09:00 - 10:50
Room: The Chapel
Invited & Short Lecture
Chair/s:
Alvaro Viljoen, Zhi-Hong Jiang
Ellagitannins from Combretum aculeatum as possible effective prodrugs in TB treatment
ElHadji Assane Diop 1, 3, Emerson Ferreira Queiroz 1, Laurence Marcourt 1, Sebastien Kicka 2, Serge Rudaz 1, Tahir A. Diop 3, Thierry Soldati 2
1 School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva
2 Biochemistry department, Faculty of Science, University of Geneva, Geneva
3 Biology Department, University Cheikh Anta Diop, Dakar

Tuberculosis (TB), an infectious bacterial disease caused by Mycobacterium tuberculosis with extensive resistance against antibiotic . Using a stringent cell-based assay with Acanthamoeba castellani as host for the pathogen M. marinum , the extracts from an ethnopharmacologic survey were screened for antimycobacterial activity [Kicka &al PlosOne 2014] . Among the plants evaluated, the extract of Combretum aculeatum exhibited a relevant antimycobacterial activity [Diop E.A &al JEP 2017] . In order to identify the active principles, a bioassay-guided fractionation was undertaken using flash chromatography. The higher activities were linked to the fractions containing the anomers (α- and β) of the ellagitannin punicalagin (PNG) that were further purified. PNG have been reported to be responsible for various pharmacological activities, such as inhibition of carcinogenesis, host-mediated antitumor activities and antiviral activities. These PNG are however known to be extensively metabolized when ingested orally. E llagitannins hydrolysis yield ellagic acid, which is subsequently transformed by the human colon microflora into urolithins derivatives [Cerda,B &al J. Agr. Food. Chem 2003] .

To better document the possible anti-TB efficacy of C. aculeatum, the metabolites urolithin A, B and D were thus acquired and their antimycobacterial activity was assessed. Ellagic acid inhibited the growth of M. marinum in broth with an IC50 of 48.3 µg/ml. Urolithin D exhibited relevant anti-infective activities , with IC50 of 89.91 µg/ml. A quantification of PNG in the C. aculeatum preparation showed that its consumption at the usual doses may yield plasmatic levels of active metabolites in a concentration range similar to the IC50 determined in the in vitro assays. These results provide a rational for the use of this decoction for TB management.


Reference:
Session 2-2-SL-04:
Session:
Session 2-2:Biological and pharmacological activities of natural products
Presenter/s:
ElHadji Assane Diop
Presentation type:
Short lecture (oral presentation)
Room:
The Chapel
Chair/s:
Alvaro Viljoen, Zhi-Hong Jiang
Date:
Wednesday, 29th August, 2018
Time:
09:50 - 10:05
Session times:
09:00 - 10:50