Standardized Hericium erinaceus Extract Powder Improves Scopolamine-Induced Cognitive Deficits via BDNF-Mediated Neuroplasticity

Alzheimer’s disease and related neurodegenerative disorders are associated with progressive cognitive decline, primarily driven by cholinergic dysfunction and impaired synaptic signaling. Hericium erinaceus, also known as lion’s mane mushroom, has been reported to promote neuronal differentiation and synaptic plasticity. In this study, a standardized H. erinaceus extract powder (HEP) was prepared from fruiting bodies and quantified using hericene A as a marker compound. The neuroprotective effects of HEP were then evaluated in both cellular and animal models of scopolamine-induced cognitive dysfunction. Pretreatment of SH-SY5Y human neuroblastoma cells with HEP (5–25 μg/mL) significantly improved cell viability and reduced scopolamine-induced apoptosis, while enhancing the activation of neuroplasticity-related signaling proteins, including brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and extracellular signal-regulated kinase (ERK). In vivo, oral administration of HEP (300 mg/kg) to scopolamine-treated ICR mice markedly improved cognitive performance, increasing the recognition index to 63.8% compared with 41.6% in the scopolamine group, and enhancing spontaneous alternation in the Y-maze test to 59.6%. These cognitive improvements were accompanied by preserved hippocampal neuronal structure and increased BDNF immunoreactivity. Additionally, HEP improved cholinergic function by restoring serum acetylcholine levels and reducing acetylcholinesterase activity. Collectively, these findings suggest that standardized HEP exerts neuroprotective and cognition-enhancing effects via modulation of cholinergic markers and activation of BDNF-mediated neuroplasticity, highlighting its potential as a functional food ingredient or nutraceutical for preventing cognitive decline related to cholinergic dysfunction.