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.
Highlights
Alzheimer's disease (AD) is the most common human neurodegenerative disorder and the main cause of dementia among the elderly
Neuritic plaques are composed of aggregates of Aβ protein, a 40–43 amino acid proteolytic fragment derived from the amyloid precursor protein that is over-expressed in AD while NFTs are composed of hyperphosphorylated microtubule-associated protein tau [1,2]
We examined if oral administration of ground Cinnamonum verum in 5XFAD transgenic (Tg) mice increased the level of NaB in the hippocampus
Summary
Alzheimer's disease (AD) is the most common human neurodegenerative disorder and the main cause of dementia among the elderly. The majority of AD cases (90–95%) are sporadic and the remainder familial. Neuropathologically, in both cases, the disease is characterized by two hallmark lesions: neurofibrillary tangles and neuritic plaques. Malondialdehyde and 4-hydroxynonenal, products of lipid peroxidation, are increased in multiple brain regions of patients with AD or mild cognitive impairment (MCI) [6]. Oxidative stress is known stimulate the production of Aβ1-40/42 in the CNS of AD patients via increasing the activation of β- and γ-secretase and decreasing the activity of α-secretase [3,7]. Attenuation of oxidative stress in the CNS of AD patients is an important area of research
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