Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a cascade of changes in cognitive, behavioral, and social activities. Several areas of the brain are involved in the regulation of memory. Of most importance are the amygdala and hippocampus. Antioxidant therapy is used for the palliative treatment of different degenerative diseases like diabetes, cirrhosis, and Parkinson’s, etc. The objective of this study was to assess the effectiveness of exogenous antioxidants, in particular, β carotene (1.02 and 2.05 mg/kg) against intracerebroventricular injected streptozotocin-induced memory impairment in mice. Streptozotocin (3 mg/kg, i.c.v) was administered in two separate doses (on 1st and 3rd days of treatment) for neurodegeneration. Fifty Albino mice (male) were selected in the protocol, and they were classified into five groups (Group I—control, Group II—disease, Group III—standard, Group IV–V—β-carotene-treated) to investigate the cognitive enhancement effect of selected antioxidants. The cognitive performance was observed following the elevated plus-maze, passive avoidance, and open field paradigms. Acetylcholine esterase, β-amyloid protein, and biochemical markers of oxidative stress such as glutathione peroxidase, superoxide dismutase, and catalase were analyzed in brain homogenates. In silico activity against acetylcholinesterase (AChE) was determined by the molecular modeling of β-carotene. β-carotene at a dose of 2.05 mg/kg was found to attenuate the deleterious effects of streptozotocin-induced behavioral and biochemical impairments, including the inhibition of acetylcholinesterase activity. The in silico studies confirmed the binding capacity of β-carotene with the acetylcholinesterase enzyme. The administration of β-carotene attenuated streptozotocin-induced cognitive deficit via its anti-oxidative effects, inhibition of acetylcholinesterase, and the reduction of amyloid β-protein fragments. These results suggest that β-carotene could be useful for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

Background and Objectives: Alzheimer’s disease (AD) is a neurodegenerative disorder that deteriorates daily life due to loss of memory and cognitive impairment. It is believed that oxidative stress and cholinergic deficit are the leading causes of AD. Disease-modifying therapies for the treatment of AD are a challenging task for this century. The search for natural and synthetic agents has attracted the attention of researchers. The objective of this study was a scientific approach to search for most suitable remedy for AD by exploiting the potential of Albizia lebbeck (L.) seeds. Materials and Methods: Hydromethanolic extract of Albizia lebbeck seeds (ALE) was prepared by maceration. The plant was characterized by physico-chemical, phyto-chemical, and high-performance liquid chromatography (HPLC). Thirty-six Wistar albino rats were used in this study and divided into six groups (n = 6). Group I: normal control; Group II: disease control (AlCl₃; 100 mg/kg); Group III: standard control (galantamine; 0.5 mg/kg); Groups IV–VI were treated ALE at 100, 200 and 300 mg/kg dose levels, respectively. All the treatments were given orally for 21 consecutive days. Y-maze, T-maze, Morris water maze, hole board, and open field behavioral tests were performed to analyze the cognitive impairment. Biochemical, histological, and computational studies were performed to support the results of behavioral tests. Results: HPLC analysis indicated the presence of quercetin, gallic acid, m-coumaric acid, and sinapic acid. ALE significantly improved the memory and cognitive impairments. Endogenous antioxidant stress biomarker levels and histopathological outcomes supported the therapeutic potential of A. lebbeck in AD. Cholinergic deficits were also ameliorated by ALE co-administration, possibly by the inhibition of hyperactive acetylcholinesterase (AChE). Docking studies supported the potential of ALE against AD. Conclusions: The data suggested that ALE has neuroprotective potential that can be exploited for beneficial effects to treat AD.