Plant-derived phytochemicals for Alzheimer's disease: mechanisms of action, experimental evidence, and therapeutic perspectives.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by cholinergic deficits, amyloid-beta accumulation, tau hyperphosphorylation, oxidative stress, neuroinflammation, and synaptic dysfunction, which collectively contribute to cognitive decline and neuronal loss. Conventional pharmacotherapies provide symptomatic relief but largely target single pathological pathways, highlighting the need for multi-targeted approaches. Herbal therapeutics have emerged as promising complementary or alternative interventions, offering multifaceted mechanisms that simultaneously modulate key disease processes. Preclinical studies, including in vitro and animal models, indicate that extracts of medicinal plants, including Bacopa monnieri (aerial parts), Ginkgo biloba (leaves), Curcuma longa (rhizomes), and Withania somnifera (roots), may enhance cognitive function, exert neuroprotective effects, attenuate oxidative stress and inflammation, and modulate amyloid and tau pathology. However, clinical evidence remains limited, heterogeneous, and inconclusive, with existing studies reporting variable effects on memory, attention, executive function, and global cognition and generally providing only preliminary evidence of safety and efficacy. This translational gap is further influenced by poor bioavailability and brain delivery of several phytoconstituents, variability in herbal preparations, inadequate standardisation, differences in dosing and study design, and the scarcity of adequately powered, long-term clinical trials. Emerging approaches, including nanotechnology-based delivery systems, rational combinations with conventional therapeutics or complementary herbal agents, and personalised interventions based on genetic and metabolic characteristics, may improve therapeutic precision and clinical translation. Integrating mechanistic insights with experimental and clinical evidence may help identify the most promising herbal candidates while defining their translational limitations. This review synthesises current evidence and future directions, providing a framework for advancing herbal interventions in AD.