The current study elucidates pharmacological evaluation of
bromelain as a bioactive compound obtain from pineapple stem belongs to family Bromeliaceae in
AlCl3 and
D - galactose induced mice. In mice, co-administration of
AlCl3 at dose 5 mg/kg b.w., via the oral route, and
D - galactose at dose 60 mg/kg b.w., via intraperitoneal route for 90 days resulted in
cognitive impairment, spatial learning, and
memory deficits, as well as neurotoxicity. However, 30 consecutive days, treatments via an intraperitoneal route with
bromelain low dose (Brm L) at dose 10 mg/kg b.w.,
bromelain high dose (Brm H) at dose 20 mg/kg b.w.,
donepezil (Dnpz) at dose 2 mg/kg b.w., and Brm L + Dnpz at doses 10, 2 mg/kg b.w. were considerably reversed the effect of
AlCl3 and
D - galactose induced AD mice. Consequences of behavioral parameters (Morris water maze, elevated plus maze and locomotor), biochemical estimation (MDA, GSH, SOD, CAT,
Nitrite and AChE), and ELISA tests (mouse BACE, Aβ1 - 42, TNF-α, IL-6, and
BDNF) confirmed significant (p < 0.05)
neuroprotective effect of treatments in
AlCl3 and
D - galactose induced mice. Additionally,
hematoxylin and
eosin staining of the cerebral cortex and the hippocampus exposed eosinophilic lesions and hyperchromatic nuclei in AD mice, but these neurodegenerative effects were eliminated by Brm L, Brm H, Dnpz, and Brm L + Dnpz treatments. Thus,
bromelain alone and in combination with
donepezil prevent
AlCl3 and
D - galactose induced spatial learning and
memory deficits, as well as
cognitive impairment, by increasing
cholinergic activity and synaptic plasticity, as well as reducing oxidative damage,
neuroinflammation, Aβ 1-42 aggregations, and histopathological damage, according to our findings. The present study consequences indicate that
bromelain alone and in combination with
donepezil appears to have neuroprotective properties. Henceforward, this may be a promising treatment option for
Alzheimer's disease.