Oleuropein aglycone induces autophagy in neonatal rat cardiomyocytes. Evidences of beneficial effects in an “in vitro” model of cardiomyopathy characterized by autophagy.

Several studies report that caloric restriction (CR) may be associated with the prolongation of life- and healthspan probably related to autophagy induction. Despite the beneficial effects of CR, this regime for long time is hard to be sustained. The discovery that polyphenols, natural compounds with recognized health benefits, could act as “CR mimetics” propose them as a viable therapeutic alternative in age-related diseases characterized by autophagy dysfunction(Alzheimer, Parkinson, cardiovascular diseases) . Our previous studies have highlighted the beneficial effects of oleuropein aglycone (OLE), phenol extract from olive oil, against Aβ deposition in vitro and in vivo. The protective effects were mainly related to a strong autophagy activation.The aim of the present study is investigating if OLE is able to induce autophagy in neonatal rat cardiomyocytes and to restore defective autophagy in cardiomyopathies. Neonatal rat cardiomyocytes exposed to 100 μM OLE showed increased autophagic vacuoles and an increase of autophagy-specific markers such as beclin1 and LC3II. Double immunofluorescence imaging of RFP-GFP-LC3 shows in addition an increase in autophagic flux after 6h of OLE treatment with autophagosome-lysosome fusion. Interestingly recent studies have shown that the alteration of autophagy-lysosome pathway is a major event in Heart Failure (HF). This condition appeared in part related to an increase of mitochondrial enzyme monoamine oxidase-A (MAO-A) activity that, during the metabolism of catecholamines, produces H2O2 that in turn disrupts autophagic flux leading to the accumulation of autophagosomes and cell death . On this line of research, our preliminary results show that OLE treatment counteracts the effects of MAO-A/H2O2 axis improving mitochondrial functionality and decreasing cell necrosis. Our project has also an industrial impact suggesting OLE as a nutraceutical compound that could be complemented with the traditional therapies of HF improving their effectiveness.