Neuroprotective effect of alpha‐pinene is mediated by suppression of the TNF‐α/NF‐κB pathway in Alzheimer's disease rat model

Monoterpene alpha-pinene possesses antioxidant, cardioprotective, and neuroprotective properties. We evaluated the effect of alpha-pinene on oxidative/nitrosative stress, neuroinflammation, and molecular and behavioral changes induced by beta-amyloid (Aβ)1-42 in rats and investigated the possible mechanisms of these outcomes. Male Wistar rats received alpha-pinene (50 mg/kg intraperitoneally) for 14 consecutive days after intrahippocampal injection of Aβ1-42 . Alpha-pinene decreased malondialdehyde and nitric oxide levels, increased glutathione content, and enhanced catalase activity in Aβ-injected rats. Also, messenger RNA expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, nuclear factor κB, and N-methyl- d-aspartate receptor subunits 2A and 2B reduced in the hippocampus of these animals. Besides this, alpha-pinene repressed the Aβ1-42 -induced reduction of nicotinic acetylcholine receptor α7 subunit and brain-derived neurotrophic factor expression. Treatment with alpha-pinene caused Aβ-receiving rats to spend more time in the target quadrant in the Morris water maze test and led to an increase in percentages of open arm entrance and time spent in the open arm in the elevated plus-maze test. We concluded that alpha-pinene strengthens the antioxidant system and prevents neuroinflammation in the hippocampus of rats receiving Aβ. It improves spatial learning and memory and reduces anxiety-like behavior in these animals. Consequently, alpha-pinene alleviates Aβ-induced oxidative/nitrosative stress, neuroinflammation, and behavioral deficits. It is probably a suitable candidate for the treatment of neurodegenerative diseases.