Neuroprotective effects of Elaeagnus glabra f. oxyphylla extract in amyloid-beta-induced cognitive deficit mice: Involvement of the PKC-delta, MYL2, and FER pathways.

Elaeagnus glabra f. oxyphylla (EGFO), a member of the Elaeagnaceae family, is an evergreen plant distinct from other species in its genus. We previously reported that ethanol extract from EGFO has memory improvement effects in a short-term memory deficit mouse model and anti-inflammatory effects in a microglial cell line. However, little is known about the pharmacological effects of EGFO. In the present study, we further explored the effect of EGFO on cognitive impairment using amyloid-beta-induced Alzheimer's disease (AD)-like mice. EGFO extract significantly enhanced cognitive functions in the passive avoidance task and Morris water maze test. EGFO treatment led to a significant increase in neuronal nuclei expression in mouse hippocampal tissues and inhibited hydrogen peroxide-induced cell death in HT22 hippocampal cells, indicating the neuroprotective effects of EGFO. Antibody microarray analysis was performed to determine the molecular mechanisms underlying the effects of EGFO on cognitive improvement and neuroprotection. The data revealed that EGFO decreased the phosphorylation of protein kinase C delta and increased the phosphorylation of myosin regulatory light chain 2 and tyrosine kinase Fer. These findings were validated using immunoblotting both in in vitro and in vivo AD models. Overall, our findings suggest that EGFO could be a candidate therapeutic agent for AD or AD-like diseases due to its potential for cognitive improvement and neuroprotection.