Antimycobacterial activity in a single-cell infection assay of ellagitannins from Combretum aculeatum and their bioavailable metabolites.

Authors:
Emerson Ferreira Queiroz
Emerson Ferreira Queiroz
University of Geneva
Switzerland
Laurence Marcourt
Laurence Marcourt
University of Lausanne
Switzerland
Serge Rudaz
Serge Rudaz
University of Geneva
Switzerland
Tahir Diop
Tahir Diop
University Cheikh Anta Diop
Dakar | Senegal
Thierry Soldati
Thierry Soldati
University of Geneva
Geneva | Switzerland
Jean-Luc Wolfender
Jean-Luc Wolfender
University of Geneva
Switzerland

J Ethnopharmacol 2019 Jun 23;238:111832. Epub 2019 Mar 23.

School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU - Rue Michel Servet 1, 1211, Geneva 11, Switzerland. Electronic address:

Ethnopharmacological Relevance: The water decoction of Combretum aculeatum aerial parts is traditionally used in Senegal to treat tuberculosis (TB). The extract shows significant antimycobacterial activity in a validated single-cell infection assay.

Aim Of The Study: The main aim of this study was to identify the antimycobacterial compounds in the water decoction of Combretum aculeatum. Since the traditional preparations are used orally, a bioactivity assessment of the possible bioavailable human metabolites was also performed.

Materials And Methods: The Combretum aculeatum water decoction extract was first fractionated by flash chromatography. The fractions were submitted to an antibiotic assay against Mycobacterium marinum and to a single-cell infection assay involving Acanthamoeba castellanii as a host. Using these approaches, it was possible to correlate the antimycobacterial activity with two zones of the chromatogram. In parallel with this liquid chromatography (LC)-based activity profiling, high-resolution mass spectrometry (UHPLC-HRMS/MS) revealed the presence of ellagitannin (Et) derivatives in the active zones of the chromatogram. Isolation of the active compounds was performed by preparative chromatography. The structures of the isolated compounds were elucidated by nuclear magnetic resonance (NMR). Additionally, the main human metabolites of commercially available Ets were biologically evaluated in a similar manner.

Results: The in vitro bioassay-guided isolation of the Combretum aculeatum water extract led to the identification of three Ets (1-3) and ellagic acid (4). The major compounds 2 and 3 (α- and β-punicalagin, respectively), exhibited anti-infective activity with an IC of 51.48 μM. In view of the documented intestinal metabolism of these compounds, some metabolites, namely, urolithin A (5), urolithin B (6) and urolithin D (7), were investigated for their antimycobacterial activity in the two assays. Urolithin D (7) exhibited the strongest anti-infective activity, with an IC of 345.50 μM, but this was moderate compared to the positive control rifampin (IC of 6.99 μM). The compounds assayed had no observable cytotoxicity towards the amoeba host cells at concentrations lower than 200 μg/mL.

Conclusion: The observed antimycobacterial properties of the traditional water decoction of Combretum aculeatum might be related to the activity of Ets derivatives (1-3) and their metabolites, such as ellagic acid (4) and urolithin D (7). Despite the relatively weak activity of these metabolites, the high consumption of tannins achieved by taking the usual traditional decoction doses should lead to an important increase in the plasmatic concentrations of these active and bioavailable metabolites. These results support to some extent the traditional use of Combretum aculeatum to treat tuberculosis.

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Source
https://linkinghub.elsevier.com/retrieve/pii/S03788741183363
Publisher Site
http://dx.doi.org/10.1016/j.jep.2019.111832DOI Listing
June 2019
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