Identification and Evaluation of Traditional Chinese Medicine Natural Compounds as Potential Myostatin Inhibitors: An In Silico Approach

Abstract

Myostatin (MSTN), a negative regulator of muscle mass, is reported to be increased in conditions linked with muscle atrophy, sarcopenia, and other muscle-related diseases. Most pharmacologic approaches that treat muscle disorders are ineffective, emphasizing the emergence of MSTN inhibition. In this study, we used computational screening to uncover natural small bioactive inhibitors from the Traditional Chinese Medicine database (~38,000 compounds) for the MSTN protein. Potential ligands were screened, based on binding affinity (150), physicochemical (53) and ADMET properties (17). We found two hits (ZINC85592908 and ZINC85511481) with high binding affinity and specificity, and their binding patterns with MSTN protein. In addition, molecular dynamic simulations were run on each complex to better understand the interaction mechanism of MSTN with the control (curcumin) and the hit compounds (ZINC85592908 and ZINC85511481). We determined that the hits bind to the active pocket site (Helix region) and trigger conformational changes in the MSTN protein. Since the stability of the ZINC85592908 compound was greater than the MSTN control, we believe that ZINC85592908 has therapeutic potential against the MSTN protein and may hinder downstream singling by inhibiting the MSTN protein and increasing myogenesis in the skeletal muscle tissues.

Current situation and publication trends of skeletal muscle related research: A bibliometric analysis

“…4 . Due to our interests in myogenesis, we explored the roles played by MSC activation, regeneration [ 10 ], extracellular matrix protein production [ 10 ], and natural compounds [ 20 , 21 , 32 ] in SM aging and related diseases. Our laboratory is devoted to the screening of natural compounds and designing peptides against selected targets responsible for SM degeneration.…”

A Prospective Case-Control Study Examining the Relationship Between Frailty and Serum Myostatin in Older Persons with Chronic Heart Failure

“…As a result, MSTN is a key therapeutic target. 25 ZINC85592908, according to Ali et al, 26 may prevent downstream signaling by blocking the MSTN protein and increasing myogenesis in skeletal muscle tissues. ZINC85592908 also has anti-MSTN protein therapeutic potential.…”

The roles of growth factors and hormones in the regulation of muscle satellite cells for cultured meat production

“…Cell culture experiments have also revealed that MSTN inhibits the proliferation and differentiation of cultured muscle cell lines and primary myogenic cells [93], which suggests siRNA1 and siRNA5 might reduce MSTN gene expression and boost sheep meat yield [94]. Some natural compounds [95][96][97] and inhibitory peptides targeting MSTN [21,98], such as Ac-MIF1 and Ac-MIF2-NH2, have been reported to inhibit the effect of MSTN significantly and enhance cell proliferation [99]. Additionally, in vivo and in vitro data showed that FMOD prevents muscle aging by decreasing the activity of MSTN protein [92].…”