title: Icaritin requires Phosphatidylinositol 3 kinase (PI3K)/Akt signaling to counteract skeletal muscle atrophy following mechanical unloading.
abstract: Counteracting muscle atrophy induced by mechanical unloading/inactivity is of great clinical need and challenge. A therapeutic agent that could counteract muscle atrophy following mechanical unloading in safety is desired. This study showed that natural product Icaritin (ICT) could increase the phosphorylation level of Phosphatidylinositol 3 kinase (PI3K) at p110 catalytic subunit and promote PI3K/Akt signaling markers in C2C12 cells. This study further showed that the high dose ICT treatment could significantly attenuate the decreases in the phosphorylation level of PI3K at p110 catalytic subunit and its downstream markers related to protein synthesis, and inhibit the increases in protein degradation markers at mRNA and protein levels in rat soleus muscle following 28-day hindlimb unloading. In addition, the decreases in soleus muscle mass, muscle fiber cross-sectional area, twitch force, specific force, contraction time and half relaxation time could be significantly attenuated by the high dose ICT treatment. The low dose ICT treatment could moderately attenuate the above changes induced by unloading. Wortmannin, a specific inhibitor of PI3K at p110 catalytic subunit, could abolish the above effects of ICT in vitro and in vivo, indicating that PI3K/Akt signaling could be required by ICT to counteract skeletal muscle atrophy following mechanical unloading.
authors.affiliation: School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, 518057, China.
authors.forename: Zong-Kang
authors.initials: ZK
authors.lastname: Zhang
authors.affiliation: School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, 518057, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Baosheng
authors.initials: B
authors.lastname: Guo
authors.affiliation: School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, 518057, China.
authors.forename: Albert
authors.initials: A
authors.lastname: Leung
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, 518057, China.
authors.forename: Bao-Ting
authors.initials: BT
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D004195:Disease Models, Animal; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D009133:Muscular Atrophy / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014176:Protein Biosynthesis; D021122:Protein Subunits / Q000378:metabolism; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D005419:Flavonoids; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D021122:Protein Subunits; D051057:Proto-Oncogene Proteins c-akt; C499403:icaritin
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