Cancer cachexia is a complex and multifactorial syndrome that influences about 50–80% of cancer patients and may lead to 20% of cancer deaths and muscle atrophy is the key characteristic of the syndrome. Recent researches have shown that myostatin is a negative regulator in the growth and differentiation of skeletal muscle. Herein, C2C12 cancer cachexia model was established with C26 conditioned culture medium (CCM), then treated with magnolol to evaluate the pharmacological activity of magnolol in myotube atrophy. Our results demonstrated that magnolol inhibited the activity of myostatin promotor and the myostatin signaling pathway. In C2C12 cancer cachexia model, magnolol decreased myostatin expression, inhibited the phosphorylation of SMAD2/3 activated by C26 conditioned culture medium (CCM), and elevated the phosphorylation of FOXO3a lowered by CCM. Myosin heavy chain (MyHC), myogenin (MyoG), and myogenic differentiation (MyoD), as three common myotube markers in C2C12 myotube, were decreased by CCM, which could be effectively reversed by magnolol via activation of AKT/mTOR-regulated protein synthesis and inhibition of ubiquitin-mediated proteolysis. This study reveals that magnolol inhibits myotube atrophy induced by CCM by increasing protein synthesis and decreasing ubiquitin-mediated proteolysis, so that magnolol is a promising leading compound in treating muscle atrophy induced by cancer cachexia.

中文翻译：

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厚朴酚在体外通过肌生成抑制素信号传导途径抑制癌症恶病质诱导的肌管萎缩。

癌症恶病质是一种复杂的多因素综合症，可影响约50-80％的癌症患者，并可能导致20％的癌症死亡，而肌肉萎缩是该综合症的关键特征。最近的研究表明，肌生长抑制素是骨骼肌生长和分化的负调节剂。在此，使用C26条件培养基（CCM）建立C2C12癌症恶病质模型，然后用厚朴酚处理以评估厚朴酚在肌管萎缩中的药理活性。我们的结果表明厚朴酚抑制了肌生长抑制素促进剂的活性和肌生长抑制素的信号传导途径。在C2C12癌症恶病质模型中，厚朴酚降低了肌肉生长抑制素的表达，抑制了由C26条件培养基（CCM）激活的SMAD2 / 3的磷酸化，并通过CCM降低了FOXO3a的磷酸化。肌球蛋白重链（MyHC），肌生成素（MyoG）和肌原性分化（MyoD）作为C2C12肌管中的三种常见肌管标志物，可通过CCM降低，而厚朴酚可通过激活AKT / mTOR调节蛋白合成有效逆转和抑制泛素介导的蛋白水解。这项研究表明厚朴酚通过增加蛋白质合成和减少泛素介导的蛋白水解作用来抑制CCM引起的肌管萎缩，因此厚朴酚是治疗癌症恶病质所致肌肉萎缩的有前途的领先化合物。厚朴酚可以通过激活AKT / mTOR调节的蛋白合成并抑制泛素介导的蛋白水解作用来有效逆转这种现象。这项研究表明厚朴酚通过增加蛋白质合成和减少泛素介导的蛋白水解作用来抑制CCM引起的肌管萎缩，因此厚朴酚是治疗癌症恶病质所致肌肉萎缩的有前途的领先化合物。厚朴酚可以通过激活AKT / mTOR调节的蛋白合成并抑制泛素介导的蛋白水解作用来有效逆转这种现象。这项研究表明厚朴酚通过增加蛋白质合成和减少泛素介导的蛋白水解作用抑制CCM引起的肌管萎缩，因此厚朴酚是治疗癌症恶病质所致肌肉萎缩的有前途的领先化合物。