Re-emergence of medicinal plant materials rich in ellagitannins?

Ellagitannin-rich plant materials were for the long time beyond the mainstream of the natural product research. Despite many of them were used in Traditional European Medicine (TEM) and some have nowadays a monograph in European Pharmacopoeia, their phytochemical composition and biological activities were not an attractive scientific target. This was because ellagitannins (ETs) as high molecular weight polyphenols, were commonly considered to be difficult for isolation and structure elucidation, while their biological effects were attributed to unspecific protein binding properties.

Our studies were thus focused on so far underestimated ET-rich plant materials used in TEM for treatment of inflammation-associated diseases of i.a. skin, mucosa and gastrointestinal tract or as chemopreventive agents. During our investigations many ellagitannins were isolated. Complex comparative studies on human neutrophil ex vivo model have shown interesting differences in modulation of inflammatory response between extracts and isolated ellagitannins indicating also structure-dependent activities for single compounds. These results support the traditional use of chosen ET-rich plant materials, however due to doubtful bioavailability of ETs, they can only be referred to the topical application. In order to find out what could be the fate of ETs after oral administration, studies of extracts' and ETs' metabolism using human gut microbiota ex vivo cultures were conducted showing that they are transformed to the series of small-molecule, bioavailable compounds called urolithins. The urolithins were tested on various cellular models including neutrophils and macrophages. Obtained results have shown strong and specific inhibitory activities of urolithins towards various pro-inflammatory processes, which were observed at concentrations within their bioavailability.

The conducted investigations have proven, that the ET-rich plant materials used in TEM are attractive candidates for further research of novel anti-inflammatory and chemopreventive agents as well as indicated gut microbiota as a crucial factor determining their metabolism after oral administration.