The Polyherbal Wattana Formula Displays Anti-Amyloidogenic Properties by Increasing α-Secretase Activities.

Htut Htut Htoo,Jean-François Hernandez,Onusa Thamsermsang,Pravit Akarasereenont,Frédéric Checler,Narawut Pakaprot,Piyarat Govitrapong,Bruno Vincent,Suveerawan Limsuvan,Madepalli K Lakshmana

doi:10.1371/journal.pone.0170360

Abstract

Alzheimer’s disease is characterized by the deposition of insoluble amyloid-β peptides produced from the β-amyloid precursor protein (βAPP). Because α-secretase cleavage by ADAM10 and ADAM17 takes place in the middle of Aβ, its activation is considered as a promising anti-AD therapeutic track. Here we establish that the polyherbal Wattana formula (WNF) stimulates sAPPα production in cells of neuronal and non-neuronal origins through an increase of both ADAM10 and ADAM17 catalytic activities with no modification of BACE1 activity and expression. This effect is blocked by specific inhibition or genetic depletion of these disintegrins and we show that WNF up-regulates ADAM10 transcription and ADAM17 maturation. In addition, WNF reduces Aβ40 and Aβ42 generation in human cell lines. Altogether, WNF presents all the characteristics of a potent preventive anti-Alzheimer formula. Importantly, this natural recipe, currently prescribed to patients for the treatment of other symptoms without any secondary effect, can be tested immediately for further clinical studies.

Highlights

Alzheimer’s disease (AD) is a progressive and yet incurable neurodegenerative disorder affecting the elderly
We first evaluated the effect of Wattana formula (WNF) on the non-amyloidogenic α-secretase processing of β-amyloid precursor protein (βAPP) by cultured human HEK293 cells overexpressing βAPP751 and showed that concentrations from 1 up to 100μg/ml dose-dependently increase the secretion of sAPPα as well as the production of the α-secretase-derived C-terminal counterpart (C83 fragment) without modifying βAPP immunoreactivity (Fig 1A), thereby indicating that WNF most likely up-regulates the αsecretase processing of βAPP rather than βAPP expression
PDBu-stimulated (Fig 1C) WNF-dependent sAPPα secretion in βAPP-overexpressing HEK293 cells. Because these experiments were conducted in HEK293 cells artificially overexpressing high amounts of the βAPP protein, we wanted to determine whether WNF was able to generate similar effects in the same cell line producing endogenous levels of βAPP

Summary

Introduction

Alzheimer’s disease (AD) is a progressive and yet incurable neurodegenerative disorder affecting the elderly. Proteolysis of the β-amyloid precursor protein (βAPP) by enzymes called “secretase” is a central event since it determines both the production rate and the nature of the amyloid peptide (Aβ) [1], the main component of the extracellular senile

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