Go Ga-Yeon, Jo Ayoung, Seo Dong-Wan, Kim Woo-Young, Kim Yong Kee, So Eui-Young, Chen Qian, Kang Jong-Sun, Bae Gyu-Un, Lee Sang-Jin
Research Institute of Pharmaceutical Science, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
College of Pharmacy, Dankook University, Cheonan, Republic of Korea.
J Ginseng Res. 2020 May;44(3):435-441. doi: 10.1016/j.jgr.2019.01.007. Epub 2019 Jan 31.
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.
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.
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.
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.
作为衰老过程，骨骼肌质量和功能会逐渐下降。据报道，人参皂苷Rb1和Rb2作为AMP激活的蛋白激酶激活剂发挥作用，从而调节葡萄糖稳态，并且Rb1通过激活磷脂酰肌醇3激酶/蛋白激酶B/核因子E2相关因子2通路来降低衰老骨骼肌中的氧化应激。我们研究了Rb1和Rb2对肌肉干细胞分化和肌管形成的影响。
用Rb1和/或Rb2处理C2C12成肌细胞，使其分化并诱导形成肌管，随后对肌球蛋白重链、肌分化抗原（MyoD）和生肌调节因子等生肌标志物蛋白进行免疫印迹分析，或对肌球蛋白重链进行免疫染色，或对MyoD/E蛋白异二聚化进行免疫沉淀分析。
Rb1和Rb2通过加速MyoD/E蛋白异二聚化增强成肌细胞分化，并增加肌管肥大，同时伴有蛋白激酶B/雷帕霉素靶蛋白信号通路的激活。此外，Rb1和Rb2诱导横纹肌肉瘤细胞由MyoD介导转分化为成肌细胞。此外，Rb1和Rb2联合处理通过激活蛋白激酶B协同增强成肌细胞分化。
Rb1和Rb2通过激活蛋白激酶B/雷帕霉素靶蛋白信号通路并诱导成纤维细胞的生肌转化来上调肌管生长和生肌分化。因此，我们的首个发现表明，Rb1和Rb2具有预防和治疗肌肉萎缩（如年龄相关性肌营养不良症）的强大潜力。
