Therapeutic potential of a Novel Peptide, Myoki, in Muscle Atrophy: Mechanisms and applications

Background/Objectives: With the rapidly aging global population, the incidence of sarcopenia is rising, making the development of effective prevention and treatment strategies critical. The present study aims to evaluate the effects and clinical efficacy of Myoki, a corn-derived peptide, using mouse-derived C2C12 myoblasts and an accelerated aging mouse model as well as a human clinical trial. Methods: In vitro, muscle atrophy was induced in C2C12 cells using 10 μM dexamethasone (DEX). Myoki was applied at concentrations up to 500 μM and its cytotoxicity was assessed via cell viability assays. Morphological changes were documented by microscopy, and the expression of muscle structural and differentiation proteins was measured using Western blot and qRT-PCR. The binding affinity between Myoki and myostatin was determined using surface plasmon resonance on a Biacore T200 system and validated by ELISA. For in vivo studies, 8-week-old male SAMP8 (accelerated aging) and SAMR1 mice were divided into three groups: SAMR1 control, SAMP8 negative control, and SAMP8 receiving Myoki. Muscle tissues were histologically examined to assess fiber density, thickness, and collagen deposition. In a clinical trial, 80 sarcopenic patients were randomly assigned to receive either Myoki combined with arginine and maltodextrin (100 mg) or the carrier alone for 12 weeks. Efficacy was evaluated by measuring muscle mass, 6‑meter walk test speed, hand grip strength, and serum levels of TNF‑α, estrogen, testosterone, IL‑6, IGF‑I, myoglobin, and AST. Results: Myoki showed no cytotoxicity up to 500 μM. In C2C12 cells, treatment with Myoki increased myofiber length in a dose- and time-dependent manner (up to 217.1%) and enhanced the expression of key muscle proteins (up to 818%). In the DEX-induced atrophy model, Myoki restored growth signaling and reduced expression of the atrophy markers MAFbx and MuRF1. SPR and ELISA confirmed a high binding affinity for myostatin. In SAMP8 mice, Myoki improved muscle fiber density and thickness while reducing collagen deposition. Clinically, patients treated with Myoki demonstrated significant improvements in muscle mass, walking speed, and hand grip strength, along with increased IGF‑I and myoglobin levels compared to controls. Conclusions: Myoki promotes myofiber growth and inhibits myostatin, suggesting its potential as a novel therapeutic approach for combating sarcopenia.