3-(4-Hydroxy-3-methoxyphenyl) propionic acid mitigates dexamethasone-induced muscle atrophy by attenuating Atrogin-1 and MuRF-1 expression in mouse C2C12 skeletal myotubes

3-(4-Hydroxy-3-methoxyphenyl) propionic acid (HMPA) is an in vivo metabolite of 4-hydroxy-3-methoxycinnamic acid (HMCA) which is abundantly found in coffee bean, rice bran, fruits, and vegetables. Previous studies reported that polyphenols and their metabolites exhibit positive effects on muscle health. Thus, the effect of HMPA on muscle atrophy induced by dexamethasone (Dex) was investigated using mouse C2C12 skeletal myotubes. Dex treatment (10 μM) reduced the diameter and myosin heavy chain protein expression in C2C12 myotubes; it also increased muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box protein 1/Atrogin-1 and muscle ring finger protein-1 (MuRF-1), along with their upstream regulator Krüppel-like factor 15 (KLF15). Dex dephosphorylated FoxO3a transcription factor and increased total FoxO3a expression. Interestingly, 10 μM HMPA treatment significantly attenuated Dex-induced reduction in myotube thickness and muscle protein degradation and suppressed muscle atrophy-associated ubiquitin ligases. HMPA also prevented Dex-induced KLF15 and FoxO3a expression. In conclusion, these results suggest that in vivo metabolite of polyphenols per se could be the real origin of the anti-muscular atrophy activity, as HMPA ameliorated glucocorticoid-induced muscle atrophy by suppressing Atrogin-1 and MuRF-1.