{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T05:13:36Z","timestamp":1774674816122,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006952","name":"Louisiana Board of Regents","doi-asserted-by":"publisher","award":["LEQSF (2017-20)-RD-B-07"],"award-info":[{"award-number":["LEQSF (2017-20)-RD-B-07"]}],"id":[{"id":"10.13039\/100006952","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex progressive neurodegenerative disorder affecting humans mainly through the deposition of A\u03b2-amyloid (A\u03b2) fibrils and accumulation of neurofibrillary tangles in the brain. Currently available AD treatments only exhibit symptomatic relief but do not generally intervene with the amyloid and tau pathologies. The extra-virgin olive oil (EVOO) monophenolic secoiridoid S-(\u2013)-oleocanthal (OC) showed anti-inflammatory activity through COX system inhibition with potency comparable to the standard non-steroidal anti-inflammatory drug (NSAID) like ibuprofen. OC also showed positive in vitro, in vivo, and clinical therapeutic effects against cardiovascular diseases, many malignancies, and AD. Due to its pungent, astringent, and irritant taste, OC should be formulated in acceptable dosage form before its oral use as a potential nutraceutical. The objective of this study is to develop new OC oral formulations, assess whether they maintained OC activity on the attenuation of \u03b2-amyloid pathology in a 5xFAD mouse model upon 4-month oral dosing use. Exploration of potential OC formulations underlying molecular mechanism is also within this study scope. OC powder formulation (OC-PF) and OC-solid dispersion formulation with erythritol (OC-SD) were prepared and characterized using FT-IR spectroscopy, powder X-ray diffraction, and scanning electron microscopy (ScEM) analyses. Both formulations showed an improved OC dissolution profile. OC-PF and OC-SD improved memory deficits of 5xFAD mice in behavioral studies. OC-PF and OC-SD exhibited significant attenuation of the accumulation of A\u03b2 plaques and tau phosphorylation in the brain of 5xFAD female mice. Both formulations markedly suppressed C3AR1 (complement component 3a receptor 1) activity by targeting the downstream marker STAT3. Collectively, these results demonstrate the potential for the application of OC-PF as a prospective nutraceutical or dietary supplement to control the progression of amyloid pathogenesis associated with AD.<\/jats:p>","DOI":"10.3390\/nu13051702","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T06:01:33Z","timestamp":1621317693000},"page":"1702","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["(-)-Oleocanthal Nutraceuticals for Alzheimer\u2019s Disease Amyloid Pathology: Novel Oral Formulations, Therapeutic, and Molecular Insights in 5xFAD Transgenic Mice Model"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4717-1141","authenticated-orcid":false,"given":"Afsana","family":"Tajmim","sequence":"first","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Areli K.","family":"Cuevas-Ocampo","sequence":"additional","affiliation":[{"name":"Department of Pathology and Translational Pathobiology, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5424-9475","authenticated-orcid":false,"given":"Abu Bakar","family":"Siddique","sequence":"additional","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed H.","family":"Qusa","sequence":"additional","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy Ann","family":"King","sequence":"additional","affiliation":[{"name":"Department of Pathology and Translational Pathobiology, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaldoun S.","family":"Abdelwahed","sequence":"additional","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4481-3949","authenticated-orcid":false,"given":"Jafrin Jobayer","family":"Sonju","sequence":"additional","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1456-4064","authenticated-orcid":false,"given":"Khalid A.","family":"El Sayed","sequence":"additional","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,18]]},"reference":[{"key":"ref_1","unstructured":"Alzheimer\u2019s Association (2021, January 20). 2020 Alzheimer\u2019s Disease Facts and Figures. 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