Department of Biomaterials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea.
R&D Center, FND Net, Seoul 05706, Republic of Korea.
J Microbiol Biotechnol. 2020 Dec 28;30(12):1896-1904. doi: 10.4014/jmb.2005.05023.
Muscle atrophy, characterized by a reduced number and size of myofibers, occurs due to immobilization, aging, and several chronic diseases. , belonging to the Labiatae family, is widely used as a traditional medicine in Korea, China, and Japan. Previous studies have reported that has various physiological activities, such as anti-bacteria, anti-cancer, and liver protection. Leonurine, which is a major bioactive in , is known to possess biological effects including anti-inflammation, anti-fibrosis, anti-angiogenesis, and anti-diabetes. However, the preventive effects of and leonurine on muscle have not been reported. The current study aimed to determine the inhibitory effects of standardized extract (LJE) and leonurine on muscle atrophy by clarifying their underlying molecular mechanisms in tumor necrosis factor-alpha (TNF-α)-stimulated L6 myotubes. LJE and leonurine stimulated the phosphatidylinositol 3-kinase/Akt pathway that was reduced by TNF-α treatment. LJE and leonurine not only increased the mammalian target of rapamycin pathway for protein anabolism but also decreased the mRNA expression of E3 ubiquitin ligases by blocking the translocation of Forkhead box O, which is closely linked with proteolysis. Additionally, LJE and leonurine alleviated inflammatory responses by downregulating TNF-α and interleukin-6 mRNA expression and reducing the protein expression of nuclear factor-kappa B, a major transcriptional factor of proinflammatory cytokines. Collectively, LJE and leonurine have potential as therapeutic candidates for inhibiting the development of skeletal muscle atrophy by activating the PI3K/Akt pathway and reducing inflammatory responses.
肌肉萎缩是由于固定、衰老和几种慢性疾病导致的肌纤维数量和大小减少的特征。益母草，属于唇形科，在韩国、中国和日本被广泛用作传统药物。先前的研究报告表明，益母草具有多种生理活性，如抗菌、抗癌和保肝。众所周知，益母草中的主要生物活性成分益母草碱具有抗炎、抗纤维化、抗血管生成和抗糖尿病等生物学作用。然而，益母草和益母草碱对肌肉的预防作用尚未得到报道。本研究旨在通过阐明标准化益母草提取物（LJE）和益母草碱在肿瘤坏死因子-α（TNF-α）刺激的 L6 肌管中对肌肉萎缩的抑制作用的潜在分子机制，确定它们的作用。LJE 和益母草碱刺激了磷酸肌醇 3-激酶/ Akt 通路，而 TNF-α 处理会降低该通路。LJE 和益母草碱不仅增加了促进蛋白质合成的哺乳动物雷帕霉素靶蛋白通路，而且通过阻断与蛋白水解密切相关的叉头框 O 的易位，降低了 E3 泛素连接酶的 mRNA 表达。此外，LJE 和益母草碱通过下调 TNF-α 和白细胞介素-6 mRNA 表达以及降低核因子-κB 的蛋白表达，减轻了炎症反应，核因子-κB 是促炎细胞因子的主要转录因子。总之，LJE 和益母草碱通过激活 PI3K/Akt 通路和减轻炎症反应，具有抑制骨骼肌萎缩发展的治疗潜力。
