ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg·d) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.
Subject(s)
Animals , Male , Rats , Alanine Transaminase , Blood , Aspartate Aminotransferases , Blood , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors , Genetics , Diabetes Mellitus, Type 2 , Blood , Drug Therapy , Metabolism , Diet, High-Fat , Disease Models, Animal , Down-Regulation , Insulin , Blood , Insulin Resistance , Physiology , Lipid Metabolism , Genetics , Liver , Morus , Non-alcoholic Fatty Liver Disease , Blood , Drug Therapy , Metabolism , Phytotherapy , Plant Extracts , Pharmacology , Therapeutic Uses , Rats, Sprague-Dawley , StreptozocinABSTRACT
Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg·d) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.
Subject(s)
Animals , Male , Rats , Alanine Transaminase , Blood , Aspartate Aminotransferases , Blood , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors , Genetics , Diabetes Mellitus, Type 2 , Blood , Drug Therapy , Metabolism , Diet, High-Fat , Disease Models, Animal , Down-Regulation , Insulin , Blood , Insulin Resistance , Physiology , Lipid Metabolism , Genetics , Liver , Morus , Non-alcoholic Fatty Liver Disease , Blood , Drug Therapy , Metabolism , Phytotherapy , Plant Extracts , Pharmacology , Therapeutic Uses , Rats, Sprague-Dawley , StreptozocinABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanism of all trans retinoid acid (ATRA) inhibition of cell growth and induction of apoptosis in human retinoblastoma Y79 cells.</p><p><b>METHODS</b>Antiproliferating effects of ATRA on Y79 cells were studied by (3)H-thymidine incorporation. Cell cycle analysis was performed by flow cytometry, apoptosis of the ATRA-treated cells was determined by DNA fragmentation analysis and JNK phosphorylation analyzed by Western blot.</p><p><b>RESULTS</b>After 36h treatment of 1 micro mol/L ATRA, (3)H-thymidine incorporation decreased to 40% with Y79 cells arrested in G(0)/G(1) and Sub-G(1) peak appeared. DNA ladder was observed in DNA fragmentation analysis after 36h treatment of ATRA. Curcumin, a JNK blocker, blocked the apoptosis and the growth inhibition induced by ATRA. JNK was phosphorylated in 10 to 20 min.</p><p><b>CONCLUSION</b>ATRA can induce the apoptosis in Y79 cells by phosphorylation of JNK, which suggests that ATRA may have clinical application prospects for treatment of retinoblastoma.</p>