Neurogenesis and neuroplasticity activities of natural products: therapeutic potential in Alzheimer’s disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, cognitive decline, and behavioral disturbance, largely associated with amyloid-β accumulation, tau protein pathology, synaptic dysfunction, oxidative stress and neuroinflammation. Previous research emphasizes the critical roles of impaired neurogenesis and neuroplasticity in cognitive dysfunction and neurodegenerative disorders, particularly AD. This review highlights the therapeutic potential of natural products in restoring these processes. It offers a comprehensive overview of the molecular mechanisms underlying neurogenesis and synaptic plasticity, with a focus on key regulatory pathways, such as BDNF/TrkB, ERK/CREB, PI3K/Akt and neurotransmitter signaling cascades. It also shows how the disruption of these regulatory pathways, caused by AD-associated pathological factors, results in reduced neuronal regeneration and synaptic connectivity. Furthermore, it summarizes preclinical data showing that various phytochemical compounds, such as ginsenosides, epigallocatechin gallate, curcumin, resveratrol, and flavonoids can improve neural stem cell proliferation, promote neuronal differentiation, and enhance synaptic function. Despite the promising pre-clinical studies results, clinical studies evaluating natural products remain limited due to poor bioavailability, inconsistent efficacy, and methodological constraints in human studies. To overcome these limitations, new strategies such as nanotechnology-based delivery systems and advanced brain targeting approaches are being developed. Overall, natural products represent promising candidates for managing neurogenesis and neuroplasticity in AD, although further clinical studies are required to validate their therapeutic efficacy.