This study was conducted to assess the protective effect of walnut (Juglans regia L.) extract on
amyloid beta (Aβ)1-42-induced institute of
cancer research (ICR) mice. By conducting a Y-maze, passive avoidance, and Morris water maze tests with amyloidogenic mice, it was found that walnut extract ameliorated behavioral dysfunction and
memory deficit. The walnut extract showed a protective effect on the
antioxidant system and
cholinergic system by regulating
malondialdehyde (MDA) levels,
superoxide dismutase (SOD) contents,
reduced glutathione (GSH) contents,
acetylcholine (ACh) levels,
acetylcholinesterase (AChE) activity, and
protein expression of AChE and
choline acetyltransferase (ChAT). Furthermore, the walnut extract suppressed Aβ-induced abnormality of mitochondrial function by ameliorating
reactive oxygen species (ROS), mitochondrial membrane potential (
MMP), and
ATP contents. Finally, the walnut extract regulated the expression of zonula occludens-1 (ZO-1) and
occludin concerned with blood-brain barrier (BBB) function, expression of
tumor necrosis factor-alpha (TNF-α),
tumor necrosis factor receptor 1 (
TNFR1), phosphorylated
c-Jun N-terminal kinase (p-JNK), phosphorylated nuclear factor of kappa light
polypeptide gene enhancer in B-cells inhibitor (p-IκB),
cyclooxygenase-2 (COX-2), and
interleukin 1 beta (IL-1β), related to
neuroinflammation and the expression of phosphorylated
protein kinase B (p-Akt),
caspase-3, hyperphosphorylation of tau (p-tau), and
heme oxygenase-1 (HO-1), associated with the Aβ-related Akt pathway.