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

Abstract

3-(4-Hydroxy-3-methoxyphenyl) propionic acid is an in vivo metabo­lite of 4-hydroxy-3-methoxycinnamic acid 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 3-(4-hydroxy-3-methoxyphenyl) propionic acid on muscle atrophy induced by dexamethasone was investigated using mouse C2C12 skeletal myotubes. Dexamethasone 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, along with their upstream regulator Krüppel-like factor 15. Dexamethasone dephosphorylated FoxO3a transcrip­tion factor and increased total FoxO3a expression. Interestingly, 10 ‍‍μM 3-(4-hydroxy-3-methoxyphenyl) propionic acid treatment significantly attenuated dexamethasone-induced reduction in myo­tube thickness and muscle protein degradation and suppressed muscle atrophy-associated ubiquitin ligases. 3-(4-Hydroxy-3-methoxyphenyl) propionic acid also prevented dexamethasone-induced Krüppel-like factor 15 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 3-(4-hydroxy-3-methoxyphenyl) propionic acid ameliorated glucocorticoid-induced muscle atrophy by suppressing Atrogin-1 and MuRF-1.