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Ginsenoside Rb1 and Rb2 upregulate Akt/mTOR signaling?mediated muscular hypertrophy and myoblast differentiation

Journal of Ginseng Research 2020년 44권 3호 p.435 ~ 441
고가연 ( Go Ga-Yeon ) - Sookmyung Women’s University College of Pharmacy

조아영 ( Jo A-Young ) - Sookmyung Women’s University College of Pharmacy
서동완 ( Seo Dong-Wan ) - Dankook University College of Pharmacy
김우영 ( Kim Woo-Young ) - Sookmyung Women’s University College of Pharmacy
김영기 ( Kim Yong-Kee ) - Sookmyung Women’s University College of Pharmacy
 ( So Eui-Young ) - Brown University Alpert Medical School Rhode Island Hospital Department of Medicine
 ( Chen Qian ) - Brown University Alpert Medical School Rhode Island Hospital Department of Orthopaedics
강종선 ( Kang Jong-Sun ) - Sungkyunkwan University Department of Molecular Cell Biology
배규운 ( Bae Gyu-Un ) - Sookmyung Women’s University College of Pharmacy
이상진 ( Lee Sang-Jin ) - Sookmyung Women’s University College of Pharmacy

Abstract


Background: As a process of aging, skeletal muscle mass and function gradually decrease. It is reported that ginsenoside Rb1 and Rb2 play a role as AMP-activated protein kinase activator, resulting in regulating glucose homeostasis, and Rb1 reduces oxidative stress in aged skeletal muscles through activating the phosphatidylinositol 3-kinase/Akt/Nrf2 pathway. We examined the effects of Rb1 and Rb2 on differentiation of the muscle stem cells and myotube formation.

Methods: C2C12 myoblasts treated with Rb1 and/or Rb2 were differentiated and induced to myotube formation, followed by immunoblotting for myogenic marker proteins, such as myosin heavy chain, MyoD, and myogenin, or immunostaining for myosin heavy chain or immunoprecipitation analysis for heterodimerization of MyoD/E-proteins.

Results: Rb1 and Rb2 enhanced myoblast differentiation through accelerating MyoD/E-protein heterodimerization and increased myotube hypertrophy, accompanied by activation of Akt/mammalian target of rapamycin signaling. In addition, Rb1 and Rb2 induced the MyoD-mediated transdifferentiation of the rhabdomyosarcoma cells into myoblasts. Furthermore, co-treatment with Rb1 and Rb2 had synergistically enhanced myoblast differentiation through Akt activation.

Conclusion: Rb1 and Rb2 upregulate myotube growth and myogenic differentiation through activating Akt/mammalian target of rapamycin signaling and inducing myogenic conversion of fibroblasts. Thus, our first finding indicates that Rb1 and Rb2 have strong potential as a helpful remedy to prevent and treat muscle atrophy, such as age-related muscular dystrophy.

키워드

Akt/mTOR signaling; Hypertrophy; Myoblast differentiation; Rb1; Rb2
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