Phytochemicals as neurotherapeutics in Alzheimer’s disease: Exploring plant-based interventions for emerging complex brain disorders

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and remains the most prevalent cause of dementia, accounting for approximately 60–70% of dementia cases worldwide and contributing substantially to disability and loss of independence in older adults. It is an increasing global health and economic burden. Its multifactorial, interconnected pathophysiology, including the deposition of amyloid-β (Aβ), hyperphosphorylation of tau, and neurofibrillary tangle (NFT) formation, as well as mitochondrial dysfunction and oxidative stress, makes treatment challenging because drugs targeting a single pathway often fail to cure or reverse the disease’s root cause. Conventional pharmaceutical therapies such as cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists offer only symptomatic relief with significant side effects. Hence, in this context, phytochemicals have emerged as promising neurotherapeutic candidates, due to their multi-target effects and reduced side effects. This review highlights key plant-derived bioactive compounds, including withanolides, curcumin, bacosides, epigallocatechin-3-gallate, resveratrol, rosmarinic acid, limonene, caffeic acid, and lycopene, and their proposed mechanisms relevant to AD prevention and management. Most studies on these bioactive compounds are preclinical. These phytochemicals have the potential to reduce Aβ plaque formation and tau pathology and to enhance antioxidant defense. Using nanotechnology approaches, their bioavailability can be improved. Therefore, by integrating traditional medicine knowledge with advanced molecular technologies, the phytochemical-based therapy can become a promising treatment for AD.