Abou El-ezz D.Maher A.Sallam N.El-brairy A.Kenawy S.Department of Pharmacology and ToxicologyFaculty of PharmacyMSA UniversityCairoEgypt; Department of BiochemistryFaculty of PharmacyMSA UniversityCairoEgypt; Department of Pharmacology and ToxicologyFaculty of PharmacyCairo UniversityCairoEgypt; Department of Physiology and PharmacologyCumming School of MedicineUniversity of CalgaryCalgaryCanada2020-01-092020-01-0920183643190https://doi.org/10.1007/s11064-018-2656-yPubMed ID 30302613https://t.ly/dNbX6ScopusTrans-cinnamaldehyde (CNM) has recently drawn attention due to its potent anti-inflammatory and antioxidant properties. The current study explored the memory enhancing effects of CNM against lipopolysaccharide (LPS)-induced neuroinflammation in mice. CNM and curcumin (a reference antioxidant) were administered at a dose of 50�mg/kg i.p.�3�h after a single LPS injection (0.8�mg/kg, i.p.) and continued daily for 7�days. Our results displayed that CNM and curcumin significantly ameliorated the LPS-induced impairment of learning and memory, neuroinflammation, oxidative stress and neuronal apoptosis. Memory functions and locomotor activity were assessed by Morris water maze, object recognition test and open field test. Both CNM and curcumin activated the nuclear factor erythroid 2 related factor 2 (Nrf2) and restored levels of downstream antioxidant enzymes superoxide dismutase and glutathione-S-transferase (GST) in the hippocampus. They also attenuated LPS-induced increase in hippocampal contents of interleukin-1? (IL-1?), malondialdehyde and caspase-3. Immunohistochemistry results showed that both CNM and curcumin reduced A?1�42 protein accumulation in brain of mice. Remarkably CNM�s effect on IL-1? was less pronounced than curcumin; however it showed higher GST activity and more potent anti-apoptotic and anti-amylodogenic effect. We conclude that, CNM produces its memory enhancing effects through modulation of Nrf2 antioxidant defense in hippocampus, inhibition of neuroinflammation, apoptosis and amyloid protein burden. � 2018, Springer Science+Business Media, LLC, part of Springer Nature.EnglishOctober University for Modern Sciences and Artsجامعة أكتوبر للعلوم الحديثة والآدابUniversity of Modern Sciences and ArtsMSA UniversityAmyloid betaCurcuminLPSNeuroinflammationNrf2Trans-cinnamaldehydeamyloid beta proteinamyloid beta protein[1-42]caspase 3cinnamaldehydecurcuminglutathione peroxidaseglutathione transferaseinterleukin 1betamalonaldehydesuperoxide dismutasetranscription factor Nrf2acroleinamyloid beta proteincinnamaldehydelipopolysaccharideNfe2l2 protein, mousetranscription factor Nrf2adultanimal experimentanimal modelanimal tissueantiinflammatory activityantioxidant activityapoptosisArticlecontrolled studyhippocampusimmunohistochemistrylipopolysaccharide-induced neuroinflammationlocomotionMorris water maze testmouseneuroprotectionnonhumanopen field testoxidative stresspriority journalprotein aggregationanalogs and derivativesanimalantagonists and inhibitorschemically induceddisease modeldrug effecthippocampusinflammationmalemaze testmetabolismpathologyphysiologyproteinosisrandomizationAcroleinAmyloid beta-PeptidesAnimalsDisease Models, AnimalHippocampusInflammationLipopolysaccharidesMaleMaze LearningMiceNF-E2-Related Factor 2Protein Aggregation, PathologicalRandom AllocationArticlehttps://doi.org/10.1007/s11064-018-2656-yPubMed ID 30302613