{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:47:42Z","timestamp":1782816462608,"version":"3.54.5"},"reference-count":48,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Government Research Training Program Scholarship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objective: Accumulation of amyloid-beta (A\u03b2) senile plaques in the human brain is a major hallmark of Alzheimer\u2019s disease (AD), which manifests as progressive decline in memory and cognitive functions and currently lacks effective disease-modifying therapies. Emerging evidence demonstrates that polyphenol-rich plant foods are potential complementary therapies for AD. Methods: In this study, we investigated crude polyphenol extracts (CPEs) and purified polyphenol extracts (PPEs) from three sorghum genotypes for their ability to inhibit A\u03b242-induced toxicity in MC-65 cells. Thioflavin T fluorescence, cell viability, mitochondrial function, oxidative stress assays, and Western blotting, along with RNA sequencing and computational analyses, were used to characterise both functional and transcriptomic responses of the cells to polyphenol treatments. Results: CPEs and PPEs inhibited A\u03b242 aggregation by 67\u201376% and significantly reduced A\u03b2 oligomer species. The extracts increased cell viability against A\u03b2-induced toxicity by more than 70%, decreased intracellular oxidative stress, and enhanced mitochondrial activity by over 80%. Transcriptomic profiling revealed differential modulation of genes associated with ferroptosis and MAPK\/NF- \u03baB signalling pathways, indicating regulation of inflammatory and oxidative-stress responses are mechanisms underlying the observed neuroprotection. Conclusions: This study demonstrates that polyphenol extracts from black and red sorghum genotypes exert strong multitarget neuroprotection against A\u03b242 toxicity in MC-65 cells. These findings support further evaluation of sorghum-derived polyphenols as complementary therapeutic candidates for AD, with in vivo studies required to establish efficacy and translational potential.<\/jats:p>","DOI":"10.3390\/nu18132121","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:01:17Z","timestamp":1782813677000},"page":"2121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Effects of Sorghum Polyphenol in Alzheimer\u2019s Disease: In Vitro and In Silico Analyses"],"prefix":"10.3390","volume":"18","author":[{"given":"Rasheed A.","family":"Abdulraheem","sequence":"first","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Joondalup, Perth, WA 6027, Australia"},{"name":"Alzheimer\u2019s Research Australia, Nedlands, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph N.","family":"Martins","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Joondalup, Perth, WA 6027, Australia"},{"name":"Alzheimer\u2019s Research Australia, Nedlands, Perth, WA 6009, Australia"},{"name":"Faculty of Medicine, Human and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia"},{"name":"Faculty of Health and Medical Sciences, The University of Western Australia, Crawley, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajapandiyan","family":"Krishnamoorthy","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, College of Food and Agriculture Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6358-0653","authenticated-orcid":false,"given":"Mohammad A.","family":"Alshuniaber","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, College of Food and Agriculture Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashant","family":"Bharadwaj","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Joondalup, Perth, WA 6027, Australia"},{"name":"Alzheimer\u2019s Research Australia, Nedlands, Perth, WA 6009, Australia"},{"name":"Faculty of Health and Medical Sciences, The University of Western Australia, Crawley, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5222-6832","authenticated-orcid":false,"given":"Zhaoyu","family":"Li","sequence":"additional","affiliation":[{"name":"Queensland Brain Institute, University of Queensland, St Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5261-1300","authenticated-orcid":false,"given":"Ranil","family":"Coorey","sequence":"additional","affiliation":[{"name":"School of Molecular and Life Sciences, Curtin University, Perth, WA 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Jayasena","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, Western Sydney University, Penrith, NSW 2751, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart K.","family":"Johnson","sequence":"additional","affiliation":[{"name":"School of Molecular and Life Sciences, Curtin University, Perth, WA 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.M.A.D. Binosha","family":"Fernando","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Joondalup, Perth, WA 6027, Australia"},{"name":"Alzheimer\u2019s Research Australia, Nedlands, Perth, WA 6009, Australia"},{"name":"Faculty of Health and Medical Sciences, The University of Western Australia, Crawley, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","first-page":"100154","article-title":"Natural acetylcholinesterase inhibitors: A multi-targeted therapeutic potential in Alzheimer\u2019s disease","volume":"11","author":"Gajendra","year":"2024","journal-title":"Eur. J. Med. Chem. 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