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Comparative proteomic and metabolomic analysis reveal the antiosteoporotic molecular mechanism of icariin from Epimedium brevicornu maxim

Xue, Liming, Jiang, Yiping, Han, Ting, Zhang, Naidan, Qin, Luping, Xin, Hailiang, Zhang, Qiaoyan
Journal of ethnopharmacology 2016 v.192 pp. 370-381
Epimedium brevicornu, adenosine triphosphate, adipogenesis, blood serum, bone formation, bone resorption, calcium, cathepsin K, cytoskeleton, energy metabolism, femur, gel electrophoresis, gene expression, glycosides, icariin, laboratory animals, lipid metabolism, membrane potential, messenger RNA, metabolites, metabolomics, mice, mitochondrial membrane, mitogen-activated protein kinase, models, nuclear magnetic resonance spectroscopy, osteoblasts, osteoclasts, osteoporosis, ovariectomy, protein synthesis, proteins, proteomics, signal transduction, traditional medicine
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.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.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.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.we consider icariin as multi-targeting compounds for treating with osteoporosis, involve initiating osteoblastogenesis, inhibiting adipogenesis, and preventing osteoclast differentiation.