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Background: Cognitive impairment is a major feature of many neurodegenerative disorders such as Alzheimer's disease, dementia etc. The progressive cognitive decline in Alzheimer's disease (AD) can be attributed to the fact that current anti‐Alzheimer's drug only treat AD symptoms without completely reversing cognitive impairment in AD patients. Therefore, it is imperative to develop new therapeutic remedies that can improve memory and ameliorate cognitive impairment in AD patients. Disomin is a flavone with antioxidant, anti‐inflammatory and anti‐apoptotic properties. This study evaluated the neuroprotective effects of diosmin on LPS‐induced cognitive impairment in mice. Method: Thirty‐six Swiss mice were randomly divided into six groups (n = 6). Group 1 received vehicle, group 2 received vehicle, groups 3 to 5 received diosmin (50, 100 and 200 mg/kg, p.o.) respectively group 6 received donepezil (50 mg/kg, p.o.). Sixty minutes after the treatment with the vehicle/Diosmin/Donepezil, lipopolysaccharide (LPS) (250ug/kg, i.p.) was administered daily to groups 2 to 6 for seven days. Twenty‐four hours after treatment on day 7, mice were subjected to Y‐maze test and the Novelty object recognition test (NORT) to assess their spatial and non‐spatial working memory. Subsequently, the mice were sacrificed and their brain samples were harvested for biochemical analysis (TNF‐alpha, Interferon gamma and interleukin‐12), immunohistochemical examinations (Amyloid beta, BDNF, IBA‐1, NLRP3 expression) and Golgi staining procedure for morphological alterations. Result: Our data shows that diosmin increased percentage alternation in Y‐maze test and discrimination ratio in NORT compared with the control group. Diosmin significantly (p<0.05) decreased TNF‐alpha, Interferon gamma and interleukin‐12 and reduced neurodegeneration in the CA1 region of the hippocampus & dendate gyrus when compared with the control group. Conclusion: Diosmin reversed LPS‐induced cognitive impairment, which can be attributed to its neuroprotective and anti‐inflammatory properties. [ABSTRACT FROM AUTHOR]

Background: Chronic neuroinflammation has become a cornerstone in the study of neurodegeneration and Alzheimer's diseases. Thymoquinone is a known anti‐inflammatory agent with a strong antioxidant activity. This study aimed at evaluating its mechanisms of neuroprotective effect against neurodegeneration, cognitive and synaptic dysfunctions in lipopolysaccharides‐induced Alzheimer‐like model in in mice. Methods: Following one‐week acclimatization, thirty‐five Swiss mice were distributed randomly into five groups (n = 7). Group I received vehicle (10mL/kg, p.o.), Group II (LPS) received vehicle (10mL/kg), Group III received TQ (15mg/kg), Group IV received TQ (30mg/kg, p.o) and Group V received donepezil (5mg/kg, p.o.) for seven days. Starting from day 8, sixty‐minutes after treatment with vehicle or TQ or donepezil, animals in groups II‐IV were daily injected with LPS (0.5mg/kg, i.p.) consecutively for seven days. Twenty‐four hours after the treatment on day fourteen of the study, Novel Object Recognition, (NORT), Y‐maze, were used to assess cognitive functions. Tumor necrosis factor‐α (TNF‐α), interlukin‐1β (IL‐1β), acetylcholinesterase (AChE) were assessed using ELISA techniques, microglia, amyloid‐beta, choline acetyltransferase (ChaT), synaptophysin, were quantified using immunohistochemistry, while, gene expression of interlukin‐10 and β‐secretase were measured with quantitative Polymerase Chain Reaction. Cox Golgi staining procedure was performed to evaluate morphology of the pyramidal dendrites. Results: LPS significantly impaired performance in the Y‐maze and NORT and induced behavioural abnormalities, compared to control. These were all ameliorated by treatment with TQ (15‐30mg/kg). The TQ also significantly (P<0.05) reduced the concentration of LPS‐induced TNF‐α, IL‐1β, AChE and expressions of amyloid‐beta, microglia and β‐secretase/mRNA in hippocampus and prefrontal cortex. The TQ increased IL‐10/mRNA, ChaT, synaptophysin in hippocampus and PFC. TQ significantly (P<0.05) prevented neurodegeneration of dendrite and neuronal cells in the hippocampus of LPS‐treated mice. Conclusion: Our study shows that thymoquinone possesses neuroprotective effect against LPS‐induced neurodegeneration and cognitive impairment by suppressing chronic neuroinflammation, cholinergic disruption, depleted synaptic protein and Aβ accumulation. [ABSTRACT FROM AUTHOR]