Bacopa monnieri and Alzheimer's disease: mechanistic convergence, cognitive outcomes and translational perspectives

Alzheimer's disease (AD), the leading cause of age-related cognitive decline and dementia, represents a growing neurological and socioeconomic burden, while currently approved therapies offer limited symptomatic benefit and minimal disease modification. Bacopa monnieri (L.) Wettst. (BM), a traditional Ayurvedic nootropic herb, has emerged as a promising phytotherapeutic candidate owing to its bioactive bacosides, which target multiple molecular pathways implicated in AD pathogenesis. This review, conducted following PRISMA 2020 principles, critically synthesizes evidence on the therapeutic relevance of BM in AD and cognitive decline. Literature from PubMed, Scopus, Web of Science and Cochrane Library was evaluated to examine phytochemistry, pharmacological mechanisms, preclinical and clinical evidence, cognitive outcomes, pharmacokinetics, safety, formulation strategies, comparative medicinal plant mechanisms and pharmacoeconomic positioning. Mechanistically, bacosides exert neuroprotective effects through cholinergic modulation, attenuation of amyloid-β accumulation, suppression of tau hyperphosphorylation via GSK-3β regulation, enhancement of brain-derived neurotrophic factor (BDNF)-mediated neuroplasticity and mitigation of oxidative stress and neuroinflammation through NF-κB signaling modulation. Preclinical findings consistently demonstrate improvements in cognition, synaptic plasticity and neuronal survival, whereas clinical studies using standardized extracts report favorable effects on memory, attention and processing speed with acceptable tolerability. Comparative analysis positions BM among promising neuroprotective medicinal plants for cognitive enhancement and supports its relevance to SDGs 3, 12 and 15. Nevertheless, variability in extract standardization, limited long-term clinical evidence and absent Alzheimer-specific pharmacoeconomic evaluations warrant biomarker-driven, large-scale randomized trials to clarify its therapeutic utility in AD.