title: Glabretal-type triterpenoid from the root bark of Dictamnus dasycarpus ameliorates collagen-induced arthritis by inhibiting Erk-dependent lymphocyte proliferation.
abstract: BACKGROUND
  The root bark of Dictamnus dasycarpus Turcz. (Rutaceae) has been used as a traditional herbal medicine to treat various inflammatory diseases in East Asia. We have showed previously that a glabretal type triterpenoid (dictabretol A) from D. dasycarpus root bark has immunosuppressive activity.
  
  
  OBJECTIVE
  This study was conducted to define the molecular mechanism of how dictabretol A inhibits lymphocyte proliferation and to evaluate the therapeutic efficacy of dictabretol A in an animal model of rheumatoid arthritis.
  
  
  METHODS
  Various murine immune cells (T cells, B cells, and macrophages) and splenocytes were used to study the anti-proliferative effect of dictabretol A in vitro. A collagen-induced arthritis model was also used to examine the therapeutic effect of dictabretol A in vivo.
  
  
  RESULTS
  Dictabretol A specifically inhibited lymphocyte proliferation by blocking the cell cycle transition from the G1 to the S phase. This effect was achieved by blocking Erk1/2, nuclear factor kappa B, and the C-myc axis of cell cycle progression. Further dictabretol A treatment alleviated the severity of collagen-induced arthritis.
  
  
  CONCLUSIONS
  Our results reveal the molecular mechanism for the anti-lymphoproliferative effect of dictabretol A and show the therapeutic efficacy of dictabretol A for rheumatoid arthritis.
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Sang-Pil
authors.initials: SP
authors.lastname: Choi
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Chang-Yong
authors.initials: CY
authors.lastname: Choi
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Kyungmin
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Nahyun
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Hyun-Seuk
authors.initials: HS
authors.lastname: Moon
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea. Electronic address: dongholee@korea.ac.kr.
authors.forename: Dongho
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea. Electronic address: tchun@korea.ac.kr.
authors.forename: Taehoon
authors.initials: T
authors.lastname: Chun
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D036905:Dictamnus / Q000737:chemistry*; D016193:G1 Phase / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D016271:Proto-Oncogene Proteins c-myc; D014315:Triterpenes; D003094:Collagen
keywords: Cell cycle; Collagen induced arthritis; Dictabretol A; Lymphocyte; Signal transduction