation of MH7A cells mainly via cell cycle arrest at G1/S phase, and the activity was due to the up-regulation of p-p38, which led to the modulation of p21 and cyclin D1. The down-regulation of p-JNK by XAN suppressed the secretion of pro-inflammatory cytokines, which was beneficial to the anti-proliferative activity of MH7A cells.
  
  
  CONCLUSIONS
  XAN selectively modulated MAPKs signaling, and exerted the subsequent anti-proliferative and anti-inflammatory activities on MH7A cells.
authors: College of Pharmacy, Nanjing University of Chinese Medicine, PR China; Department of Pharmacy, Yijishan Affiliated Hospital of Wannan Medical College, PR China.
authors: Jian
authors: J
authors: Zuo
authors: College of Pharmacy, Nanjing University of Chinese Medicine, PR China.
authors: Yan
authors: Y
authors: Xia
authors: College of Pharmacy, Nanjing University of Chinese Medicine, PR China. Electronic address: lixiang_8182@163.com.
authors: Xiang
authors: X
authors: Li
authors: School of Pharmacy, Jiangsu University, PR China. Electronic address: zhenouyang@ujs.edu.cn.
authors: Zhen
authors: Z
authors: Ou-Yang
authors: College of Pharmacy, Nanjing University of Chinese Medicine, PR China.
authors: Jian-wei
authors: JW
authors: Chen
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013583:Synovial Membrane / Q000166:cytology; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D047428:Protein Kinase Inhibitors; D044004:Xanthones; C031188:veratrilogenin; D020928:Mitogen-Activated Protein Kinases
keywords: 1,7-dihydroxy-3,4-dimethoxyxanthone; G(1)/S arrest; MAPK; MH7A cells; Rheumatoid arthritis (RA); Securidaca inappendiculata