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 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). 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 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. Conclusion Pterocarpus erinaceus kino extract appears therefore as a new γ-secretase inhibitor selective towards APP processing.

Characterization of Pterocarpus erinaceus kino extract and its gamma-secretase inhibitory properties

Stanga S.
Co-first
;
2015-01-01

Abstract

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 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). 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 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. Conclusion Pterocarpus erinaceus kino extract appears therefore as a new γ-secretase inhibitor selective towards APP processing.
2015
163
192
202
www.elsevier.com/locate/jethpharm
Alzheimer's disease; Kino; Notchcleavage; Pterocarpus erinaceus; β-amyloidpeptide; 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
Hage S.; Stanga S.; Marinangeli C.; Octave J.-N.; Dewachter I.; Quetin-Leclercq J.; Kienlen-Campard P.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1729474
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