Puerarin as a Modulator of Synaptic Plasticity: Molecular Mechanisms Underlying Learning and Memory Restoration in...

Neurodegenerative disorders (NDDs) are likely to become a major challenge for healthcare and society in the coming years, largely because of shifting global demographics. These conditions mainly involve the progressive deterioration or loss of neurons, which is a key factor behind serious mental health issues. Usually, NDDs are linked to a slow decline in neurons and their connections, often happening as people grow older. Synaptic dysfunction represents a fundamental pathological characteristic of these diseases and serves as a significant contributor to deficits in learning and memory. Puerarin, an isoflavonoid derived from Pueraria lobata, has surfaced as a promising neuroprotective compound with diverse molecular and cellular mechanisms of action. This review consolidates contemporary evidence regarding the function of puerarin as a modulator of synaptic plasticity and its therapeutic prospects in the restoration of cognitive function across various neurodegenerative conditions. We examine the manner in which puerarin impacts critical molecular pathways implicated in synaptic transmission and structural remodeling, encompassing the modulation of BDNF/TrkB signaling, the regulation of NMDA and AMPA receptor activity, the activation of CREB-dependent transcription, the enhancement of mitochondrial bioenergetics, and the mitigation of oxidative stress and neuroinflammation. Furthermore, we underscore its influence on dendritic spine density, long-term potentiation, and synaptic vesicle cycling, correlating these mechanisms with the observed enhancements in learning and memory in experimental models of Alzheimer's disease and Parkinson's disease. The review further explores the pharmacokinetic obstacles, methodologies for delivery, and translational viewpoints necessary to connect preclinical discoveries with clinical relevance.