title: Effect of orally ingested diosgenin into diet on skin collagen content in a low collagen skin mouse model and its mechanism of action.
abstract: OBJECTIVE
  Influence on collagen content with oral ingestion of diosgenin (Dios) was investigated in established low collagen skin mouse model. And its mechanism of action was investigated using primary cultured fibroblasts.
  
  
  METHODS
  Hairless mice were fed a low protein diet with Dios for 8weeks and the contents of collagen in skin were determined by measuring the content of hydroxyproline (Hyp). In primary cultured fibroblasts, the numbers of fibroblast were determined by incubating with Dios for 120h; the contents of Hyp were determined by incubating with Dios for 24 or 72h using fibroblasts of confluent state; the expressions of messenger ribonucleic acid (mRNA) were determined by incubating with Dios for 24h.
  
  
  RESULTS
  Oral ingestion of Dios in the diet for 8weeks led to a dose-dependent increase in the Hyp content as collagen content of skin. In proliferating of primary cultured fibroblasts, Dios treatment led to a decrease of adenosine 5'-triphosphate content indicating decrease of the cell number. In the cells reached to confluent, although increase of Hyp content in the control indicating progress of fibroblasts differentiation were observed, the content of Hyp remained unchanged with Dios treatment. Finally, addition of Dios led to a decrease the α-tubulin and c-fos mRNA expressions relating to the cell cycle.
  
  
  CONCLUSIONS
  It is concluded that Dios can improve skin collagen content by shifting the dynamics of the fibroblasts from proliferation to differentiation via cell cycle arrest.
authors.affiliation: Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Haratake
authors.affiliation: Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. Electronic address: watase@fukuoka-u.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watase
authors.affiliation: Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Setoguchi
authors.affiliation: Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Nagata-Akaho
authors.affiliation: Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Matsunaga
authors.affiliation: Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Takata
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects / Q000378:metabolism*; D004032:Diet; D004144:Diosgenin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004435:Eating; D005247:Feeding Behavior; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014404:Tubulin; D003094:Collagen; D004144:Diosgenin
keywords: Diosgenin; Low collagen skin mouse model; Oral ingestion; Primary cultured fibroblast; Skin collagen content