title: Comparative proteomic and metabolomic analysis reveal the antiosteoporotic molecular mechanism of icariin from Epimedium brevicornu maxim.
abstract: BACKGROUND
  Icariin, a principal flavonoid glycoside of Epimedium brevicornu Maxim, has been widely proved to possess antiosteoporotic activity with promoting bone formation and decreasing bone resorption. However, the involving mechanisms remain unclear.
  
  
  OBJECTIVE
  To clear a global insight of signal pathways involved in anti-osteoporotic mechanism of icariin at proteins and metabolites level by integrating the proteomics and NMR metabonomics, in a systems biology approach.
  
  
  METHODS
  Mice were divided into sham, OVX model and icariin-treated OVX group, after 90 days treatment, difference gel electrophoresis combined with MALDI-TOF/TOF proteomics analysis on bone femur and serum metabolomics were carried out for monitor intracellular processes and elucidate anti-osteoporotic mechanism of icariin. Osteoblast and osteoclast were applied to evaluate the potential signal pathways.
  
  
  RESULTS
  Twenty three proteins in bone femur, and 8 metabolites in serum, were significantly altered and identified, involving in bone remodeling, energy metabolism, cytoskeleton, lipid metabolism, MAPK signaling, Ca2+signaling et, al. Furthermore, animal experiment show icariin could enhance the BMD and BMC, decrease CTX-I level in ovariectomized mice. The mitochondrial membrane potential and the intracellular ATP levels were increased significantly, and the cytoskeleton were improved in icariin-treatment osteoblast and osteoclast. Icariin also increased mRNA expression of Runx2 and osterix of OB, decreased CTR and CAII mRNA expression and protein expression of P38 and JNK. However, icariin did not reveal any inhibition of the collagenolytic activity of cathepsin K, mRNA expression of MMP-9 and protein expression of ERK in osteoclast.
  
  
  CONCLUSIONS
  we consider icariin as multi-targeting compounds for treating with osteoporosis, involve initiating osteoblastogenesis, inhibiting adipogenesis, and preventing osteoclast differentiation.
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Institute of Chemical Toxicity, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; Department of Oral Biological and Medical Sciences, The University of British Columbia, Vancouver, BC, Canada V6T1Z3.
authors.forename: Liming
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Han
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Naidan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: qinluping@126.com.
authors.forename: Luping
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: hangliangxin@163.con.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Xin
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: zqy1965@163.com.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000302:isolation & purification / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D034181:Epimedium / Q000737:chemistry*; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D055432:Metabolomics / Q000379:methods; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D040901:Proteomics / Q000379:methods; D066244:Proton Magnetic Resonance Spectroscopy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D005419:Flavonoids; D010936:Plant Extracts; D012333:RNA, Messenger; C056599:icariin
keywords: Bone metabolism; Metabolomics; Osteoporosis; Proteomics