title: Puerarin ameliorates hepatic steatosis by activating the PPARα and AMPK signaling pathways in hepatocytes.
abstract: Non-alcoholic fatty liver disease (NAFLD) is characterized by the hepatic manifestation of metabolic syndrome and is the leading cause of chronic liver disease. Steatohepatitis plays a critical role in the process resulting in liver fibrosis and cirrhosis. Puerarin is a herbal product widely used in Asia, and is believed to have therapeutic benefits for alleviating the symptoms of steatohepatitis. The present study was designed to investigate the effects and mechanisms of action of puerarin in reducing lipid accumulation in oleic acid (OA)-treated HepG2 cells. Hepatocytes were treated with OA with or without puerarin to observe lipid accumulation by Oil Red O staining. We also examined hepatic lipid contents (e.g., triacylglycerol and cholesterol) following treatment with puerarin. Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were used to measure sterol regulatory element binding protein (SREBP)-1, fatty acid synthase (FAS), peroxisome proliferator-activated receptor α (PPARα) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) protein and mRNA expression, respectively. Our results revealed that puerarin suppressed OA-induced lipid accumulation, and reduced the triacylglycerol and cholesterol levels. Furthermore, puerarin decreased the expression levels of lipogenic enzymes, such as FAS and SREBPs, and increased the expression levels of PPARα, which are critical regulators of hepatic lipid metabolism through the AMPK signaling pathway. These results indicate that puerarin has the same ability to activate AMPK, and reduce SREBP-1 and FAS expression, thus inhibiting hepatic lipogenesis and increasing hepatic antioxidant activity. We found that puerarin exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in hepatocytes. Therefore, puerarin extract may have therapeutic benefits in the treatment of fatty liver and lipid-related metabolic disorders.
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Ok-Hwa
authors.initials: OH
authors.lastname: Kang
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Sung-Bae
authors.initials: SB
authors.lastname: Kim
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Mun
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Yun-Soo
authors.initials: YS
authors.lastname: Seo
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Hyeong-Chil
authors.initials: HC
authors.lastname: Hwang
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Ho-Seob
authors.initials: HS
authors.lastname: Lee
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Dae-Gil
authors.initials: DG
authors.lastname: Kang
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Dong-Yeul
authors.initials: DY
authors.lastname: Kwon
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D005234:Fatty Liver / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D019301:Oleic Acid / Q000494:pharmacology; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D007529:Isoflavones; D047493:PPAR alpha; D012333:RNA, Messenger; D019301:Oleic Acid; D055372:AMP-Activated Protein Kinases; C033607:puerarin