Lim Jeong Ho, Ahmad Syed Sayeed, Hwang Ye Chan, Baral Ananda, Hur Sun Jin, Lee Eun Ju, Choi Inho
Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Int J Mol Sci. 2025 Jan 2;26(1):345. doi: 10.3390/ijms26010345.
Cultured meat (CM) is derived from the in vitro myogenesis of muscle satellite (stem) cells (MSCs) and offers a promising alternative protein source. However, the development of a cost-effective media formulation that promotes cell growth has yet to be achieved. In this study, laxogenin (LAX) and 5-alpha-hydroxy-laxogenin (5HLAX) were computationally screened against myostatin (MSTN), a negative regulator of muscle mass, because of their antioxidant properties and dual roles as MSTN inhibitors and enhancers of myogenesis regulatory factors. In silico analysis showed LXG and 5HLXG bound to MSTN with binding free energies of -7.90 and -8.50 kcal/mol, respectively. At a concentration of 10 nM, LAX and 5HLAX effectively inhibited the mRNA and protein expressions of MSTN, promoted myogenesis, and enhanced myotube formation and maturation. In addition, by acting as agonists of ROS downregulating factors, they exhibited antioxidative effects. This study shows that supplementation with LAX or 5HLAX at 10 nM in CM production improves texture, quality, and nutritional value. We believe this study fills a research gap on media development for myotube formation and maturation, which are important factors for large-scale in vitro CM production that improve product quality, nutritional value, and efficacy.
培养肉（CM）源自肌肉卫星（干）细胞（MSCs）的体外肌生成，是一种很有前景的替代蛋白质来源。然而，开发一种促进细胞生长且具有成本效益的培养基配方仍未实现。在本研究中，由于泻根醇（LAX）和5-α-羟基泻根醇（5HLAX）具有抗氧化特性，且兼具肌肉生长抑制素（MSTN，一种肌肉量的负调节因子）抑制剂和成肌调节因子增强剂的双重作用，因此对其针对MSTN进行了计算机筛选。计算机模拟分析表明，LXG和5HLXG与MSTN结合，结合自由能分别为-7.90和-8.50千卡/摩尔。在10 nM的浓度下，LAX和5HLAX有效抑制了MSTN的mRNA和蛋白质表达，促进了成肌作用，并增强了肌管的形成和成熟。此外，它们作为活性氧下调因子的激动剂，表现出抗氧化作用。本研究表明，在CM生产中添加10 nM的LAX或5HLAX可改善质地、质量和营养价值。我们相信，这项研究填补了关于肌管形成和成熟的培养基开发方面的研究空白，而肌管形成和成熟是大规模体外CM生产中提高产品质量、营养价值和功效的重要因素。
