Advances in Bioactive Compounds from Plants and Their Applications in Alzheimer’s Disease

Alzheimer's disease (AD), the leading cause of dementia worldwide, is characterized by progressive neuronal loss, amyloid-β (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, neuroinflammation, cholinergic dysfunction, and gut-brain 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-brain barrier. This review synthesizes mechanistic and translational evidence on major phytochemicals, including withanolides (<i>Withania somnifera</i>), curcumin (<i>Curcuma longa</i>), ginkgolides and bilobalide (<i>Ginkgo biloba</i>), bacosides (<i>Bacopa monnieri</i>), ginsenosides (<i>Panax ginseng</i>), crocin/safranal (<i>Crocus sativus</i>), epigallocatechin-3-gallate (<i>Camellia sinensis</i>), rosmarinic acid (<i>Salvia officinalis</i>, <i>Melissa officinalis</i>), and asiaticosides (<i>Centella asiatica</i>). These compounds exert neuroprotective effects by inhibiting Aβ aggregation, reducing tau phosphorylation, scavenging reactive oxygen species, attenuating NF-κB-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-brain 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.