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Title: | Characterization of Pterocarpus erinaceus kino extract and its gamma-secretase inhibitory properties | Authors: | Hage, Salim Stanga, Serena Marinangeli, Claudia Octave, Jean-Noël DEWACHTER, Ilse Quetin-Leclercq, Joëlle Kienlen-Campard, Pascal |
Issue Date: | 2015 | Publisher: | ELSEVIER IRELAND LTD | Source: | JOURNAL OF ETHNOPHARMACOLOGY, 163 , p. 192-202 -202 | Abstract: | The aqueous decoction of Pterocarpus erinaceus has been traditionally used in Benin against memory troubles. Ethnopharmacological relevance: The aqueous decoction of Pterocarpus erinaceus has been traditionally used in Benin against memory troubles.Aim of the study: New strategies are needed against Alzheimer's disease (AD), for, to date, AD treatment is symptomatic and consists in drugs treating the cognitive decline. An interesting target is the beta-amyloid peptide (A beta), whose accumulation and progressive deposition into amyloid plaques are key events in AD aetiology.Identifying new and more selective gamma-secretase inhibitors or modulators (none of the existing has proven so far to be selective or fully efficient) appears in this respect of particular interest. We studied the activity and mechanisms of action of Pterocarpus erinaceus kino aqueous extract, after the removal of catechic tannins (KAST).Methods and results: We tested KAST at non-toxic concentrations on cells expressing the human Amyloid Precursor Protein (APP695), as well as on primary neurons. Pterocarpus erinaceus extract was found to inhibit A beta release in both models. We further showed that MAST inhibited gamma-secretase activity in cell-free and in vitro assays, strongly suggesting that MAST is a natural gamma-secretase inhibitor. Importantly, this extract did not inhibit the cleavage of Notch, another gamma-secretase substrate responsible for major detrimental side effects observed with gamma-secretase inhibitors. Epicatechin was further identified in MAST by HPLC-MS.Conclusion: Pteroanpus erinaceus kino extract appears therefore as a new gamma-secretase inhibitor selective towards APP processing. (C) 2015 Elsevier Ireland Ltd. All rights reserved. |
Keywords: | Alzheimer׳s disease;Kino;Notch cleavage;Pterocarpus erinaceus;β-amyloid peptide;γ-secretase inhibitor;Amyloid Precursor Protein Secretases;Amyloid beta-Peptides;Animals;CHO Cells;Cell Survival;Cells, Cultured;Cricetinae;Cricetulus;Mice;Neurons;Plant Bark;Plant Extracts;Plant Gums;Pterocarpus | Document URI: | http://hdl.handle.net/1942/30339 | ISSN: | 0378-8741 | e-ISSN: | 1872-7573 | DOI: | 10.1016/j.jep.2015.01.028 | ISI #: | 000351797300020 | Rights: | 2015 Elsevier Ireland Ltd. All rights reserved. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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