Arctigenin protects against steatosis in WRL68 hepatocytes through activation of phosphoinositide 3-kinase/protein kinase B and AMP-activated protein kinase pathways

• Published in: Nutrition research (New York, N.Y.) N.Y.), 2018-04, Vol.52, p.87-97
• Main Authors: Chen, Kung-Yen, Lin, Jui-An, Yao, Han-Yun, Hsu, An-Chih, Tai, Yu-Ting, Chen, Jui-Tai, Hsieh, Mao-Chih, Shen, Tang-Long, Hsu, Ren-Yi, Wu, Hong-Tan, Wang, Guey Horng, Ho, Bing-Ying, Chen, Yu-Pei
• Format: Article
• Language: English
• Subjects: Acetyl-CoA Carboxylase - metabolism; AMP-Activated Protein Kinases - metabolism; Arctigenin; Arctium - chemistry; Carnitine O-Palmitoyltransferase - metabolism; Fatty Liver - metabolism; Fatty Liver - prevention & control; Furans - pharmacology; Furans - therapeutic use; Hep G2 Cells; Hepatocytes - drug effects; Hepatocytes - metabolism; Humans; Inflammation; Inflammation - metabolism; Inflammation - prevention & control; Intercellular Adhesion Molecule-1 - metabolism; Interleukins - metabolism; Lignans - pharmacology; Lignans - therapeutic use; Lipotoxicity; Liver - cytology; Liver - drug effects; Liver - metabolism; Liver - pathology; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - prevention & control; Nonalcoholic fatty liver disease; Oleic Acid - metabolism; Oxidative Stress - drug effects; Phosphatidylinositol 3-Kinase - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; PPAR alpha - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Steatosis; Sterol Regulatory Element Binding Protein 1 - metabolism
• ISSN: 0271-5317; 1879-0739
• DOI: 10.1016/j.nutres.2018.02.004

Arctigenin (ATG), a lignin extracted from Arctium lappa (L.), exerts antioxidant and anti-inflammatory effects. We hypothesized that ATG exerts a protective effect on hepatocytes by preventing nonalcoholic fatty liver disease (NAFLD) progression associated with lipid oxidation–associated lipotoxicity and inflammation. We established an in vitro NAFLD cell model by using normal WRL68 hepatocytes to investigate oleic acid (OA) accumulation and the potential bioactive role of ATG. The results revealed that ATG inhibited OA-induced lipid accumulation, lipid peroxidation, and inflammation in WRL68 hepatocytes, as determined using Oil Red O staining, thiobarbituric acid reactive substance assay, and inflammation antibody array assays. Quantitative RT-PCR analysis demonstrated that ATG significantly mitigated the expression of acetylcoenzyme A carboxylase 1 and sterol regulatory element-binding protein-1 and significantly increased the expression of carnitine palmitoyltransferase 1 and peroxisome proliferator-activated receptor alpha. The 40 targets of the Human Inflammation Antibody Array indicated that ATG significantly inhibited the elevation of the U937 lymphocyte chemoattractant, ICAM-1, IL-1β, IL-6, IL-6sR, IL-7, and IL-8. ATG could activate the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK) pathways and could increase the phosphorylation levels of Akt and AMPK to mediate cell survival, lipid metabolism, oxidation stress, and inflammation. Thus, we demonstrated that ATG could inhibit NAFLD progression associated with lipid oxidation–associated lipotoxicity and inflammation, and we provided insights into the underlying mechanisms and revealed potential targets to enable a thorough understanding of NAFLD progression.