Mitochonic Acid 5 ameliorates skeletal muscle injury via suppression of TNF-α pathway

Skeletal muscle is an important organ and is essential for activities of daily living, sports, and locomotion. Muscle fiber injury is a common pathological condition among all age groups. It includes acute injuries caused by sports, and chronic damage that induces sarcopenia, especially in older people. Mitochonic Acid 5 (MA-5) is a newly synthesized indole acetic acid derivative, which improves the mitochondrial function through its interaction with mitofilin. To determine the effects of MA-5 on muscle damage and regeneration, we evaluated the impact of MA-5 on muscle injury induced by a cardiotoxin. We found that MA-5 treatment attenuated skeletal muscle injury through decreased inflammatory cell infiltration, and the promotion of early muscle regeneration and recovery of function. This was evidenced by increased grip strength and the cross-sectional area of regenerating fibers. Transcriptomic analysis revealed down-regulation of the TNF-α/NF-κB signaling pathway by MA-5 administration. Furthermore, MA-5 treatment increased the expression of key regenerative markers such as MyoD and Pax7. These findings highlight the therapeutic potential of MA-5 for managing muscle injuries and sarcopenia, by promoting efficient muscle recovery and modulating the inflammation.