Myrcene (Myr) has been reported to show
neuroprotective effects in
cerebral ischemia. In this research work, we investigated the Myr effect on neurobehavioural, and neuropathological alteration in mice induced by
Aluminium trichloride (
AlCl3) and
D - galactose. The administration of
AlCl3 (5 mg/kg; p. o.), and
D - galactose (60 mg/kg; i. p.) for 90 days in mice resulted in spatial learning and
memory deficits,
cognitive decline, as well as neurotoxicity. The treatments with Myr low dose (100 mg/kg), Myr high dose (200 mg/kg),
donepezil (2 mg/kg), and Myr low dose + donepezil (100 + 2 mg/kg) were administered via intraperitoneal route for 30 days significantly reversed the neurobehavioral, and neuropathological effects of
AlCl3 and
D - galactose in mice. The results of behavioural tests such as Morris water maze, elevated plus maze, and locomotor; biochemical analysis such as
malondialdehyde (MDA),
glutathione (GSH),
superoxide dismutase (SOD),
catalase (CAT),
nitrite, and
acetylcholinesterase (AChE); and ELISA tests such as mouse β -
secretase (BACE),
amyloid-beta peptide1-42 (Aβ1 - 42),
tumor necrosis factor - α (TNF-α),
interleukin - 6 (IL-6), and
brain-derived neurotrophic factor (
BDNF) demonstrated a significant (p < 0.05)
neuroprotective effect of the Myr and
donepezil co-treatments. In addition,
hematoxylin and
eosin staining of the cerebral cortex and hippocampus revealed eosinophilic lesions and hyperchromatic nuclei in
Alzheimer's disease mice, but treatments with Myr low dose, Myr high dose,
donepezil, and Myr low dose + donepezil reversed these neurodegenerative effects. Myr showed these activities by enhancing synaptic plasticity and
cholinergic activity, as well as reducing oxidative damage,
neuroinflammation, Aβ1-42 aggregations, and histopathological damage. Myr alone and in combination with
donepezil may serve as a potential candidate for the treatment of
Alzheimer's disease.