Attenuation of santonin in <i>β</i> -amyloid-induced Alzheimer’s disease via activation of ubiquitin-conjugating enzyme-2B in mice

Abstract Objectives Alzheimer’s disease (AD) is a chronic brain disorder. The progression of AD is known to cause irreversible neurodegeneration, and loss of neuronal density causes memory dysfunction. The administration of amyloid- β 1–42 (Aβ) oligomer causes AD in experimental animals. However, the role of santonin (ST) in the regulation of ubiquitin-conjugating enzyme E2B (UbcE2B) in AD conditions has not been reported yet. Hence, the present study was designed to investigate the role of ST against Aβ oligomer-induced AD in mice. Methods The AD in mice was induced by intracerebroventricular (i.c.v.) injection of Aβ oligomer (4 μg/4 μL) in mice. The test compounds, i.e., ST (30, 60, and 120 mg/kg of body weight) and donepezil (DP, 2 mg/kg), were administered orally (p.o.) for 21 consecutive days. The behavioral changes, i.e., the Morris water maze (MWM) test, Y-maze alternation test, and novel object recognition test (NORT), were assessed as per the experimental protocol. Furthermore, biomarkers, i.e., brain acetylcholinesterase (AChE) activity, thiobarbituric acid reactive substances (TBARS), catalase, and UbcE2B levels were estimated in mouse brain tissue samples. Besides, Aβ-associated brain histopathological changes were also evaluated by the eosin and hematoxylin staining method. Results The results revealed that ST attenuates the Aβ-induced changes in cognitive behaviors, biomarkers, and histopathological levels. Conclusions Hence, ST is considered a potential therapeutic agent for Aβ-associated AD progression. It may be due to its potential anti-oxidative, anti-inflammatory, and activation of UbcE2B activity. However, more extensive studies are required to prove this therapeutic potency in different AD conditions in various animal species.