Influence of chemical modifications of the urolithin A molecule on its metabolism and in vitro biological activity

Knowledge about the role of the gut microbiota in maintaining homeostasis in human organism has started to develop dynamically in recent years. Its activity is believed to be of key importance for health, especially through its influence on the immune system, nervous system and metabolism of nutrients and xenobiotics. Findings
concerning changes in the structure of orally ingested compounds under the influence of the intestinal microbiota caused that when assessing the effects of the substance on the human body
in food and medicine today, it is essential to include the activity of
biological metabolites formed in the intestine.
One of the groups of compounds that undergo significant structural changes under the influence of
intestinal microbiota are ellagotanoids, which are macromolecular polyphenols that
occur in many medicinal plant raw materials and are ingredients of food products
such as walnuts, almonds, pomegranate juice, raspberries, strawberries, or
wine maturing in oak barrels. It is known, however, that ellagotanoids do succumb
metabolism under the influence of the gut microbiota to urolithins, which, unlike
ellagotanoids are small molecule compounds with a well-established
bioavailability, which may reach high concentrations in blood, tissues, faeces and urine.
In vitro bioactivity studies performed with urolithines showed that
one metabolite in particular, namely urolithin A, exhibits strong anti-inflammatory properties. Despite very promising research results, it turned out that urolithin A
immediately after absorption in the intestine, is inactivated by human metabolism, so it can exhibit anti-inflammatory effects only locally in the intestine,
but not at the level of the whole organism.
The aim of the project is to carry out chemical modifications of urolithin A
leading to a molecule with similar anti-inflammatory activity, however
that is not rapidly metabolized in the body. Successful implementation of this complex
project will enable a closer look at the molecular mechanisms of anti-inflammatory activity of
urolithin A and will allow to indicate the structural elements of the molecule that determine the effect on the specific
biochemical pathways. The implementation of the project will lead to the selection of such structural modifications
that are stable, non-toxic, do not affect the activity, but at the same time
prevent rapid deactivation. In the longer term, the results obtained may constitute
a basis for the development of a new drug derived from the area of ​drugs of natural origin; the first drug based on post-biotic metabolites produced by the human intestinal microbiota.