title: Cinnamon and Its Metabolite Sodium Benzoate Attenuate the Activation of p21rac and Protect Memory and Learning in an Animal Model of Alzheimer's Disease.
abstract: This study underlines the importance of cinnamon, a commonly used natural spice and flavoring material, and its metabolite sodium benzoate (NaB) in attenuating oxidative stress and protecting memory and learning in an animal model of Alzheimer's disease (AD). NaB, but not sodium formate, was found to inhibit LPS-induced production of reactive oxygen species (ROS) in mouse microglial cells. Similarly, NaB also inhibited fibrillar amyloid beta (Aβ)- and 1-methyl-4-phenylpyridinium(+)-induced microglial production of ROS. Although NaB reduced the level of cholesterol in vivo in mice, reversal of the inhibitory effect of NaB on ROS production by mevalonate, and geranylgeranyl pyrophosphate, but not cholesterol, suggests that depletion of intermediates, but not end products, of the mevalonate pathway is involved in the antioxidant effect of NaB. Furthermore, we demonstrate that an inhibitor of p21rac geranylgeranyl protein transferase suppressed the production of ROS and that NaB suppressed the activation of p21rac in microglia. As expected, marked activation of p21rac was observed in the hippocampus of subjects with AD and 5XFAD transgenic (Tg) mouse model of AD. However, oral feeding of cinnamon (Cinnamonum verum) powder and NaB suppressed the activation of p21rac and attenuated oxidative stress in the hippocampus of Tg mice as evident by decreased dihydroethidium (DHE) and nitrotyrosine staining, reduced homocysteine level and increased level of reduced glutathione. This was accompanied by suppression of neuronal apoptosis, inhibition of glial activation, and reduction of Aβ burden in the hippocampus and protection of memory and learning in transgenic mice. Therefore, cinnamon powder may be a promising natural supplement in halting or delaying the progression of AD.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, United States of America.
authors.forename: Khushbu K
authors.initials: KK
authors.lastname: Modi
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, United States of America.
authors.forename: Avik
authors.initials: A
authors.lastname: Roy
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, United States of America.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Brahmachari
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, United States of America.
authors.forename: Suresh B
authors.initials: SB
authors.lastname: Rangasamy
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, United States of America; Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, 820 South Damen Avenue, Chicago, United States of America.
authors.forename: Kalipada
authors.initials: K
authors.lastname: Pahan
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D002460:Cell Line; D002935:Cinnamomum zeylanicum; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007858:Learning / Q000187:drug effects*; D018782:Maze Learning; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D020160:Sodium Benzoate / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D020744:rac GTP-Binding Proteins; D020160:Sodium Benzoate