Anthelmintic activity of procyanidins from West African medicinal plants – Insights into phytochemistry and molecular targets
24 October 2017 (online)
Oligomeric procyanidins (OPC) have been identified as the major anthelmintic components in hydroethanolic extracts from Combretum mucronatum leaves  and Paullinia pinnata roots  that are used as traditional remedies against soil-transmitted helminthiasis (STH) in West Africa . The traditional use was rationalized by in vitro mortality assays against Caenorhabditis elegans and selected parasitic helminths (Toxocara cati, Trichuris vulpis).
To investigate the anthelmintic activity of OPCs on a molecular level, a transcriptome analysis was performed in C. elegans after treatment with purified OPCs from C. mucronatum (0.02 to 2 mg/mL).
Highly significant changes in differential gene expression were observed mainly for proteins related to the intestine, many of which were located extracellularly or within cellular membranes. Among the up-regulated genes, several hitherto undescribed orthologues of structural proteins in humans were identified, but also genes that are potentially involved in the worms' mechanism of tannin detoxification. For example, T22D1.2, an orthologue of human Basic salivary proline-rich protein (PRB) 2 or a nuclear localized metal responsive (numr-1) were found to be strongly up-regulated. Down-regulated genes, were mainly associated with lysosomal activity, glycoside hydrolysis or the worms' innate immune response.
The current findings support previous hypotheses of OPCs interacting with intestinal surface proteins and provide the first insights into the nematode's response to OPCs on a molecular level as a base for the identification of future drug targets.
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