Plant foods contain many physiologically active compounds, named polyphenols, that are produced in plants via secondary metabolism in relatively small amounts as a defence mechanism against predation, fungal, viral and microbial invasion, and UV irradiation. Epidemiological studies point to these substances as protective compounds active in the prevention of many degenerative diseases such as stroke, cardiovascular diseases, cancer and neurodegeneration. Polyphenols could be the key to alleviate neurodegeneration by acting as antioxidant, anti-inflammatory and immunomodulating compounds. Recent evidence indicates that nutraceuticals and whole diet approaches may protect against the development of age-related cognitive decline, such as Alzheimer¿s disease, and epidemiological studies suggest that a greater efficacy is attained when a mixture of polyphenols is administered rather than a single isolated compound, due to potential synergistic effects.
The aim of the present project is to isolate and characterize bioactive nutritional phytocomplexes of high impact on human health by using new green chemistry tools. Natural Deep Eutectic Solvents (NaDES) are emerging as powerful and biocompatible solvents to obtain ready to use, edible food supplements. They comprise a mixture of a hydrogen acceptor (e.g. choline, betaine) and a hydrogen bond donor (organic acids, polyalcohols, sugars) that results in a eutectic, i.e. a liquid that has a lower melting point than that of each individual component.
This project aims to:
- develop new NaDES suitable for human use which are non-toxic and have a negligible environmental impact
- extract polyphenols from various plant crop species and food products by the use of NaDES and to characterize them via spectroscopic and chromatographic methods
- test the extracts in in vitro and in vivo AD models for their: a) anti-inflammatory activity; b) antioxidant activity; c) neuroprotective activity
Plant extracts not only have the potential for multi-targeted effects, which are advantageous for complex diseases, but can also complement existing drug treatments for greater synergistic outcome. This project aims at obtaining polyphenol enriched extracts from edible plants by the use of new green solvents and at elucidating the biological effects of these extracts in in vitro and in vivo models of AD.
Disclosing the molecular mechanisms of polyphenol action may provide insights into disease pathway and contribute to identify new pharmacological targets and possible alternative therapeutic interventions in neurodegenerative diseases. This project involves different researchers whose scientific expertise spans from biochemistry and molecular biology, to analytical chemistry, and will exploit the expertise of external collaborators expert in plant physiology, biotechnology and genetics. They will cooperate to develop this project in a highly synergistic way, each providing their own specific sound competence, experience and capacity, and sharing a series of different techniques and experimental settings to obtain fully integrated information on the therapeutic potential of polyphenols in the treatment of AD. All the methods and techniques are already available and in current use. Thus, our project is truly translational: we will develop new products potentially useful in the nutritional treatment of neurodegenerative diseases and we will focus on basic mechanisms of neuroprotection in AD, translating this knowledge into new neuroprotective and potential restorative nutritional therapeutic approaches.
Furthermore, clarifying the effects of complex mixtures of polyphenols with possible synergistic activity may shed new light on the role of nutritional therapy in neurodegenerative disease. The detailed chromatographic characterization of the extracts will also allow a correlation with the biological activity in order to define a fingerprint of bioactive components in complex mixtures.
Disclosing the molecular mechanism of polyphenol action may also provide insights into disease pathway and contribute to identify new pharmacological targets and possible alternative therapeutic interventions.
The efficacy of the extracts will be assessed in different in vitro and in vivo models of AD, providing an integrated view or molecular and pathophysiological pathways involved in the disease onset/progression.
AD has a negative impact on the individual quality of life, limiting the ability of independent life. Due to increased life expectancy, AD incidence is increasing and is becoming a huge healthcare and social problem, since it drains considerable economic resources in Western Countries. In 2015, over 46 million people were living with dementia worldwide. This number is estimated to increase to 131.5 million by 2050 (World Alzheimer report, 2015). The possibility of slowing down, if not blocking at all, the progression of the disease with low-cost and easy-to-apply nutritional interventions would be able to bring great benefits not only to AD patients and their caregivers, but also to the field of social medicine, reducing the economic burden driven by the disease. The project has the potential to promote better health and quality of life and to reduce the high healthcare costs (over 80 billion per year) related to the treatment and care of elderly cognitively impaired patients. The potential gains in terms of number of lives and social expenditures saved are enormous.
We consider this project innovative because it will offer a new way of obtaining extracts enriched in antioxidants and neuroprotective substances, without the use of harmful organic solvents or other harsh systems. Furthermore, as the NaDES are composed of edible molecules, the extracts are ready-to-use, biocompatible and eco-friendly. The absence of any known toxicity of the principal constituents of NaDES (sugars, aminoacids, organic acids), which are normal components of food or arise from metabolic reactions in our body, makes these solvents extremely promising to the development of new food supplements/nutraceuticals enriched in protective substances.
Notably, the global polyphenols market is expected to substantially increase in the next future, with increasing consumer awareness of health benefits associated with their consumption, which are boosting the application of polyphenolic extracts in the food and beverages, pharmaceutical, and cosmetic industries. The food and agricultural product processing industries generate large amounts of phenolics-rich by-products, and this opens to the possibility of exploiting agrifood wastes as a renewable source of natural antioxidants, particularly in view of the possibility of extracting the active principles via biocompatible extraction solvents