Abstract

AbstractBackgroundCognitive 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.MethodThirty‐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.ResultOur 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.ConclusionDiosmin reversed LPS‐induced cognitive impairment, which can be attributed to its neuroprotective and anti‐inflammatory properties.

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