             Send Orders for Reprints to reprints@benthamscience.net Current Medicinal Chemistry, 2022, 29, 2937-2950 2937 RESEARCH ARTICLE Molecular Effects of Pteryxin and Scopoletin in the 5xFAD Alzheimer’s Disease Mouse Model Irem Kiris 1 , Krystyna Skalicka-Wozniak 2 , Merve Karayel Basar 1 , Betul Sahin 3 , Busra Gurel 1 , Ahmet Tarik Baykal 1,3,* 1 Department of Medical Biochemistry, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey; 2 Independent Laboratory of Natural Products Chemistry, Medical University of Lublin, Lublin, Poland; 3 Acibadem Labmed Clinical Laboratories, R&D Center, Istanbul, Turkey Abstract: Background: Alzheimer’s disease (AD) is one of the most prevalent diseases with rapidly increasing numbers, but there is still no medication to treat or stop the dis- ease. Previous data on coumarins suggests that scopoletin may have potential benefits in AD. Objective: Evaluate the therapeutic potential of the coumarins with natural origin - sco- poletin and pteryxin- in a 5xFAD mouse model of AD Methods: Both compounds were administered at two doses to 12-month-old mice, which represent severe AD pathology. The effects of coumarins were assessed on cognition in mouse experiments. Changes in the overall brain proteome were evaluated using LC- MS/MS analyses. Results: The Morris water maze test implicated that a higher dose of pteryxin (16 mg/kg) significantly improved learning, and the proteome analysis showed pronounced changes of specific proteins upon pteryxin administration. The amyloid-β precursor protein, glial fibrillary acid protein, and apolipoprotein E protein which are highly associated with AD, were among the differentially expressed proteins at the higher dose of the pteryxin. Conclusion: Overall, pteryxin may be evaluated further as a disease-modifying agent in AD pathology in the late stages of AD. A R T I C L E H I S T O R Y Received: April 27, 2021 Revised: July 06, 2021 Accepted: July 11, 2021 DOI: 10.2174/0929867328666210827152914 Keywords: Alzheimer’s disease, 5xFAD, scopoletin, pteryxin, label-free proteomics, counter-current chromatog- raphy. 1. INTRODUCTION Alzheimer’s disease (AD) is a common neuro- degenerative disease with two major hallmarks: amy- loid-β (Aβ) plaques and neurofibrillary tangles (NFTs). Atrophy, neuroinflammation, and synaptic dysfunction have also been accepted as pathologic markers of AD. Clinical manifestations of AD, including memory loss, confusion with time and place, speaking and writing *Address correspondence to this author at the Department of Medi- cal Biochemistry, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey; Tel: +902165004828; Fax: +902165443940; E-mail: ahmet.baykal@acibadem.edu.tr problems, mood and personality changes, effectively interrupt daily activities, and eventually, patients be- come bedridden [1]. AD was the 5 th leading cause of death in 2016 and is currently considered a global epi- demic with 47 million patients worldwide and expected to reach 76 million in 2030 [2]. Along with the number of patients, the social and economic burden is increas- ing each year substantially. Even though FDA-approved few medications for symptomatic treatment, none of them can halt or re- verse progression [3, 4]. Therefore, there is an urgent need to find new therapeutic agents, and in this effort, numerous research is currently being performed using AD mouse models. 5xFAD mouse, which has five fa- - 3 /22 $65.00+.00 © 2022 Bentham Science Publishers