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.

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].…”

Unveiling the Potential of Nelumbo nucifera-Derived Liensinine to Target The Myostatin Protein and to Counteract Muscle Atrophy

“…It is a member of the transforming growth factor β (TGF-β) family and commonly referred to as growth differentiation factor 8 (GDF8), serving as a potent suppressor of muscle development. − Active MSTN can bind to the activin receptor type IIB (ActRIIB) on muscle cells to trigger downstream signaling and to exert inhibitory effects on muscles . Drugs that target MSTN have emerged as a promising therapeutic approach for the treatment of muscle atrophy. − However, no pharmaceuticals targeting this protein have been introduced into clinical practice. Natural compounds derived from food sources represent a treasure trove of nature; they contain numerous small molecules with unknown effects that hold great potential for pharmaceutical development. − While traditional screening methods are time-consuming and labor-intensive when it comes to screening a vast number of compounds, computer-aided drug design (CADD) can significantly shorten the time and process of drug screening.…”