Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea.
Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Korea.
Molecules. 2021 Sep 6;26(17):5407. doi: 10.3390/molecules26175407.
The skeletal muscle (SM) is the largest organ in the body and has tremendous regenerative power due to its myogenic stem cell population. Myostatin (MSTN), a protein produced by SM, is released into the bloodstream and is responsible for age-related reduced muscle fiber development. The objective of this study was to identify the natural compounds that inhibit MSTN with therapeutic potential for the management of age-related disorders, specifically muscle atrophy and sarcopenia. Sequential screening of 2000 natural compounds was performed, and dithymoquinone (DTQ) was found to inhibit MSTN with a binding free energy of -7.40 kcal/mol. Furthermore, the docking results showed that DTQ reduced the binding interaction between MSTN and its receptor, activin receptor type-2B (ActR2B). The global energy of MSTN-ActR2B was found to be reduced from -47.75 to -40.45 by DTQ. The stability of the DTQ-MSTN complex was subjected to a molecular dynamics analysis for up to 100 ns to check the stability of the complex using RMSD, RMSF, Rg, SASA, and H-bond number. The complex was found to be stable after 10 ns to the end of the simulation. These results suggest that DTQ blocks MSTN signaling through ActR2B and that it has potential use as a muscle growth-promoting agent during the aging process.
骨骼肌（SM）是人体最大的器官，由于其成肌干细胞群体，具有巨大的再生能力。肌肉生长抑制素（MSTN）是一种由 SM 产生的蛋白质，会释放到血液中，并负责与年龄相关的减少肌肉纤维发育。本研究的目的是确定具有治疗潜力的天然化合物，以抑制 MSTN，用于管理与年龄相关的疾病，特别是肌肉萎缩和肌肉减少症。对 2000 种天然化合物进行了连续筛选，发现二硫代对苯醌（DTQ）能以-7.40 kcal/mol 的结合自由能抑制 MSTN。此外，对接结果表明，DTQ 降低了 MSTN 与其受体激活素受体型-2B（ActR2B）之间的结合相互作用。通过 DTQ，MSTN-ActR2B 的整体能量从-47.75 降低到-40.45。对 DTQ-MSTN 复合物的稳定性进行了长达 100 ns 的分子动力学分析，以使用 RMSD、RMSF、Rg、SASA 和氢键数检查复合物的稳定性。复合物在 10 ns 后到模拟结束时保持稳定。这些结果表明，DTQ 通过 ActR2B 阻断 MSTN 信号，并且在衰老过程中作为促进肌肉生长的剂具有潜在用途。
