Imperatorin ameliorates lipopolysaccharide induced memory deficit by mitigating proinflammatory cytokines, oxidative stress and modulating brain-derived neurotropic factor. (October 2018)

• Record Type: Journal Article
• Authors: Chowdhury, Amrita A.; Gawali, Nitin B.; Shinde, Prashant; Munshi, Renuka; Juvekar, Archana R.
• Is Part Of: Cytokine. Volume 110(2018)
• Page Start: 78
• Page End: 86
• Publication Date: 2018-10
• Subjects: Aβ amyloid beta -- AChE acetyl cholinesterase -- AD Alzheimer's disease -- ANOVA analysis of variance -- BSA Bovine serum albumin -- BDNF brain derived neurotrophic factor -- CPCSEA Committee for the Purpose of Control and Supervision of Experiments on Animals -- CNS central nervous system -- DNP donepezil -- LPS lipopolysaccharide -- GSH reduced glutathione -- IL-6 interleukin-6 -- IL-10 interleukin-10 -- IMP imperatorin -- MDA malonaldehyde -- MWM morris water maze -- NADPH nicotinamide adenine dinucleotide phosphate oxidase -- NFTs neurofibrillary tangles -- PBS phosphate buffer saline -- ROS reactive oxygen species -- SAB spontaneous alteration behavior -- SOD superoxide dismutase -- SEM standard error of the mean -- TNF-α tumor necrosis factor alpha; Brain derived neurotrophic factor -- Proinflammatory cytokines -- Imperatorin -- Lipopolysaccharide -- Neuroinflammation; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2018.04.018
• Languages: English
• ISSNs: 1043-4666

Abstract

Graphical abstract: Highlights: IMP reversed the LPS induced memory deficit in MWM and Y-maze. IMP attenuated oxidative stress and diminished acetylcholinesterase activity. IMP restored the BDNF levels and reversed the increase in TNF-α and IL-6. IMP demonstrated neuroprotective potential in LPS induced memory deficit. Abstract: Background: Lipopolysaccharide (LPS), an endotoxin from the outer membrane of Gram negative bacteria has been reported to cause neuroinflammation and learning and memory deficits. There are reports describing the beneficial effects of Imperatorin (IMP), a naturally occurring furanocoumarin in central nervous system (CNS) disorders such as anxiety and epilepsy. Objective: In the current study, we investigated whether IMP protects against LPS mediated memory deficits and neuroinflammation. Methods: Mice pretreated with IMP (5, 10 mg/kg po ) were administered LPS (250 μg/kg ip ) for 7 days. Memory was evaluated in the Morris water maze (MWM) and Y maze. The mice were euthanised and different biochemical assessments were carried out to measure oxidative stress and acetyl choline esterase (AChE). Further, evaluation of proinflammatory cytokines such as tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) levels and brain derived neurotrophic factor (BDNF) in hippocampus and cortex of brain were performed. Results: LPS administration caused poor memory retention in both, MWM and Y maze, and caused distinct oxidative stress since decrease in superoxide dismutase (SOD), reduced glutathione (GSH) levels and increased lipid peroxidation were observed. Also, a significant rise was observed in the levels of AChE. Moreover, a rise in TNF-α and IL-6 levels and depleted levels of BDNF were noted. IMP pretreatment reversed LPS induced behavioral and memory disturbances and significantly decreased the oxidative stress and AChE levels. It also reduced TNF-α and IL-6 levels and caused a significant upregulation of BDNF levels. Conclusion: Present study highlights the potential neuroprotective role of IMP against LPS mediated cognitive impairment and neuroinflammation.