Abstract
Cholinergic dysfunction and impaired synaptic plasticity are key mechanisms underlying cognitive decline in neurodegenerative conditions, including Alzheimer's disease (AD). Schisandra chinensis pomace (SSP), a by-product of fruit processing, contains bioactive lignans and polyphenols with reported neuroprotective properties; however, its effects under cholinergic dysfunction have not been systematically investigated. In this study, the effects of SSP on scopolamine-induced cognitive impairment were evaluated using ex vivo electrophysiological and in vivo behavioral approaches. Multi-electrode array recordings demonstrated that SSP at 0.1 mg/mL significantly restored scopolamine-suppressed hippocampal long-term potentiation (LTP), whereas a higher concentration (1.0 mg/mL) did not restore hippocampal synaptic potentiation. In vivo, C57BL/6N mice received oral SSP (50 or 100 mg/kg/day) for six weeks, with scopolamine administered during the final three weeks. SSP at 50 mg/kg prevented scopolamine-induced body weight loss, attenuated hyperlocomotor activity, and significantly improved memory retention, as evidenced by enhanced performance in the passive avoidance and Morris water maze tests. Furthermore, SSP restored hippocampal brain-derived neurotrophic factor (BDNF) expression and reduced the p-JNK/JNK ratio, indicating modulation of neurotrophic and stress-responsive signaling pathways. Collectively, these findings suggest that SSP attenuates scopolamine-induced cholinergic dysfunction, accompanied by improved hippocampal synaptic plasticity and changes in BDNF and JNK signaling. These results support the potential of SSP as a neuroactive botanical resource under cholinergic challenge.