Biofactories and prototypes for novel functional food, ingredients and bioactive compounds to combat malnutrition in aging and chronic diseases

Malnutrition is a common problem in the elderly and fragile population and has complex and multifactorial origin. Aging and chronic disease led to a progressive accumulation of oxidative damages that exacerbate aging and disease-related diseases, including immunosenescence. Antioxidant-rich foods are the most effective means of supporting endogenous antioxidant mechanisms, promoting cellular resilience, minimizing the harmful effects of reactive oxygen species, stimulating the immune system, and promoting resilience, health and longevity. Plant foods are a major part of the human diet. Besides major nutrients of protein and carbohydrate, plant foods also contain many secondary metabolites (SMs), such as polyphenols and flavonoids compounds with well-demonstrated antioxidant and anticancer activities. Polyphenols are currently considered the most promising antioxidants and anticancer agents for the development of supplements, ingredients, and nutraceuticals. Therefore, the main object of this proposal is the identification of plant supplements, ingredients, and nutraceuticals (e.g., astaxanthin, curcumin), and their incorporation of these value-adding traits in novel food. In particular in varieties of cereals enriched of phenolic compounds or plant cell cultures (PCCs) to increase the production of secondary metabolites and proteins that are of commercial interest as food ingredients to be used to alleviate non-communicable disease in humans.  In addition, plant-derived nanovescicles (PDNVs) will be developed as delivery system, loading high value ingredients. Finally, honeybee products that contain not fully characterized bioactive peptides such as propolis will be tested to investigate their biological activity.
 

1) ISB will perform an in vitro study to understand the immunoregulatory and anti- inflammatory mechanism that medicinal plant extracts - rich in polyphenols - may have on human cell cultures (Separation and culture of human monocyte-derived macrophages). 
2) IBBR will Identify the best plant materials for in vitro cell culture. It will be developing a metabolic engineering approach to produce specific metabolite/protein in PPCs and testing them as bioactive novel ingredient against non-communicable disease. 
3) IBBR will inoculate Mediterranean soft and durum wheat with endophytic bacteria having different plant growth promoting properties and analyse the phenotypic characteristics of the host plants and evaluate the changes in SMs production. 
4) IBBR will analyse and test anti- and pro-oxidant properties of pomace and leaf polyphenols extracts by chemical and electrochemical tests, and by biological assays on cancer cells.  
5) IBBR will develop PDNVs as a novel biotechnology solution to potentiality track different forms of malnutrition. 
6) IBBR will investigate the natural phytocannabinoids plant derived (β-caryophyllene and β-caryophyllene oxide) for their anticancer, analgesic, antioxidative anti-inflammatory properties. 
7) IPSP will sample propolis from honeybee colonies reared in isolated areas of the Campania Region. Peptide extraction and characterization by using liquid chromatography-mass spectrometry (LC-MS) will be performed to test the in vitro effects. 
8) ISA taking advantage of a formulation named Aliophen®, based on polyphenolic composition from barley malt, with beneficial effects against malnutrition in chronic and degenerative diseases, will develop a new prototype of ONS (Oral Nutritional Supplements) added with Aliophen® that will be tested on preclinical studies. 

1. Effective processes for preparation of polyphenol-rich extracts from medicinal plants belonging to local and/or foreign tradition able to reduce inflammation and regulate anti-inflammatory responses.

2. Reports on the generation of PCCs producing bioactive compounds and on the use of PCCs or their extract as novel functional food to test against non-communicable diseases due to malnutrition. 

3. Selection of endophytes that will colonize the host plants, positively influencing the production of SMs, which could help improve human malnutrition. 

4. Identification of phenolic complexes that can be co-administrated with clinically standardized therapies (preclinical evaluation) with dual activity, antioxidant and pro-oxidant, in the diet accompanying anticancer therapies. 

5. Development of a new green food supplement prototype based on active nutraceutical loaded PDNVs.

6. Assessment of the effectiveness of the analysis method that separates and quantifies β-caryophyllene in plant extracts and validate the method (GC-MS-MS). 

7. Pattern characterization of bioactive peptides from propolis and bee venom.

8. Multiple markers related to malnutrition-related conditions will be assessed following Aliophen® stimulation of selected in vitro models.