Beneficial Effects of Sideritis scardica and Cichorium spinosum against Amyloidogenic Pathway and Tau Misprocessing in Alzheimer’s Disease Neuronal Cell Culture Models

Article type: Research Article

Authors: Chalatsa, Ioanna^{a; 2} | Arvanitis, Demetrios A.^{b; 2} | Mikropoulou, Eleni V.^c | Giagini, Athina^a | Papadopoulou-Daifoti, Zeta^{d; 1} | Aligiannis, Nektarios^c | Halabalaki, Maria^c | Tsarbopoulos, Anthony^{d; e} | Skaltsounis, Leandros A.^c | Sanoudou, Despina^{a; b; *}

Affiliations: [a] 4th Department of Internal Medicine, Clinical Genomics and Pharmacogenomics Unit, Medical School, National and Kapodistrian University of Athens, Athens, Greece | [b] Molecular Biology Division, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece | [c] Department of Pharmacognosy and Natural Product Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece | [d] Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece | [e] Department of Bioanalytical, GAIA Research Center, The Goulandris Natural History Museum, Kifissia, Greece

Correspondence: [*] Correspondence to: Despina Sanoudou, PhD, FACMG, 4th Department of Internal Medicine, Clinical Genomics and Pharmacogenomics Unit, “Attikon” Hospital, Medical School, National and Kapodistrian University of Athens, Rimini 1, Chaidari 124-62, Greece. Tel.: +30 210 7462532; E-mail: [email protected].

Note: [1 ] This author passed away on March 17, 2016.

Note: [2 ] These authors contributed equally to this work.

Abstract: Background:Natural products are a significantly underutilized source of potential treatments against human disease. Alzheimer’s disease (AD) is a prime example of conditions that could be amenable to such treatments as suggested by recent findings. Objective:Aiming to identify novel potentially therapeutic approaches against AD, we assessed the effects of Cichorium spinosum and Sideritis scardica extracts, both distinct components of the Mediterranean diet. Methods/Results:After the detailed characterization of the extracts’ composition using LC-HRMS methods, they were evaluated on two AD neuronal cell culture models, namely the AβPP overexpressing SH-SY5Y-AβPP and the hyperphosphorylated tau expressing PC12-htau. Initially their effect on cell viability of SH-SY5Y and PC12 cells was examined, and subsequently their downstream effects on AβPP and tau processing pathways were investigated in the SH-SY5Y-AβPP and PC12-htau cells. We found that the S. scardica and C. spinosum extracts have similar effects on tau, as they both significantly decrease total tau, the activation of the GSK3β, ERK1 and/or ERK2 kinases of tau, as well as tau hyperphosphorylation. Furthermore, both extracts appear to promote AβPP processing through the alpha, non-amyloidogenic pathway, albeit through partly different mechanisms. Conclusions:These findings suggest that C. spinosum and S. scardica could have a notable potential in the prevention and/or treatment of AD, and merit further investigations at the in vivo level.

Keywords: Alzheimer’s disease, amyloid, amyloidosis, Cichorium spinosum , Mediterranean diet, mountain tea, neurodegenerative diseases, prevention, Sideritis scardica , tauopathies

DOI: 10.3233/JAD-170862

Journal: Journal of Alzheimer's Disease, vol. 64, no. 3, pp. 787-800, 2018