| Summary: | Abstract Paeonia ludlowii, a plant of the Paeoniaceae family, has abundant genetic diversity in different populations, and the seed oil can be used in a diverse number of activities. However, its neuroprotective effect is not clear. We investigated the memory‐improving effects and associated mechanisms of Paeonia ludlowii seed oil (PLSO) on amyloid beta (Aβ)25–35‐induced Alzheimer's disease (AD) in rats. The Morris water maze test was undertaken, and subsequently, the content of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and acetylcholinesterase (ACHE) in the hippocampus was detected by biochemical analyses. To further study PLSO, we examined the pathologic structure and apoptosis of hippocampal tissue by staining. Immunohistochemical analysis was used to detect expression of IBA‐1 and GFAP in the hippocampus. Detection of proinflammatory factors was achieved by reverse transcription–quantitative polymerase chain reaction and Western blotting. High‐dose PLSO inhibited expression of GFAP and IBA‐1. We demonstrated that high‐dose PLSO can regulate activation of glial cells and mediate apoptosis of hippocampal cells, and significantly improve learning and memory deficits in AD rats. PLSO could be developed as a nutritional supplement and sold as a drug for AD prevention and/or treatment.
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