Inhibitory effect of ethanol extract of Nannochloropsis oceanica on lipopolysaccharide-induced neuroinflammation, oxidative stress, amyloidogenesis and memory impairment.

Ji Yeon Choi,Hee Pom Lee,Jin Tae Hong,Hee Sik Kim,Sang-Bae Han,Chul Ju Hwang

doi:10.18632/oncotarget.17268

Abstract

Oxidative stress and neuroinflammation is implicated in the pathogenesis and development of Alzheimer's disease (AD). Here, we investigated the suppressive possibility of ethanol extract of Nannochloropsis oceanica (N. oceanica) on memory deficiency along with the fundamental mechanisms in lipopolysaccharide (LPS)-treated mice model. Among several extracts of 32 marine microalgae, ethanol extract of N. oceanica showed the most significant inhibitory effect on nitric oxide (NO) generation, NF-κB activity and β-secretase activity in cultured BV-2 cells, neuronal cells and Raw 264.7 cells. Ethanol extract of N. oceanica (50, 100 mg/kg) also ameliorated LPS (250 μg/kg)-induced memory impairment. We also found that ethanol extract of N. oceanica inhibited the LPS-induced expression of iNOS and COX-2. Furthermore, the production of reactive oxygen species (ROS), malondialdehyde (MDA) level as well as glutathione (GSH) level was also decreased by treatment of ethanol extract of N.oceanica. The ethanol extract of N. oceanica also suppresses IκB degradation as well as p50 and p65 translocation into the nucleus in LPS-treated mice brain. Associated with the inhibitory effect on neuroinflammation and oxidative stress, ethanol extract of N. oceanica suppressed Aβ1-42 generation through down-regulation of APP and BACE1 expression in in vivo. These results suggest that ethanol extract of N. oceanica ameliorated memory impairment via anti-inflammatory, anti-oxidant and anti-amyloidogenic mechanisms.

Highlights

In recent years, algae have been the oldest living organisms on earth and considered a rich and sustainable source of bioactive compounds such as antioxidants, vitamins, carotenoids as well as fatty acids and amino acids and utilized for biomass as food and feed additives [1, 2]
32 marine microalgae were extracted with several different solvents such as ethanol, hexane and ethyl acetate. 20 μg/mL of extracts were tested for their inhibitory effects on nitric oxide (NO) generation, NF- κB and β-secretase activities
We found that ethanol extract of N. oceanica suppressed neuroinflammation, oxidative www.impactjournals.com/oncotarget

Summary

Introduction

Algae have been the oldest living organisms on earth and considered a rich and sustainable source of bioactive compounds such as antioxidants, vitamins, carotenoids as well as fatty acids and amino acids and utilized for biomass as food and feed additives [1, 2]. Including oceanica strain has been identified as well-known sources of eicosapentaenoic acids (EPA), docosahexaenoic acids (DHA), and etc, that are important polyunsaturated fatty acids [16] These omega-3 unsaturated fatty acids have been reported to www.impactjournals.com/oncotarget protect against generation of oxidative stress in neural cells [17] and against dementia including Alzheimer’s disease (AD) [18]. EPA and DHA possess healthpromoting effects and preventive activity of cancer, atherosclerosis, heart disease, arthritis and psoriasis [2, 19] They are important in the brain and blood vessels and are considered to be vital for brain and retina development [2, 20]. It was reported that Nannochloropsis oceanica (N.oceanica) has significantly promoted antioxidant activity in the amyloid beta-induced oxidative stress in neuronal cells and higher radical scavenging activity [21, 24]. We expect EPA from microalgae based on their anti-oxidant and antiinflammatory activities which could be a promising tool for the prevention of inflammatory diseases

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Conclusion