Several experiments sustain healthful benefits of the
flavanone naringenin (Nar) against
chronic diseases including its protective effects against
estrogen-related
cancers. These experiments encourage Nar use in replacing
estrogen treatment in post-menopausal women avoiding the serious side effects ascribed to this
hormone. However, at the present, scarce data are available on the impact of Nar on E2-regulated cell functions. This study was aimed at determining the impact of Nar on the
estrogen receptor (ERα and β)-dependent signals important for 17β-estradiol (E2) effect in muscle cells (rat L6 myoblasts, mouse C2C12 myoblasts, and mouse skeletal muscle satellite cells). Dietary relevant concentration of Nar delays the appearance of skeletal muscle
differentiation markers (i.e., GLUT4 translocation,
myogenin, and both fetal and slow MHC
isoforms) and impairs E2 effects specifically hampering ERα ability to activate AKT. Intriguingly, Nar effects are specific for E2-initiating signals because
IGF-I-induced AKT activation, and myoblast
differentiation markers were not affected by Nar treatment. Only 7 days after Nar stimulation, early myoblast
differentiation markers (i.e.,
myogenin, and fetal MHC) start to be accumulated in myoblasts. On the other hand, Nar stimulation activates, via ERβ, the phosphorylation of
p38/MAPK involved in reducing the
reactive oxygen species formation in skeletal muscle cells. As a whole, data reported here strongly sustain that although Nar action mechanisms include the impairment of ERα signals which drive muscle cells to differentiation, the effects triggered by Nar in the presence of ERβ could balance this negative effect avoiding the toxic effects produced by oxidative stress .