Pharmacological modulation of intracellular signalling pathways involved in oxi-inflammageing and age-related cardiovascular pathologies by naturally occurring molecules

In the last decades, the average lifespan has progressively increased. Ageing dramatically predisposes to the onset of cardiovascular disorders (i.e. hypertension, ischemic stroke and heart failure), which still represent the leading cause of mortality worldwide. Therefore, the identification of novel pharmacological strategies for the prevention of cardiovascular ageing is a timely challenge. In this context, SIRT1 enzyme plays a crucial role, since it elegantly regulates downstream pathways involved in cell senescence, oxidative stress and inflammation. Interestingly, many naturally occurring compounds, including polyphenols, are SIRT1 activators. In the first part of this study, the anti-ageing effects of the Citrus flavonoid naringenin have been demonstrated in the myocardium of mice; moreover, the beneficial effects of a Citrus bergamia juice in the aged heart have been also investigated. Recently, it has been also proposed that the gasotransmitter hydrogen sulfide (H2S) is an endogenous activator of SIRT1 in the cardiovascular system. Hence, in the second part of this thesis the preventive effects of the H2S-donor Erucin (an isothiocyanate from Eruca sativa Mill.) against vascular inflammation, hypertension and myocardial ischemia/reperfusion injury have been demonstrated both in vitro and in vivo. Moreover, the beneficial effects of dietary intake of an extract of Eruca sativa Mill. (titled in the glucosinolate glucoerucin) have been investigated in a murine model of metabolic syndrome. Results showed that a pharmacological/nutraceutical approach with Citrus polyphenols and isothiocyanates from Brassicaceae may be useful in both the prevention and treatment of age-related cardiovascular diseases.