Anti-oxidation And Anti-inflammatory Effects Of Eicosapentaenoic Acid (EPA)

Reactive Oxygen Species(ROS)is a series of oxygen-bearing single-electron reduction products,which is mainly produced by the mitochondrial respiratory chain during the body’s metabolism.Excessive accumulation of ROS can cause oxidative stress,resulting in mitochondrial dysfunction and impairing mitochondrial biosynthesis,which may eventually lead to a variety of diseases.Eicosapentaenoic acid(EPA)is an essential omega-3 polyunsaturated fatty acid for human.It has various physiological functions such as improving immunity,anti-tumor and reducing cardiovascular diseases,however,its antioxidant and anti-inflammatory activities are still controversial and the mechanism is unclear.The current research aims to investigate the antioxidant and anti-inflammatory activities of EPA in cultured cells,and further determine the regulatory effect of EPA in mitochondria and the effect of mitochondrial miRNA on oxidative stress.The main research results are as follows:(1)EPA improved the antioxidant capacity of Hep G2 cells: upon 48 h EPA treatment,the intracellular ROS level was significantly reduced by about 60%;the total cellular antioxidant capacity was increased by about 70 %;the activity and gene expression levels of major antioxidant enzymes,including superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GPX),were also significantly increased.(2)EPA improved the mitochondrial function and promotes mitochondrial biosynthesis in Hep G2 cells: after 48 h EPA treatment,the mitochondrial ROS level was significantly reduced by about 70 %;the ratio of ADP/ATP was increased by about 30 %;the mitochondrial membrane potential was increased by about 3.5 folds.In addition,the mitochondrial copy number,the expression of mitochondrial coding genes,transcription factors,and fission fusion factors were all upregulated.(3)EPA treatment increased the expression of mi R-708-5p and reduced the expression of let-7c-3p in Hep G2 cells.Both overexpressing mi R-708-5p and inhibiting let-7c-3p reduced ROS level,increased the activity of major antioxidant enzymes and alleviate cellular oxidative stress.(4)EPA showed anti-inflammatory activity.It reduced the release of inflammation mediator Nitric Oxide(NO),as well as the activity and expression of inducible nitric oxide synthase(i NOS).EPA treatment also reduced the release and gene expression of pro-inflammatory factors interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α),as well as inducing the release and gene expression of anti-inflammatory factors interleukin-10(IL-10)in lipopolysaccharide-induced inflammatory RAW264.7 cells.Therefore,EPA may regulate oxidative stress and inflammation by controlling mitochondrial functions,enhancing mitochondrial biosynthesis and modulating mitochondrial miRNA expression.This study may shed light on the development and application of ω-3 unsaturated fatty acid-related products and their role in improving human immunity and preventing diseases.