The Ethyl Acetate Extract of Leaves of Ugni molinae Turcz. Improves Neuropathological Hallmarks of Alzheimer’s Disease in Female APPswe/PS1dE9 Mice Fed with a High Fat Diet

Article type: Research Article

Authors: Jara-Moreno, Daniela^{a; c; e; 1} | Castro-Torres, Rubn D.^{a; c; d; f; 1} | Ettcheto, Miren^{a; b; c; f} | Auladell, Carme^{d; f} | Kogan, Marcelo J.^e | Folch, Jaume^{b; c} | Verdaguer, Ester^{d; f} | Cano, Amanda^{c; g} | Busquets, Oriol^{a; b; c; f} | Delporte, Carla^{e; 2} | Camins, Antoni^{a; c; f; 2; *}

Affiliations: [a] Departament de Farmacologia, Toxicologia i Química Terapèutica, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, Barcelona, Spain | [b] Departament de Bioquímica i Biotecnologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Spain | [c] Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain | [d] Departament de Biologia Cellular, Fisiologia i Immunologia; Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain | [e] Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile | [f] Institut de Neurociències, Universitat Barcelona, Barcelona, Spain | [g] Departament de Farmàcia, Tecnologia Farmacèutica i Fisico-química, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, Barcelona, Spain

Correspondence: [*] Correspondence to: Antoni Camins PhD, Departament de Farmacologia, Toxicologia i Química Terapèutica, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, Avda/ Diagonal 643, E-08028 Barcelona, Spain. Tel.:+34 93 4024531; Fax:+34 934035982; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Note: [2] These authors contributed equally as senior authors.

Abstract: The most common type of dementia is Alzheimer’s disease (AD), a progressive neurodegenerative disease characterized by impairment in cognitive performance in aged individuals. Currently, there is no effective pharmacological treatment that cures the disease due to the lack of knowledge on the actual mechanisms involved in its pathogenesis. In the last decades, the amyloidogenic hypothesis has been the most studied theory trying to explain the origin of AD, yet it does not address all the concerns relating to its development. In the present study, a possible new preclinical treatment of AD was evaluated using the ethyl acetate extract (EAE) of leaves of Ugni molinae Turcz. (synonym Myrtus ugni Molina Family Myrtacea). The effects were assessed on female transgenic mice from a preclinical model of familial AD (APPswe/PS1dE9) combined with a high fat diet. This preclinical model was selected due to the already available experimental and observational data proving the relationship between obesity, gender, metabolic stress, and cognitive dysfunction; related to characteristics of sporadic AD. According to chemical analyses, EAE would contain polyphenols such as tannins, flavonoid derivatives, and phenolic acids, as well as pentacyclic triterpenoids that exhibit neuroprotective, anti-inflammatory, and antioxidant effects. In addition, the treatment evidenced its capacity to prevent deterioration of memory capacity and reduction of progression speed of AD neuropathology.

Keywords: APPswe/PS1dE9, ethyl acetate extract, high fat diet, hippocampus, neuroinflammation, Ugni molinae

DOI: 10.3233/JAD-180174

Journal: Journal of Alzheimer's Disease, vol. 66, no. 3, pp. 1175-1191, 2018