Kim, June Hee Kim, Seong-Seop Lee, Elliot Hwejoon Oh, Soo-Jin Hong, Gyu-Sang Lee, Bonggi Cho, Ik-Hyun Choi, Chun Whan Kang, Taek Kim, Min Soo 2025-12-23T06:30:33Z 2025-12-23T06:30:33Z 2025-12-19 2025-12 0014-2999 https://pubs.kist.re.kr/handle/201004/153857 Dementia, a leading cause of disability affecting older adults worldwide, is characterized by memory and cognitive decline associated with dysregulated cholinergic activity and CREB–BDNF signaling. Polyphenols have been investigated for their potential to ameliorate these deficits. Gnetin H, a resveratrol derivative from Paeonia lactiflora seeds with known bioactive properties, has not been evaluated for neuroprotection. Here, we evaluated the neuroprotective actions of Gnetin H in a scopolamine-induced memory deficit model at cellular, slice, and animal levels. In SH-SY5Y neuroblastoma cells, Gnetin H (1 or 15 μM) promoted cell survival under scopolamine treatment. In hippocampal slices, acute bath application of Gnetin H (1.7 μM) enhanced long-term potentiation (LTP) despite scopolamine challenge, indicating preserved synaptic plasticity. In mice, central administration of Gnetin H (10 or 50 ng) restored memory performance in Y-maze, novel object recognition test, and Morris water maze, accompanied by recovery of cholinergic activity and CREB-BDNF signaling. Restoration of CREB-BDNF signaling was abolished by co-treatment of TrkB antagonist ANA-12 in SH-SY5Y cells, which confirmed involvement of TrkB-dependent CREB-BDNF signaling. Finally, Gnetin H rescued scopolamine-induced reductions in DCX-positive neurogenic cells and attenuated astrocytic (GFAP) and microglial (Iba1) reactivity in the hippocampus. In conclusion, Gnetin H exerts neuroprotective effects across cellular, slice, and animal models by enhancing synaptic plasticity (LTP) and restoring CREB-BDNF signaling through TrkB cascade, thereby supporting hippocampal neurogenesis and attenuating scopolamine-induced glial reactivity, with minimal effects under basal conditions. English Elsevier BV Neuroprotective effects of Gnetin H from Paeonia lactiflora via CREB-BDNF pathway restoration in a scopolamine-induced memory deficit model Article 10.1016/j.ejphar.2025.178363 1 European Journal of Pharmacology, v.1008 European Journal of Pharmacology 1008 N scie scopus 001620903200001 2-s2.0-105021812552 Pharmacology & Pharmacy Pharmacology & Pharmacy Article ALZHEIMERS-DISEASE RESVERATROL SEEDS SUFFRUTICOSA MAZE Paeonia lactiflora Gnetin H CREB BDNF LTP Neuroprotection Scopolamine