Linked Life Data

18452148

Source:http://linkedlifedata.com/resource/pubmed/id/18452148

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-6-3
pubmed:abstractText
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and affects millions of people worldwide. Despite the increasing prevalence of NAFLD, the exact molecular/cellular mechanisms remain obscure and effective therapeutic strategies are still limited. It is well-accepted that free fatty acid (FFA)-induced lipotoxicity plays a pivotal role in the pathogenesis of NAFLD. Inhibition of FFA-associated hepatic toxicity represents a potential therapeutic strategy. Glycyrrhizin (GL), the major bioactive component of licorice root extract, has a variety of pharmacological properties including anti-inflammatory, antioxidant, and immune-modulating activities. GL has been used to treat hepatitis to reduce liver inflammation and hepatic injury; however, the mechanism underlying the antihepatic injury property of GL is still poorly understood. In this report, we provide evidence that 18 beta-glycyrrhetinic acid (GA), the biologically active metabolite of GL, prevented FFA-induced lipid accumulation and cell apoptosis in in vitro HepG2 (human liver cell line) NAFLD models. GA also prevented high fat diet (HFD)-induced hepatic lipotoxicity and liver injury in in vivo rat NAFLD models. GA was found to stabilize lysosomal membranes, inhibit cathepsin B expression and enzyme activity, inhibit mitochondrial cytochrome c release, and reduce FFA-induced oxidative stress. These characteristics may represent major cellular mechanisms, which account for its protective effects on FFA/HFD-induced hepatic lipotoxicity. CONCLUSION: GA significantly reduced FFA/HFD-induced hepatic lipotoxicity by stabilizing the integrity of lysosomes and mitochondria and inhibiting cathepsin B expression and enzyme activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1527-3350
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1905-15
pubmed:meshHeading
pubmed-meshheading:18452148-Animals, pubmed-meshheading:18452148-Anti-Inflammatory Agents, pubmed-meshheading:18452148-Apoptosis, pubmed-meshheading:18452148-Cathepsin B, pubmed-meshheading:18452148-Cell Line, pubmed-meshheading:18452148-Cells, Cultured, pubmed-meshheading:18452148-Cytochromes c, pubmed-meshheading:18452148-Dietary Fats, pubmed-meshheading:18452148-Disease Models, Animal, pubmed-meshheading:18452148-Fatty Acids, Nonesterified, pubmed-meshheading:18452148-Fatty Liver, pubmed-meshheading:18452148-Glycyrrhetinic Acid, pubmed-meshheading:18452148-Hepatocytes, pubmed-meshheading:18452148-Humans, pubmed-meshheading:18452148-Lipid Metabolism, pubmed-meshheading:18452148-Lysosomes, pubmed-meshheading:18452148-Male, pubmed-meshheading:18452148-Mitochondria, Liver, pubmed-meshheading:18452148-Rats, pubmed-meshheading:18452148-Rats, Sprague-Dawley
pubmed:year
2008
pubmed:articleTitle
Prevention of free fatty acid-induced hepatic lipotoxicity by 18beta-glycyrrhetinic acid through lysosomal and mitochondrial pathways.
pubmed:affiliation
Jiangsu Center for Drug Screening, Jiangsu Center for Pharmacodynamic Research and Evaluation, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural