Cinnamon and Its Metabolite Sodium Benzoate Attenuate the Activation of p21rac and Protect Memory and Learning in an Animal Model of Alzheimer’s Disease

• Published in: PloS one Vol. 10; no. 6; p. e0130398
• Main Authors: Modi, Khushbu K., Roy, Avik, Brahmachari, Saurabh, Rangasamy, Suresh B., Pahan, Kalipada
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.06.2015; Public Library of Science (PLoS)
• Subjects: Activation; Administration, Oral; Alzheimer Disease - metabolism; Alzheimer Disease - psychology; Alzheimer's disease; Amino acids; Animal cognition; Animal models; Animals; Antioxidants; Apoptosis; Attenuation; Brain research; Cell culture; Cell Line; Cholesterol; Cinnamomum zeylanicum; Cinnamon; Cognitive ability; Disease Models, Animal; Flavors; Glutathione; GTP-binding protein; Hippocampus; Hippocampus - metabolism; Homocysteine; Humans; Intermediates; Learning; Learning - drug effects; Lipid peroxidation; Lipopolysaccharides; Maze Learning; Memory; Memory - drug effects; Metabolites; Mevalonate pathway; Mevalonic acid; Mice; Mice, Transgenic; Microglia; Microglia - metabolism; Microglial cells; Neuronal-glial interactions; Nitrotyrosine; Older people; Oxidation; Oxidative Stress; Oxygen; Peptides; Powder; Proteins; R&D; rac GTP-Binding Proteins - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Research & development; Sodium; Sodium benzoate; Sodium Benzoate - metabolism; Sodium formate; Transgenic mice; United States > US; Chicago Illinois
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0130398

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.