Translational potential of medicinal plants for Alzheimer’s disease: integrated evidence from molecular mechanisms to preclinical and clinical findings

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder driven by amyloid-β accumulation, tau hyperphosphorylation, oxidative stress, neuroinflammation, mitochondrial dysfunction, and cholinergic deficits. Despite extensive research, current FDA-approved therapies provide only modest symptomatic relief, underscoring the urgent need for safe and multi-targeted alternatives. This comprehensive review synthesizes evidence from in vitro, in vivo, and clinical studies on 15 medicinal plants and their 21 active compounds with therapeutic relevance to AD. Studies were included based on defined screening criteria: reported neuroprotective activity in at least one AD-related pathway, mechanistic evidence from preclinical or clinical investigations, and publication between 2015 and 2025. Analysis demonstrates that numerous plant extracts and isolated compounds including those from Allium sativum, Bacopa monnieri, Centella asiatica, Crocus sativus, Curcuma longa, Ginkgo biloba, Hericium erinaceus, Melissa officinalis, Nigella sativa, Salvia miltiorrhiza, Vitis vinifera, and others exert neuroprotective actions through convergent mechanisms. These include attenuation of oxidative and inflammatory pathways, inhibition of acetylcholinesterase and BACE-1, suppression of amyloid and tau pathology, enhancement of synaptic plasticity, mitochondrial support, and activation of neurotrophic signaling such as BDNF, TrkB and NRF2. Several compounds, including crocin, crocetin, curcumin, bilobalide, tanshinone IIA, bacosides, thymoquinone, and salvianolic acid B, demonstrate strong mechanistic activity across multiple AD-related pathways. Clinical trials further validate translational potential, with improvements reported in cognitive performance, behavioral symptoms, biomarker regulation, and daily functioning in individuals with mild cognitive impairment, AD, or age-related cognitive decline. Together, the evidence highlights medicinal plants as promising complementary or alternative strategies for modifying disease-relevant mechanisms and supporting cognitive health. Continued high-quality clinical investigations and optimized formulations are essential to advance these candidates toward therapeutic application.

Graphical abstract