Piccolo, Vincenzo (2023) Identification and development of new nutraceuticals in support to the antiaging approaches. [Tesi di dottorato]

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Abstract

Aging is the progressive loss of body function over time, with a gradual decline of physical function of the organism. Recognizing aging as a significant risk factor for chronic diseases becomes crucial for the identification of new targets and the development of future therapeutic approaches. The aging process is associated with an increased susceptibility to some diseases, like Parkinson's and Alzheimer's diseases, metabolic syndrome, sarcopenia, and some skin diseases. The emerging role of the aging-related diseases represents a challenging for the national health system. Despite extensive studies on the pathophysiological mechanisms of aging, effective treatments remain ineffective. Today, the most effective approach is the prevention, mainly with dietary modifications and the physical exercise. Nutraceuticals could represent a valid strategy in aging-related diseases prevention for the health benefits related to the natural compounds of the food matrix. In this context, this thesis work is focused on the development of new nutraceutical formulations for the prevention of sarcopenia and the skin aging-relating diseases. In order to develop an innovative nutraceutical product for sarcopenia prevention, our resarch was focused on the identification of natural compounds active on the targets involved in muscle atrophy. These include the mammalian target of rapamycin complex 1 (mTORC1) and the Activating transcription factor 4 (ATF4). These mediators are modulated by tomatidine (TD), a natural alkaloid isolated from Solanum lycopersicum L. plant which represents the aglycone component of the glycoalkaloid α-tomatine (α-TM). Therefore, according to the aims of the doctoral project, I focused on the study of antisarcopenic properties of green tomatoes. In Chapter 3, the screening of 7 green tomato cultivars was performed to identify the food matrix with the higher α-TM content. The chemical composition and the evaluation of the antioxidant properties were assessed to evaluate the nutraceutical potential of the matrix. The matrix selection allowed to identify the “Datterini” tomatoes as the most promising tomato cultivar for further biological investigation. After that, in Chapter 4 the evaluation of the anti-sarcopenic properties of TD and the “Datterini” tomatoes was assessed. These results demonstrated the potential of this food matrix for the development of new nutraceutical for sarcopenia prevention. For the relevance of the tomato production in the Italian economy, and in particular in the Campania region (Southern Italy), an agronomic study was carried out and described in Chapter 5, investigating the chemical composition of a regional tomato variety called “Piennolo”. Agronomic parameters (e.g., harvest time), botanical parameters (e.g., anatomical part of tomato plant), and microbiological parameters (e.g., the treatment with beneficial microorganisms as Trichoderma spp.) were taken into account in this study. The research represented the most extensive metabolomic characterization of “Piennolo” tomato plant, providing interesting information on the Trichoderma spp. effects to influence metabolite production in tomato plant. In addition, a new food-grade approach to chemically convert α-TM to TD was investigated in Chapter 5, obtaining a new food matrix with a high TD content that could be employed for the development of an innovative nutraceutical for sarcopenia prevention. As second line of my thesis work, the development of an innovative cosmeceutical formulation for the prevention and the treatment of some skin aging-related diseases, as age spots, fine wrinkles, and hyperpigmentation, was performed. For this goal, we focused on ursolic acid, another natural compound of nutraceutical interest. Although this compound is present in several food matrices, the study was carried out using the apples of “Annurca” variety, typical of the Campania region in Southern Italy. In addition, to develop an ursolic acid enriched formulation for topical and cosmeceutical application, ursolic acid was delivered by the preparation of an oleolyte, an oil formulation obtained by maceration of the plant matrix in oil. In Chapter 6, an oleolyte obtained by the “Annurca” apples was developed and optimized using sunflower seed oil as oil vehicle. The oleolyte was chemically characterized for the evaluation of the qualitative and quantitative profile and the assessment of the antioxidant properties. After that, the skin-lighting properties of “Annurca” apple oleolyte and ursolic acid were evaluated in the Chapter 7. These results demonstrated the potential of this oleolyte for the development of new cosmeceutical formulations for the skin aging-related diseases prevention and treatment. Although my research work was focused on the development of new potential treatments for the prevention of aging-related diseases, during my Ph.D. thesis I work to other projects for the chemical analysis of other food matrices with a nutraceutical interest. In Chapter 8, I summarized the extraction contributions to other projects.

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