Abstract
Rosmarinic acid (RA), a polyphenol found in Lamiaceae herbs, is a candidate of preventive ingredients against Alzheimer’s disease (AD) as it potently suppresses the aggregation of amyloid β (Aβ); however, the effect of RA on tau phosphorylation and cognitive dysfunction remains unclear. The present study revealed that RA intake inhibited the pathological hallmarks of AD, including Aβ and phosphorylated tau accumulation, and improved cognitive function in the 3 × Tg-AD mouse model. Additionally, RA intake suppressed hippocampal inflammation and led to the downregulation of the JNK signaling pathway that induces tau phosphorylation. Feeding with RA exerted an anti-inflammatory effect not only in the central nervous system but also in the periphery. Downregulation of the JNK signaling pathway in hippocampus may be a potential mechanism underlying the inhibition of progression of pathology and cognitive deficit by RA feeding.
Highlights
Alzheimer’s disease (AD) is clinically characterized as progressive dementia with the pathological hallmarks of senile plaques and neurofibrillary tangles comprising amyloid-β peptide (Aβ) and hyperphosphorylated tau (p-tau), respectively
The creatine kinase levels tended to be higher in the rosmarinic acid (RA) group while there were no significant differences in the levels of other plasma proteins between the two groups (Supplementary Table S2)
We focused on inflammation-related pathways such as the transforming growth factor-beta signaling pathway and the tumor necrosis factor (TNF) signaling pathway because of the chronic inflammation had reported in the brains of patients with AD15
Summary
Alzheimer’s disease (AD) is clinically characterized as progressive dementia with the pathological hallmarks of senile plaques and neurofibrillary tangles comprising amyloid-β peptide (Aβ) and hyperphosphorylated tau (p-tau), respectively. The currently available drugs temporarily relieve symptoms without providing cure for AD. Food components that can contribute to the prevention of AD are attracting attention. Several epidemiological studies indicate that a polyphenol-rich diet reduces the risk of AD1,2. Rosmarinic acid (RA) is a promising anti-AD agent because it strongly inhibits Aβ aggregation and alleviates synaptic toxicity in vitro[3]. RA binds to the β-sheet structure of Aβ and directly inhibits its aggregation in vitro[3]. RA is a phenylpropanoid polyphenol found in members of the Lamiaceae herb family such as rosemary and lemon balm (Fig. 1a)
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