title: Water Extract of Dolichos lablab Attenuates Hepatic Lipid Accumulation in a Cellular Nonalcoholic Fatty Liver Disease Model.
abstract: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that is rising in prevalence worldwide. Therapeutic strategies for patients with NAFLD are limited by a lack of effective drugs. In this report, we show that Dolichos lablab water extract (DLL-Ex) protects against free fatty acid (FFA)-induced lipid accumulation and attenuates expression of genes involved in lipid droplet accumulation in cellular NAFLD models. The hepatoprotective effects and underlying mechanism of DLL-Ex were assessed using an in vitro cellular model in which NAFLD was simulated by inducing excessive FFA influx into hepatocytes. HepG2 cells were treated with DLL-Ex and FFAs for 24 h, after which intracellular lipid content was observed by using Nile Red and Oil Red O staining. Quantitative real-time polymerase chain reaction was used to measure expression levels of genes related to FFA-mediated cellular energy depletion. Western blotting was used to measure protein levels of phosphorylated c-Jun N-terminal kinase, AMP-activated protein kinase alpha (AMPKα), and peroxisome proliferator-activated receptor γ coactivator 1 alpha. In HepG2 cells, DLL-Ex inhibited expression of CD36, which regulates fatty acid uptake, as well as BODIPY-labeled fatty acid uptake. Additionally, DLL-Ex significantly attenuated FFA-mediated cellular energy depletion and mitochondrial membrane depolarization. Furthermore, DLL-Ex enhanced phosphorylation of AMPK, indicating that AMPK is a critical regulator of DLL-Ex-mediated inhibition of hepatic lipid accumulation, possibly through its antioxidative effect. These results demonstrate that DLL-Ex exerts potent anti-NAFLD activity, suggesting that it could be a potential adjuvant treatment for patients with NAFLD.
authors.affiliation: 1 KM Convergence Research Division, Korea Institute of Oriental Medicine , Daejeon, Korea.
authors.forename: A-Rang
authors.initials: AR
authors.lastname: Im
authors.affiliation: 1 KM Convergence Research Division, Korea Institute of Oriental Medicine , Daejeon, Korea.
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: 1 KM Convergence Research Division, Korea Institute of Oriental Medicine , Daejeon, Korea.
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Lee
authors.affiliation: 2 Mibyeong Research Center, Korea Institute of Oriental Medicine , Daejeon, Korea.|3 University of Science and Technology , Daejeon, Korea.
authors.forename: Kwang Hoon
authors.initials: KH
authors.lastname: Song
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D031294:Dolichos / Q000737:chemistry*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000008:administration & dosage*
chemical_list: D005230:Fatty Acids, Nonesterified; D047495:PPAR gamma; D010936:Plant Extracts; D048031:JNK Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Dolichos lablab; free fatty acid; nonalcoholic fatty liver disease