Ed reactions based on EHCO3. As described, treatment with GP could reverse most metabolism-regulated gene signatures in a DMN-induced rat liver fibrosis model. Using these GP gene signatures, bioinformatics analysis predicts that GP might modulate some of the dysregulated metabolic enzymes. We next tested whether GP and its purified active fraction HHF3 might affect glycolysis. Huh7 cells were treated with various concentrations of GP and HH-F3 for 24 h. Western blot analysis indicated that GP and HH-F3 did not change the total protein expression of hexokinase 2 and pyruvate kinase muscle isozyme M2, but suppressed pyruvate dehydrogenase kinase and phosphorylated pyruvate dehydrogenase . protein expression of PGC-1. Treatment with HH-F3 suppressed 8-Br-cAMP/345627-80-7 Dex-induced PGC-1 gene expression. HH-F3 also decreased the protein levels of FOXO1 and HNF4, which were associated with gluconeogenic transcription factor expression in Hep3B/T2 cells. These results suggest that HH-F3-suppressed gluconeogenic enzyme expression may occur via inhibition of PGC-1 gene expression. HH-F3 inhibits 8-Br-cAMP/Dex-induced core PR-619 site promoter expression PGC-1 has been shown to coactivate FOXO1 and HNF4 to regulate HBV gene transcription; therefore, the activities of HBV core and X promoters were estimated upon 8-Br-cAMP/Dex treatment in the absence PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19861655 or presence of HH-F3. Interestingly, 8-BrcAMP/Dex synergistically activated hepatitis B viral core promoter activity, but had no effect on the HBV X promoter. Treatment with HH-F3 could dose dependently suppress 8-Br-cAMP/Dex-induced HBV core promoter activity in Hep3B/T2 cells. HH-F3 suppresses gluconeogenic enzymes, G6Pase and PEPCK gene expression To examine the effects of GP and HH-F3 on gluconeogenesis in HCC, the Hep3B/T2 hepatoma cell line expressing HBV was pretreated with 8-Bromo-cAMP and dexamethasone for 30 min and then was treated with HH-F3 for 24 h. All of the reagents used, including 8-Br-cAMP, dexamethasone, and HH-F3, did not affect cell viability within 24 h. Consistent with previous studies, 8-Br-cAMP/ Dex could synergistically activate gene expression of key gluconeogenic genes, 
including phosphoenol pyruvate carboxykinase and glucose-6-phosphatase, in Hep3B/T2 cells. Treatment with HH-F3 suppressed 8-Br-cAMP/Dex-induced PEPCK and G6Pase gene expression dose-dependently. Similarly, the incubation of Hep3B/T2 cells with 8-BrcAMP/Dex increased G6Pase promoter activity. Exposure to HH-F3 significantly reduced 8-Br-cAMP/Dex-induced G6Pase promoter activity. These results indicate that HH-F3 can inhibit key gluconeogenic enzyme gene expression. Overexpression of PGC-1 reverses the HH-F3-mediated decrease of HBV core promoter activity The combination of 8-Br-cAMP and Dex could synergistic stimulate 
HBV core promoter activity; thus, to identify the 8-Br-cAMP/Dex response region located within the HBV core promoter, Hep3B/T2 cells were transfected with full-length and truncated HBV core promoter constructs , and then exposed to 8-Br-cAMP/Dex. The luciferase assay indicated that the CP and CPD1 exhibited the maximum luciferase activity, which was much higher than that of CPD2 and CPD3. When nt 16561675 of CPD1 was deleted, the 8-BrcAMP/Dex-induced luciferase activity was significantly reduced. It has been reported that PGC-1 can regulate HBV gene expression in HBV transgenic mice. To address whether PGC-1 was involved in HBV core promoter activation, full-length and truncated HBV core promoter constructs were.Ed reactions based on EHCO3. As described, treatment with GP could reverse most metabolism-regulated gene signatures in a DMN-induced rat liver fibrosis model. Using these GP gene signatures, bioinformatics analysis predicts that GP might modulate some of the dysregulated metabolic enzymes. We next tested whether GP and its purified active fraction HHF3 might affect glycolysis. Huh7 cells were treated with various concentrations of GP and HH-F3 for 24 h. Western blot analysis indicated that GP and HH-F3 did not change the total protein expression of hexokinase 2 and pyruvate kinase muscle isozyme M2, but suppressed pyruvate dehydrogenase kinase and phosphorylated pyruvate dehydrogenase . protein expression of PGC-1. Treatment with HH-F3 suppressed 8-Br-cAMP/Dex-induced PGC-1 gene expression. HH-F3 also decreased the protein levels of FOXO1 and HNF4, which were associated with gluconeogenic transcription factor expression in Hep3B/T2 cells. These results suggest that HH-F3-suppressed gluconeogenic enzyme expression may occur via inhibition of PGC-1 gene expression. HH-F3 inhibits 8-Br-cAMP/Dex-induced core promoter expression PGC-1 has been shown to coactivate FOXO1 and HNF4 to regulate HBV gene transcription; therefore, the activities of HBV core and X promoters were estimated upon 8-Br-cAMP/Dex treatment in the absence PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19861655 or presence of HH-F3. Interestingly, 8-BrcAMP/Dex synergistically activated hepatitis B viral core promoter activity, but had no effect on the HBV X promoter. Treatment with HH-F3 could dose dependently suppress 8-Br-cAMP/Dex-induced HBV core promoter activity in Hep3B/T2 cells. HH-F3 suppresses gluconeogenic enzymes, G6Pase and PEPCK gene expression To examine the effects of GP and HH-F3 on gluconeogenesis in HCC, the Hep3B/T2 hepatoma cell line expressing HBV was pretreated with 8-Bromo-cAMP and dexamethasone for 30 min and then was treated with HH-F3 for 24 h. All of the reagents used, including 8-Br-cAMP, dexamethasone, and HH-F3, did not affect cell viability within 24 h. Consistent with previous studies, 8-Br-cAMP/ Dex could synergistically activate gene expression of key gluconeogenic genes, including phosphoenol pyruvate carboxykinase and glucose-6-phosphatase, in Hep3B/T2 cells. Treatment with HH-F3 suppressed 8-Br-cAMP/Dex-induced PEPCK and G6Pase gene expression dose-dependently. Similarly, the incubation of Hep3B/T2 cells with 8-BrcAMP/Dex increased G6Pase promoter activity. Exposure to HH-F3 significantly reduced 8-Br-cAMP/Dex-induced G6Pase promoter activity. These results indicate that HH-F3 can inhibit key gluconeogenic enzyme gene expression. Overexpression of PGC-1 reverses the HH-F3-mediated decrease of HBV core promoter activity The combination of 8-Br-cAMP and Dex could synergistic stimulate HBV core promoter activity; thus, to identify the 8-Br-cAMP/Dex response region located within the HBV core promoter, Hep3B/T2 cells were transfected with full-length and truncated HBV core promoter constructs , and then exposed to 8-Br-cAMP/Dex. The luciferase assay indicated that the CP and CPD1 exhibited the maximum luciferase activity, which was much higher than that of CPD2 and CPD3. When nt 16561675 of CPD1 was deleted, the 8-BrcAMP/Dex-induced luciferase activity was significantly reduced. It has been reported that PGC-1 can regulate HBV gene expression in HBV transgenic mice. To address whether PGC-1 was involved in HBV core promoter activation, full-length and truncated HBV core promoter constructs were.
