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Volume 50 Number 1
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Volume 49 Number 3

Research articles

ScienceAsia 49 (2023): 256-265 |doi: 10.2306/scienceasia1513-1874.2023.014

The standardized Centella asiatica extract ECa 233 regulates the catalytic activities of βAPP-cleaving secretases in human cell lines

Mehbuba Nur Prothaa,†, Therathep Srisutjarita,†, Arpita Deyb, Subhamita Maitrab,g, Jean-Francois Hernandezc, Mayuree H. Tantisirad, Yingrak Boondame , Narawut Pakaprota,*, Bruno Vincentb,f,*

ABSTRACT:      Alzheimer’s disease is a neurodegenerative disorder characterized by the accumulation of amyloid peptides in the brain. While the production of Aβ is dependent on the cleavage of the β-amyloid precursor protein by the β-secretase BACE1, the α-secretase activity, mainly supported by ADAM10, counterbalances this pathway by both preventing Aβ production and triggering the release of the neuroprotective soluble APP alpha (sAPPα metabolite. For this reason, strategies aimed at promoting α-secretase and/or blocking β-secretase seem to be indicated for the purpose of containing the disease. Here we investigated the effects of ECa 233, a standardized extract of the plant Centella asiatica, on βAPP levels and sAPPα secretion as well as on the expression and catalytic activity of the α-secretases ADAM10 and ADAM17 and the β-secretase BACE1 in human cells. Our results interestingly demonstrate that the ECa 233 extract is able to significantly stimulate α-secretase activity and to inhibit β-secretase activity in a dose-dependent manner in the human SH-SY5Y neuroblastoma cell line. In conclusion, these results reveal an original doubly beneficial effect of ECa 233, which is both capable of promoting the non-amyloidogenic α-secretase activity and interfering with the amyloidogenic pathway and thereby stands as a promising candidate for the future development of mild, safe and preventive therapeutic treatment of Alzheimer’s disease.

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a Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 Thailand
b Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170 Thailand
c Institut des Biomol?cules Max Mousseron, UMR5247 CNRS/Universit? de Montpellier/ENSCM, Facult? de Pharmacie, 34093 Montpellier Cedex 5, France
d Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131 Thailand
e Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok 10400 Thailand
f Centre National de la Recherche Scientifique, 2 rue Michel Ange, Paris 75016 France
g Department of Molecular Biology, Ume? University, Ume? 90736 Sweden

* Corresponding author, E-mail: narawut.pak@mahidol.ac.th, vincent@ipmc.cnrs.fr

Received 20 Jun 2022, Accepted 29 Oct 2022