Bavachinin inhibits cholesterol synthesis enzyme FDFT1 expression via AKT/mTOR/SREBP-2 pathway |
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| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is a progressive and chronic liver disease. No effective drug is currently approved for the treatment of NAFLD. Traditionally it is thought that pathogenesis of NAFLD develops from some imbalance in lipid control, thereby leading to hepatotoxicity and disease development. Squalene synthase (SQS), encoded by FDFT1, is a key regulator in cholesterol synthesis and thus a potential target for the treatment of NAFLD. Here we could identify bavachinin, a component from traditional Chinese medicine Fructus Psoraleae (FP), which apparently protects HepaRG cells from palmitic acid induced death, suppressing lipid accumulation and cholesterol synthesis through inhibition of FDFT1 through the AKT/mTOR/SREBP-2 pathway. Over-expression of FDFT1 abolished bavachinin (BVC) -induced inhibition of cholesterol synthesis. The data presented here suggest that bavachinin acts as a cholesterol synthesis enzyme inhibitor, and might serve as a drug for treating NAFLD in the future. |
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| Keywords: | Bavachinin Cholesterol synthesis inhibition Squalene synthase HMG-CoA synthase ACAT" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" Acyl CoA-cholesterol acyltransferase AKT" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" Serine/threonine kinase Akt ALT" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" Alanine aminotransferase BVC" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" Bavachinin CDS" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" Coding DNA sequence DEP" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" Differentially expressed protein FC" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" Free cholesterol FP" },{" #name" :" keyword" ," $" :{" id" :" k0105" }," $$" :[{" #name" :" text" ," $$" :[{" #name" :" italic" ," _" :" Fructus Psoraleae HDL" },{" #name" :" keyword" ," $" :{" id" :" k0115" }," $$" :[{" #name" :" text" ," _" :" High-density lipoprotein HMG-CoA" },{" #name" :" keyword" ," $" :{" id" :" k0125" }," $$" :[{" #name" :" text" ," _" :" 3-hydroxy-3-methylglutaryl coenzyme A HRP" },{" #name" :" keyword" ," $" :{" id" :" k0135" }," $$" :[{" #name" :" text" ," _" :" Horseradish Peroxidase IGF-1" },{" #name" :" keyword" ," $" :{" id" :" k0145" }," $$" :[{" #name" :" text" ," _" :" Insulin-like growth factor 1 JNK" },{" #name" :" keyword" ," $" :{" id" :" k0155" }," $$" :[{" #name" :" text" ," _" :" C-Jun N-terminal kinase LDL" },{" #name" :" keyword" ," $" :{" id" :" k0165" }," $$" :[{" #name" :" text" ," _" :" Low-density lipoprotein MMP" },{" #name" :" keyword" ," $" :{" id" :" k0175" }," $$" :[{" #name" :" text" ," _" :" Mitochondrial membrane potential mTOR" },{" #name" :" keyword" ," $" :{" id" :" k0185" }," $$" :[{" #name" :" text" ," _" :" Mammalian target of rapamycin MTT" },{" #name" :" keyword" ," $" :{" id" :" k0195" }," $$" :[{" #name" :" text" ," _" :" Methylthiazolyldiphenyl-tetrazolium bromide NAFLD" },{" #name" :" keyword" ," $" :{" id" :" k0205" }," $$" :[{" #name" :" text" ," _" :" Non-alcoholic fatty liver disease ORO" },{" #name" :" keyword" ," $" :{" id" :" k0215" }," $$" :[{" #name" :" text" ," _" :" Oil red O PA" },{" #name" :" keyword" ," $" :{" id" :" k0225" }," $$" :[{" #name" :" text" ," _" :" Palmitic acid PKR" },{" #name" :" keyword" ," $" :{" id" :" k0235" }," $$" :[{" #name" :" text" ," _" :" Protein kinase R ROS" },{" #name" :" keyword" ," $" :{" id" :" k0245" }," $$" :[{" #name" :" text" ," _" :" Reactive oxygen species RT" },{" #name" :" keyword" ," $" :{" id" :" k0255" }," $$" :[{" #name" :" text" ," _" :" Room temperature SDS-PAGE" },{" #name" :" keyword" ," $" :{" id" :" k0265" }," $$" :[{" #name" :" text" ," _" :" Sodium dodecyl sulphate-polyacrylamide gel electrophoresis SQS" },{" #name" :" keyword" ," $" :{" id" :" k0275" }," $$" :[{" #name" :" text" ," _" :" Squalene synthase SREBP" },{" #name" :" keyword" ," $" :{" id" :" k0285" }," $$" :[{" #name" :" text" ," _" :" Sterol regulatory element binding protein TBST" },{" #name" :" keyword" ," $" :{" id" :" k0295" }," $$" :[{" #name" :" text" ," _" :" Tris-buffered saline tween-20 TC" },{" #name" :" keyword" ," $" :{" id" :" k0305" }," $$" :[{" #name" :" text" ," _" :" Total cholesterol VLDL" },{" #name" :" keyword" ," $" :{" id" :" k0315" }," $$" :[{" #name" :" text" ," _" :" Very low-density lipoprotein |
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