Lindera glauca Blume ameliorates amyloid-β_1-42-induced memory impairment in mice with neuroprotection and activation of the CREB-BDNF pathway

Background: Alzheimer's disease (AD) is a neurodegenerative disorder presenting cognitive decline accompanied by deposits of amyloid-β (Aβ) and tau hyperphosphorylation. Without current treatment to AD, many studies suggested diverse approaches, one of which was herbal medicine and its active compounds. Very few studies have examined the effect of Lindera glauca Blume (L. glauca) in models of degenerative disease despite the attention that it received as a novel potential treatment source. We examined the efficacy of L. glauca in a mouse model of AD, which was induced by intrahippocampal injection of Aβ_1–42. Methods: Mice were intrahippocampally infused with Aβ_1–42 and were orally administered ethanolic extract of L.glauca before and after infusion for 21 days. Y-maze test and Morris water maze was conducted to assess memory impairment. Immunohistochemistry and western blot analysis were performed to assess the effect of L. glauca administration on pathological changes in mice. Results: L. glauca exhibited beneficial effects in spatial and reference learning as shown in increased time spent in the target quadrant in Morris water maze and increased spontaneous alternation in Y-maze. At the same time, decline of Aβ burden and phosphorylated tau were observed in the hippocampus of L. glauca-treated mouse under intrahippocampal injection of Aβ_1–42. The results corresponded with amelioration of the decreased neuronal marker, neuronal-specific nuclear protein (NeuN) and attenuation of the increased reactive astrocyte marker, glial fibrillary acidic protein (GFAP) levels in hippocampus. Additionally, 21-day treatment with L. glauca inhibited downregulation of phosphorylated cAMP response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) levels. Conclusion: L. glauca improves behavioral deficits induced by Aβ_1–42 and inhibits both Aβ- and tau-related pathological changes, stimulating neuroprotection mediated by CREB activation. L. glauca can be suggested as a new candidate for treatment of AD.