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

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 αsecretases 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.