To achieve this goal, a series of more than 30 plant species with potential healthy ageing effects was carefully selected from the Mediterranean diet as well as food plants from Africa, Asia and South America. The plants were collected, extracted and chemically characterized. Based on their chemical composition and literature data, the 10 most promising ones were selected and subjected to a comprehensive research platform including innovative cell, fly and mouse models for antioxidant effects and the development of age related diseases as well as metabolism assessment.
Specifically, a three-pronged approach to identify novel agents able to reduce ageing associated diseases and to improve health span was applied:
i) The 10 selected plant extracts were tested for potential health benefits in in vivo experiments in mice and flies. Mice were fed with extracts of the selected plants and markers for the development of age associated metabolic disorders such as diabetes type 2, dyslipidemia and cardiovascular diseases were analyzed. In addition, it was investigated if the plant extracts can protect the Drosophila flies from oxidative modifications.
ii) In parallel, the plant extracts were also forwarded to analysis in newly established cellular assays to determine their effects on the development of age related diseases (e.g. cellular diabetes models).
iii) In addition to the cell, fly and mouse models, the extracts were subjected to metabolization studies since plant extracts do not reach human tissues in their native form in most cases. In particular, biotransformation assays were applied to mimic the metabolism of compounds in the human body, including simulation of gastric and intestinal physiological conditions, microbial fermentation in the colon and enzymatic conversions in the liver.
Based on the results of these three parallel research lines, hit plants were selected for the phytochemical analysis and isolation of their bioactive chemical constituents. Advanced analytical techniques were used for the identification and characterization of the isolated natural products. Pharmacological profiling of bioactive natural products was carried out. The identified active molecules were also subjected to in silico methods to get better insight into possible mechanism of action. This was complemented by the synthesis of selected bioactive compounds and their derivatives to investigate qualitative and quantitative aspects of the observed bioactivity. Metabolomics approaches were applied to the hit extracts in order to identify the optimal sources for the procurement of the plants of interest.
Finally, the two most promising extracts (lead extracts) were selected and subjected to process optimization studies to proceed to the development of an innovative nutraceutical product. To achieve the optimal procedure for natural product procurement, optimization of extraction focusing on “green” extraction techniques and up-scaling procedures were applied. A pilot scale production of the lead extracts was developed and pre-formulation and stability studies were performed. Finally, to carry the lead extracts to the stage of development, feasibility studies were conducted.
This approach was unique and able to offer important and valuable results that facilitated and substantiated the development of an agent that is safe, characterized and exhibits specific biological activity against age related oxidative stress and metabolic disorders.
The results of the project were disseminated to other scientists outside the consortium and to the general public. In particular, scientific achievements of the project were disseminated to the scientific community through the presentation of the results at scientific meetings and the publication of articles in international scientific journals. Moreover, outreach activities such as workshops, a winter school and other special events were organized for the dissemination of the scientific information and for the benefit of public awareness.
