Bioassay-Guided Fractionation of a Leaf Extract from Combretum mucronatum with Anthelmintic Activity: Oligomeric Procyanidins as the Active Principle.

Verena Spiegler,Eva Liebau,Frank Petereit,Jandirk Sendker,Andreas Hensel

doi:10.3390/molecules200814810

Verena Spiegler, Eva Liebau + Show 3 more

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https://doi.org/10.3390/molecules200814810

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Journal: Molecules (Basel, Switzerland)	Publication Date: Aug 14, 2015
Citations: 83	License type: CC BY 4.0

Affiliation: University of Münster

Abstract

Combretum mucronatum Schumach. & Thonn. is a medicinal plant widely used in West African traditional medicine for wound healing and the treatment of helminth infections. The present study aimed at a phytochemical characterization of a hydroalcoholic leaf extract of this plant and the identification of the anthelmintic compounds by bioassay-guided fractionation. An EtOH-H2O (1:1) extract from defatted leaves was partitioned between EtOAc and H2O. Further fractionation was performed by fast centrifugal partition chromatography, RP18-MPLC and HPLC. Epicatechin (1), oligomeric proanthocyanidins (OPC) 2 to 10 (mainly procyanidins) and flavonoids 11 to 13 were identified as main components of the extract. The hydroalcoholic extract, fractions and purified compounds were tested in vitro for their anthelmintic activity using the model nematode Caenorhabditis elegans. The bioassay-guided fractionation led to the identification of OPCs as the active compounds with a dose-dependent anthelmintic activity ranging from 1 to 1000 μM. Using OPC-clusters with a defined degree of polymerization (DP) revealed that a DP ≥ 3 is necessary for an anthelmintic activity, whereas a DP > 4 does not lead to a further increased inhibitory effect against the helminths. In summary, the findings rationalize the traditional use of C. mucronatum and provide further insight into the anthelmintic activity of condensed tannins.

Highlights

1.5 billion people worldwide suffer from infestations with soil-transmitted helminths (STH) [1], with Ascaris lumbricoides, Trichuris trichiura and Ancylostoma duodenale being the most common parasites [2]
This study aims at gaining further insight into the phytochemical composition of a hydro-ethanolic leaf extract of C. mucronatum and at the identification of the active principles responsible for the anthelmintic activity by a bioassay-guided fractionation
We performed the fractionation by testing the anthelmintic activity after each separation step, but included the isolation and identification of inactive or less active compounds for an improved phytochemical characterization of the extract

Summary

Introduction

1.5 billion people worldwide suffer from infestations with soil-transmitted helminths (STH) [1], with Ascaris lumbricoides, Trichuris trichiura and Ancylostoma duodenale being the most common parasites [2]. Providing access to effective treatments is desirable for all people affected by these parasites, the long term efficacy remains undetermined and large-scale preventive actions bear the risk of resistances against the respective drugs to emerge [5,6,7]. This in turn will strongly limit the effective use of the very limited number of drugs against STH we are mainly relying on, namely albendazole, mebendazole, levamisole and pyrantel pamoate [8]. While at present the situation regarding resistances is not as severe as in veterinary medicine, monitoring of the drug efficacy should be improved and efforts in the development of new drugs be stepped up [9]

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