Effects of vanillic acid on Aβ1-40-induced oxidative stress and learning and memory deficit in male rats

Alzheimer’s disease (AD) is a neurodegenerative disease, in which the accumulation of β-amyloid (Aβ) peptide in
the extracellular space causes a progressive reduction in cognitive performance. Aβ stimulates active oxygen
species generation leading to oxidative stress and neural cell death. Vanillic Acid (VA) is the oxidant form of
vanillin widely found in vanilla beans. VA has many properties, such as suppressing apoptosis and eliminating
the harmful effects of oxidative stress in animal models. The VA effects on impaired learning and memory in Aβ
rats were assessed. Forty adults male Wistar rats were assigned to the following five groups in random: the
control, sham (received saline (vehicle) via intracerebroventricular (ICV) injection), Aβ (received Aβ1–40 via ICV
injection), VA (50 mg/kg by oral gavage once a day through four weeks), and Aβ + VA (50 mg/kg) groups. Open
field test, novel object recognition (NOR) test, Morris water maze (MWM) test, and passive avoidance learning
(PAL) task were performed, and finally, we determined the malondialdehyde (MDA), total antioxidant capacity
(TAC) and total oxidant status (TOS) levels. Aβ decreased the cognitive memory in NOR, spatial memory in
MWM, and passive avoidance memory in PAL tests. In contrast, VA improved learning and memory in the treated
group. Aβ significantly increased MDA and TOS and decreased TAC levels, whereas VA treatment significantly
reversed TAC, TOS and MDA levels. In conclusion, VA decreased the Aβ effects on learning and memory by
suppressing oxidative stress and can be regarded as a neuroprotective substance in AD.