title: Characterization of Pterocarpus erinaceus kino extract and its gamma-secretase inhibitory properties.
abstract: BACKGROUND
  The aqueous decoction of Pterocarpus erinaceus has been traditionally used in Benin against memory troubles.
  
  
  OBJECTIVE
  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 β-amyloid peptide (Aβ), whose accumulation and progressive deposition into amyloid plaques are key events in AD aetiology. Identifying new and more selective γ-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).
  
  
  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 Aβ release in both models. We further showed that KAST inhibited γ-secretase activity in cell-free and in vitro assays, strongly suggesting that KAST is a natural γ-secretase inhibitor. Importantly, this extract did not inhibit the cleavage of Notch, another γ-secretase substrate responsible for major detrimental side effects observed with γ-secretase inhibitors. Epicatechin was further identified in KAST by HPLC-MS.
  
  
  CONCLUSIONS
  Pterocarpus erinaceus kino extract appears therefore as a new γ-secretase inhibitor selective towards APP processing.
authors: Université catholique de Louvain, B-1200 Brussels, Belgium; Louvain Drug Research Institute (LDRI), Université catholique de Louvain, Belgium.
authors: Salim
authors: S
authors: Hage
authors: Université catholique de Louvain, B-1200 Brussels, Belgium; Institute of Neuroscience (IoNS), Université catholique de Louvain, Belgium.
authors: Serena
authors: S
authors: Stanga
authors: Université catholique de Louvain, B-1200 Brussels, Belgium; Institute of Neuroscience (IoNS), Université catholique de Louvain, Belgium.
authors: Claudia
authors: C
authors: Marinangeli
authors: Université catholique de Louvain, B-1200 Brussels, Belgium; Institute of Neuroscience (IoNS), Université catholique de Louvain, Belgium.
authors: Jean-Noël
authors: JN
authors: Octave
authors: Université catholique de Louvain, B-1200 Brussels, Belgium; Institute of Neuroscience (IoNS), Université catholique de Louvain, Belgium.
authors: Ilse
authors: I
authors: Dewachter
authors: Université catholique de Louvain, B-1200 Brussels, Belgium; Louvain Drug Research Institute (LDRI), Université catholique de Louvain, Belgium.
authors: Joëlle
authors: J
authors: Quetin-Leclercq
authors: Université catholique de Louvain, B-1200 Brussels, Belgium; Institute of Neuroscience (IoNS), Université catholique de Louvain, Belgium. Electronic address: pascal.kienlen-campard@uclouvain.be.
authors: Pascal
authors: P
authors: Kienlen-Campard
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology*; D053149:Plant Gums; D035721:Pterocarpus
chemical_list: D016229:Amyloid beta-Peptides; D010936:Plant Extracts; D053149:Plant Gums; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer׳s disease; Kino; Notch cleavage; Pterocarpus erinaceus; β-amyloid peptide; γ-secretase inhibitor