title: Icariin attenuates hypoxia-induced oxidative stress and apoptosis in osteoblasts and preserves their osteogenic differentiation potential in vitro.
abstract: OBJECTIVE
  Icariin, a prenylated flavonol glycoside isolated from traditional Chinese medicinal herb of the genus Epimedium, has been demonstrated to be a potential alternative therapy for osteoporosis, and its action mechanism so far has been mainly attributed to its phytoestrogenic property. As blood supply to bone is considerably reduced with ageing and by the menopause, we hypothesized that icariin treatment would reduce bone loss by preventing ischaemia-induced hypoxic damages to bone.
  
  
  METHODS
  To investigate effects of icariin treatment on cultured rat calvarial osteoblasts exposed to hypoxic conditions (2% oxygen).
  
  
  RESULTS
  Compared to normoxic control, cell viability decreased with time to 50% by 48 h in the hypoxic group, and icariin attenuated the reduction, dose dependently, with 10(-6) and 10(-5)  m concentrations showing significant protective effects. Icariin also inhibited increase of lactate dehydrogenase activity in culture media. Measurements on oxidative stress, cell cycling and cell survival indicated that icariin protected osteoblasts by reducing production of reactive oxygen species and malondialdehyde, increasing superoxide dismutase activity, arresting the cell cycle and inhibiting apoptosis. Icariin also preserved osteogenic differentiation potential of the hypoxic cells in a dose-dependent manner, compared to the hypoxia alone group, as revealed by increased levels of RUNX-2, OSX and BMP-2 gene expression, alkaline phosphatase activity, and formation of mineralized nodules.
  
  
  CONCLUSIONS
  Our results demonstrated that icariin attenuated oxidative stress and apoptosis and preserved viability and osteogenic potential of osteoblasts exposed to hypoxia in vitro, and suggested that its anti-osteoporotic effect may be attributed to its anti-hypoxic activity and phytoestrogenic properties.
authors.affiliation: Department of Pharmacy, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou, 730050, China.
authors.forename: H-P
authors.initials: HP
authors.lastname: Ma
authors.forename: X-N
authors.initials: XN
authors.lastname: Ma
authors.forename: B-F
authors.initials: BF
authors.lastname: Ge
authors.forename: P
authors.initials: P
authors.lastname: Zhen
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: Y-H
authors.initials: YH
authors.lastname: Gao
authors.forename: C J
authors.initials: CJ
authors.lastname: Xian
authors.forename: K-M
authors.initials: KM
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D034181:Epimedium / Q000737:chemistry / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D008315:Malondialdehyde / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010012:Osteogenesis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012886:Skull / Q000166:cytology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D018809:Proliferating Cell Nuclear Antigen; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D013482:Superoxide Dismutase; C056599:icariin