Proprietà protettive e antivirali dell'estratto di tegumento di mandorla in cellule U937: dalla riduzione dello stress ossidativo alla modulazione dell'infezione da parte di HSV-1.

Almond skin, rich in polyphenols, is increasingly studied for its antioxidant and antiviral properties. Recent research has highlighted its potential as a functional ingredient in healthrelated applications. The aim of this thesis was to evaluate the antioxidant and antiviral effects of almond skin extract (ASE) obtained from the Sicilian cultivar "Fascionello" and to investigate the underlying molecular mechanisms using an in vitro model of human monocytic U937 cells. In the first phase, in vitro studies confirmed the antioxidant properties of ASE. Data demonstrated that ASE pretreatment significantly inhibits intracellular ROS production and protects cells from apoptosis induced by oxidative stress. In a second experimental phase, three different storage conditions were tested to identify potential changes in the polyphenolic profile and antioxidant activity of almond skin over time. The goal was to establish an optimal storage protocol to preserve its bioactivity. Results showed that the antioxidant activity of ASE is retained when stored at 4°C in the dark for up to six months after harvesting, while other conditions led to a progressive decline in efficacy. Lastly, the antiviral effects of almond skin polyphenols were investigated as a function of dose and time to identify the phases and molecular mechanisms through which these compounds interfere with the herpes simplex virus type 1 (HSV-1) life cycle. The studies revealed that ASE pretreatment effectively inhibits HSV-1 replication in U937 cells by interfering with the viral entry phase. This likely involves modulation of the host cell receptor HVEM, critical for membrane fusion and viral penetration. In conclusion, the results of this thesis provide robust evidence supporting the antioxidant and antiviral properties of almond skin. When optimally stored to preserve its bioactive compounds, this by-product can serve as a valuable resource for pharmaceutical and nutraceutical applications. Moreover, valorizing Avola almond by-products promotes a circular economy model, facilitating optimal management of the agri-food industry waste and contributing to environmental sustainability.