Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, 100 Chungparo 47-Gil, Yongsan-Gu, Seoul 04310, Korea.
The Graduate School of Biotechnology, Kyung Hee University, Yongin, Gyeonggi 17104, Korea.
Int J Mol Sci. 2017 Dec 18;18(12):2748. doi: 10.3390/ijms18122748.
Cachexia and sarcopenia are the main causes of muscle atrophy. These result in a reduction in the muscle fiber area, myo-protein content, and muscle strength, with various molecular modulators being involved. Although several reports have proposed potential therapeutic agents, no effective treatments have been found for muscle atrophy. We searched for myogenic modulators from medicinal plants to treat muscle diseases. We isolated six alkaloids from and evaluated their myogenic potential by using the MyoD reporter gene assay in C2C12 cells. Among the tested compounds, canadine showed the strongest transactivation of MyoD and increased MHC expression during myogenesis. The activation of p38 MAP kinase and Akt are major mechanisms that contribute to the myogenesis by canadine. Canadine increased the number of multinucleated and cylinder-shaped myotubes during myogenesis of C2C12 myoblasts. To determine the preventive effect of canadine in cancer-induced muscle wasting, differentiated C2C12 myotubes were treated with conditioned media from CT26 colon carcinoma culture (CT26 CM) in the presence of canadine. Canadine ameliorated the muscle protein degradation caused by CT26-CM by down-regulating the muscle specific-E3 ligases, MAFbx/atrogin-1 and MuRF1. In this study, we found that canadine from stimulates myogenesis and also inhibits muscle protein degradation. Therefore, we suggest canadine as a protective agent against muscle atrophy.
恶病质和肌肉减少症是肌肉萎缩的主要原因。这些会导致肌肉纤维面积、肌蛋白含量和肌肉力量减少，涉及各种分子调节剂。虽然有几项报告提出了潜在的治疗药物，但目前还没有发现治疗肌肉萎缩的有效方法。我们从药用植物中寻找肌生成调节剂来治疗肌肉疾病。我们从 中分离出六种生物碱，并通过 C2C12 细胞中的 MyoD 报告基因检测评估它们的肌生成潜力。在测试的化合物中，加拿大碱显示出最强的 MyoD 转录激活作用，并在肌生成过程中增加 MHC 的表达。p38 MAP 激酶和 Akt 的激活是加拿大碱促进肌生成的主要机制。加拿大碱在 C2C12 成肌细胞的肌生成过程中增加了多核和圆柱状肌管的数量。为了确定加拿大碱在癌症诱导的肌肉消耗中的预防作用，在存在加拿大碱的情况下，用 CT26 结肠癌细胞培养物的条件培养基（CT26 CM）处理分化的 C2C12 肌管。加拿大碱通过下调肌肉特异性 E3 连接酶 MAFbx/atrogin-1 和 MuRF1，减轻了 CT26-CM 引起的肌肉蛋白降解。在这项研究中，我们发现 中的加拿大碱刺激肌生成，同时抑制肌肉蛋白降解。因此，我们建议将加拿大碱作为预防肌肉萎缩的保护剂。
