{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:36:27Z","timestamp":1791513387244,"version":"4.3.4"},"reference-count":115,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD), the leading cause of dementia worldwide, is characterized by progressive neuronal loss, amyloid-\u03b2 (A\u03b2) aggregation, tau hyperphosphorylation, oxidative stress, neuroinflammation, cholinergic dysfunction, and gut\u2013brain axis dysregulation. Despite advances in anti-amyloid therapeutics, current interventions provide only modest symptomatic relief and face limitations in accessibility, cost, and long-term efficacy. Plant-derived bioactive compounds, rooted in traditional medicine systems such as Ayurveda and Traditional Chinese Medicine, have gained increasing attention as multi-target therapeutic agents due to their pleiotropic actions, relative safety, and ability to cross the blood\u2013brain barrier. This review synthesizes mechanistic and translational evidence on major phytochemicals, including withanolides (Withania somnifera), curcumin (Curcuma longa), ginkgolides and bilobalide (Ginkgo biloba), bacosides (Bacopa monnieri), ginsenosides (Panax ginseng), crocin\/safranal (Crocus sativus), epigallocatechin-3-gallate (Camellia sinensis), rosmarinic acid (Salvia officinalis, Melissa officinalis), and asiaticosides (Centella asiatica). These compounds exert neuroprotective effects by inhibiting A\u03b2 aggregation, reducing tau phosphorylation, scavenging reactive oxygen species, attenuating NF-\u03baB-mediated inflammation, modulating cholinergic signaling, enhancing synaptic plasticity via brain-derived neurotrophic factor\/cAMP response element-binding protein (BDNF\/CREB) activation, and regulating gut microbiota. Multi-target approach analyses underscore their synergistic potential in targeting interconnected AD pathways. However, translation remains hindered by poor oral bioavailability, rapid metabolism, and variability in clinical outcomes. Advances in delivery platforms, including liposomes, bilosomes, solid lipid nanoparticles, and nanostructured lipid carriers, are improving stability, blood\u2013brain penetration, and therapeutic efficacy in preclinical models. Collectively, plant-derived phytochemicals serve as promising, affordable, and multi-modal candidates for reshaping AD management, bridging traditional knowledge with modern therapeutic innovation.<\/jats:p>","DOI":"10.3390\/biom16010007","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T11:03:46Z","timestamp":1766142226000},"page":"7","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Advances in Bioactive Compounds from Plants and Their Applications in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"16","author":[{"given":"Steve","family":"Pavlov","sequence":"first","affiliation":[{"name":"USF Center for Microbiome Research, Microbiomes Institute, University of South Florida Morsani College of Medicine, Tampa, FL 33613, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0198-6863","authenticated-orcid":false,"given":"Santosh Kumar","family":"Prajapati","sequence":"additional","affiliation":[{"name":"USF Center for Microbiome Research, Microbiomes Institute, University of South Florida Morsani College of Medicine, Tampa, FL 33613, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4047-7236","authenticated-orcid":false,"given":"Dhananjay","family":"Yadav","sequence":"additional","affiliation":[{"name":"USF Center for Microbiome Research, Microbiomes Institute, University of South Florida Morsani College of Medicine, Tampa, FL 33613, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Marcano-Rodriguez","sequence":"additional","affiliation":[{"name":"USF Center for Microbiome Research, Microbiomes Institute, University of South Florida Morsani College of Medicine, Tampa, FL 33613, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4504-1597","authenticated-orcid":false,"given":"Hariom","family":"Yadav","sequence":"additional","affiliation":[{"name":"USF Center for Microbiome Research, Microbiomes Institute, University of South Florida Morsani College of Medicine, Tampa, FL 33613, USA"},{"name":"Center of Excellence in Aging and Brain Repair, Department of Neurosurgery, Brain and Spine, University of South Florida Morsani College of Medicine, Tampa, FL 33606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Jain","sequence":"additional","affiliation":[{"name":"USF Center for Microbiome Research, Microbiomes Institute, University of South Florida Morsani College of Medicine, Tampa, FL 33613, USA"},{"name":"Center of Excellence in Aging and Brain Repair, Department of Neurosurgery, Brain and Spine, University of South Florida Morsani College of Medicine, Tampa, FL 33606, USA"},{"name":"Department of Neurosurgery, Brain and Spine; Faculty of Center of Excellence for Aging and Brain Repair, University of South Florida, 12901 Bruce B Downs, MDC78, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"ref_1","unstructured":"Kumar, A., Sidhu, J., Lui, F., and Tsao, J.W. 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