title: Herbal composition of Cinnamomum cassia, Pinus densiflora, Curcuma longa and Glycyrrhiza glabra prevents atherosclerosis by upregulating p27 (Kip1) expression.
abstract: BACKGROUND
  Kiom-18 is a novel composition of Cinnamomum cassia, Pinus densiflora, Curcuma longa and Glycyrrhiza glabra. Curcuma longa and Glycyrrhiza glabra, which are traditional medicines in Asia, have been reported to demonstrate preventive effects against atherosclerosis; however, they have not yet been developed into functional atherosclerosis treatments. We therefore studied the anti-atherosclerotic effects and possible molecular mechanisms of Kiom-18 using vascular smooth muscle cells (VSMCs).
  
  
  METHODS
  To assess the anti-proliferative effect of Kiom-18 in vitro, we performed thymidine incorporation, cell cycle progression, immunoblotting and immunofluorescence assays in VSMCs stimulated by platelet derived-growth factor (PDGF)-BB. In addition, we used LDLr knockout mice to identify the effects of Kiom-18 as a preliminary result in an atherosclerosis animal model.
  
  
  RESULTS
  Kiom-18 inhibited platelet-derived growth factor (PDGF)-BB-stimulated-VSMC proliferation and DNA synthesis. Additionally, Kiom-18 arrested the cell cycle transition of G0/G1 stimulated by PDGF-BB and its cell cycle-related proteins. Correspondingly, the level of p27(kip1) expression was upregulated in the presence of the Kiom-18 extract. Moreover, in an atherosclerosis animal model of LDLr knockout mice, Kiom-18 extract showed a preventive effect for the formation of atherosclerotic plaque and suppressed body weight, fat weight, food treatment efficiency, neutrophil count, and triglyceride level.
  
  
  CONCLUSIONS
  These results indicate that Kiom-18 exerts anti-atherosclerotic effects by inhibiting VSMC proliferation via G0/G1 arrest, which upregulates p27(Kip1) expression.
authors.affiliation: Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu, 701-300, Republic of Korea.
authors.forename: Jung-Jin
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu, 701-300, Republic of Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu, 701-300, Republic of Korea.
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Cho
authors.affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon, 305-764, Republic of Korea.
authors.forename: Joo-Hui
authors.initials: JH
authors.lastname: Han
authors.affiliation: Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu, 701-300, Republic of Korea. jyma@kiom.re.kr.
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
mesh_terms: D000818:Animals; D001011:Aorta; D050197:Atherosclerosis / Q000378:metabolism / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D032904:Cinnamomum aromaticum / Q000737:chemistry*; D030024:Curcuma / Q000737:chemistry*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D006035:Glycyrrhiza / Q000737:chemistry*; D051379:Mice; D018345:Mice, Knockout; D028223:Pinus / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D010936:Plant Extracts; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Anti-atherosclerotic activity; Cell cycle; Cyclin-dependent kinase inhibitor; Kiom-18; Vascular smooth muscle cell