Abstract
Alzheimer disease (AD) is a neurodegenerative disorder characterized by excessive accumulation of amyloid-beta peptide (Aβ) and progressive loss of neurons. Therefore, the inhibition of Aβ-induced neurotoxicity is a potential therapeutic approach for the treatment of AD. Ecklonia cava is an edible brown seaweed, which has been recognized as a rich source of bioactive derivatives, mainly phlorotannins. In this study, phlorotannins including eckol, dieckol, 8,8′-bieckol were used as potential neuroprotective candidates for their anti-apoptotic and anti-inflammatory effects against Aβ25-35-induced damage in PC12 cells. Among the tested compounds, dieckol showed the highest effect in both suppressing intracellular oxidative stress and mitochondrial dysfunction and activation of caspase family. Three phlorotannins were found to inhibit TNF-α, IL-1β and PGE2 production at the protein levels. These result showed that the anti-inflammatory properties of our compounds are related to the down-regulation of proinflammatory enzymes, iNOS and COX-2, through the negative regulation of the NF-κB pathway in Aβ25-35-stimulated PC12 cells. Especially, dieckol showed the strong anti-inflammatory effects via suppression of p38, ERK and JNK. However, 8,8′-bieckol markedly decreased the phosphorylation of p38 and JNK and eckol suppressed the activation of p38. Therefore, the results of this study indicated that dieckol from E. cava might be applied as a drug candidate for the development of new generation therapeutic agents against AD.
Highlights
Alzheimer’s disease (AD) is one of the most serious neurodegenerative disorders in the aged population
The neuropathological hallmarks of AD are characterized by amyloid plaques and neurofibrillary tangles (NFTs) composed of aggregated β-amyloid peptides (Aβ) and microtubule-associated protein tau, respectively [1]
PC12 cells were supplied from American Type Culture Collection (ATCC)
Summary
Alzheimer’s disease (AD) is one of the most serious neurodegenerative disorders in the aged population. The neuropathological hallmarks of AD are characterized by amyloid plaques and neurofibrillary tangles (NFTs) composed of aggregated β-amyloid peptides (Aβ) and microtubule-associated protein tau, respectively [1]. The abnormal phosphorylated tau protein is toxic to neurons and disrupts microtubulin, leading to axonal transport dysfunction and inhibition of proteasome activity, impairment of the structure and function of neurons, and AD [2,3]. Mar. Drugs 2019, 17, 7; doi:10.3390/md17010007 www.mdpi.com/journal/marinedrugs. Mar. Drugs 2019, 17, 7 and is more specific to AD, because tauopathy is observed in other neurodegenerative disorders, such as frontotemporal dementia and dementia with Lewy bodies [4]
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