The exploitation of Mediterranean wild plants for pharmacological and nutraceutical purposes: traditional species for new health needs

Sclerophyllous evergreen shrubs are keystone components of Mediterranean ecosystems due to their specialized physiological and biochemical adaptations. These shrubs thrive in the challenging Mediterranean environment, which includes semi-arid and drought-prone areas, thanks to strong and resilient physiological and structural traits such as high water-use efficiency, drought-resilient leaves, and secondary metabolite modulation. These secondary metabolites, including phenolics and terpenoids, play a key role in ecological defence against pests, diseases, and abiotic stresses, while also offering potential human health benefits, including antioxidant, anti inflammatory, and antimicrobic properties. In this context, understanding Mediterranean species of pharmaceutical and nutraceutical interest becomes crucial and represents one of the prerequisites for their rational valorization and protection. Pistacia lentiscus L., an evergreen sclerophyllous shrub with a long ethnobotanical history, has recently been recognized from the European Medicine Agency for its mastic’s traditional use in gastrointestinal disorders and skin problems. However, the effects of abiotic stresses, particularly drought, on its secondary metabolite modulation remain poorly understood, and its fruits continue to be underutilized. In this context, research on P . lentiscus fruits offers valuable insights into how water stress affects plant biochemical and physiological responses, particularly the production of terpenes and phenolics. The fruits can be processed to produce an edible oil rich in terpenes and terpenoids, while the oil extraction process yields a by-product rich in phenolics. These bioactive compounds have disparate applications in nutraceuticals, dietary supplements, pharmaceuticals, and cosmetics. The aim of this PhD project was to investigate P . lentiscus fruits as a source of phytocomplexes for nutraceutical and health related applications. First, we planned the setting-up of a green extractive method, following circular economy principles, and scaling-up procedures to obtain a flavonoid-rich extract from P . lentiscus oilcake, an important by-product of the oil extraction process. Then, we conducted an in-pot experiment to investigate the modulation of terpenes and flavonoids in P . lentiscus fruits during ripening under a moderate deficit irrigation. Furthermore, in collaboration with Professor Anna Rita Bilia from the Department of Chemistry at the University of Florence, we developed and optimized a new microemulsion loaded with P. lentiscus fruits extract and utilizing its oil as a functional ingredient for oral administration. Lastly, in partnership with the Biology Department at the University of Minho (Braga, Portugal), we investigated the antioxidant activity of P. lentiscus fruit extracts and safety profile of the microemulsion. The study focused on a dual aspect: first, in vitro antioxidant assays (such as DPPH, ABTS, and SOD) were used to evaluate the extract’s ability to neutralize free radicals. Second, the microemulsion’s hepatic safety profile was assessed using Hep-G2 cell lines, with its antioxidant properties tested under oxidative stress conditions, induced by tert-butyl hydroperoxide (t-BHP). This research confirmed the strong antioxidant capacity of the extract and demonstrated the microemulsion's safety as a new drug delivery system for oral administration, suitable for nutraceutical applications. Overall, the results of this project highlight the potential of Pistacia lentiscus L., a resilient Mediterranean woody species, as a source of innovative therapeutic ingredients. The findings offer significant insights into its antioxidant properties, its application in nutraceutical formulation