AIM:To investigate the in vivo hepatoprotective effects and mechanisms of Gentiana manshurica Kitagawa (GM) in acetaminophen (APAP)-induced liver injury in mice.METHODS: GM (200, 150 or 50 mg/kg body weight) or N-acet...AIM:To investigate the in vivo hepatoprotective effects and mechanisms of Gentiana manshurica Kitagawa (GM) in acetaminophen (APAP)-induced liver injury in mice.METHODS: GM (200, 150 or 50 mg/kg body weight) or N-acetyl-L-cysteine (NAC; 300 mg/kg body weight) was administrated orally with a single dose 2 h prior to APAP (300 mg/kg body weight) injection in mice.RESULTS: APAP treatment significantly depleted hepatic glutathione (GSH), increased serum aspartate aminot ransferase (AST), alanine aminotransferase (ALT) and malonyldialdehyde (MDA) and 4-hydroxynonenal levels, and decreased hepatic activity of glutathione peroxidase (GSH-px) and superoxide dismutase (SOD). However, the pretreatment of GM signif icantly alleviated APAP-induced oxidative stress by increasing GSH content, decreasing serum ALT, AST and MDA, and retaining the activity of GSH-px and SOD in the liver. Furthermore, GM pretreatment can inhibit caspase-3 activation and phosphorylation of c-Jun-NH2-terminal protein kinase 2 (JNK1/2) and extracellular signalregulated kinase (ERK). GM also remarkably attenuated hepatocyte apoptosis confirmed by the terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling method.CONCLUSION: Hepatoprotective effects of GM against APAP-induced acute toxicity are mediated either by preventing the decline of hepatic antioxidant status or its direct anti-apoptosis capacity. These results support that GM is a potent hepatoprotective agent.展开更多
HepatitisBvirus(HBV)infection causes acuteand chronic liver diseases,but is not directly cytopathic.Liver injury results fromrepeated attempts of the cellular immune response system to control the viral infection.Here...HepatitisBvirus(HBV)infection causes acuteand chronic liver diseases,but is not directly cytopathic.Liver injury results fromrepeated attempts of the cellular immune response system to control the viral infection.Here,we investigate the roles of cellular factors and signaling pathways involved in the regulation of HBV replication to reveal the mechanism underlying HBV infection and pathogenesis.Weshowthat collagen triple helix repeat containing 1(CTHRC1)expression is elevated in HBV-infected patients andin HBV-transfected cells through epigenetic modification and transcriptional regulation.CTHRC1 facilitates HBV replication in cultured cells and BALB/c mice by activating the PKCa/ERK/JNK/c-Jun cascade to repress the IFN/JAK/STAT pathway.HBV-activated CTHRC1 downregulates the activityof typeI interferon(IFN),theproductionof IFN-stimulatedgenes(ISGs),andthephosphorylationofsignal transducerandactivator of transcription 1/2(STAT1/2),whereas it upregulates the phosphorylation and ubiquitination of type I IFN receptors(IFNARa/b).Thus,our results showthat HBV uses a novelmechanismto hijack cellular factors and signal cascades in order to evade host antiviral immunity and maintain persistent infection.We also demonstrate that CTHRC1 has a novel role in viral infection.展开更多
基金Supported by National Natural Science Foundation of China,No.30660225 and No.30960511
文摘AIM:To investigate the in vivo hepatoprotective effects and mechanisms of Gentiana manshurica Kitagawa (GM) in acetaminophen (APAP)-induced liver injury in mice.METHODS: GM (200, 150 or 50 mg/kg body weight) or N-acetyl-L-cysteine (NAC; 300 mg/kg body weight) was administrated orally with a single dose 2 h prior to APAP (300 mg/kg body weight) injection in mice.RESULTS: APAP treatment significantly depleted hepatic glutathione (GSH), increased serum aspartate aminot ransferase (AST), alanine aminotransferase (ALT) and malonyldialdehyde (MDA) and 4-hydroxynonenal levels, and decreased hepatic activity of glutathione peroxidase (GSH-px) and superoxide dismutase (SOD). However, the pretreatment of GM signif icantly alleviated APAP-induced oxidative stress by increasing GSH content, decreasing serum ALT, AST and MDA, and retaining the activity of GSH-px and SOD in the liver. Furthermore, GM pretreatment can inhibit caspase-3 activation and phosphorylation of c-Jun-NH2-terminal protein kinase 2 (JNK1/2) and extracellular signalregulated kinase (ERK). GM also remarkably attenuated hepatocyte apoptosis confirmed by the terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling method.CONCLUSION: Hepatoprotective effects of GM against APAP-induced acute toxicity are mediated either by preventing the decline of hepatic antioxidant status or its direct anti-apoptosis capacity. These results support that GM is a potent hepatoprotective agent.
基金supported by research grants from theMajor State Basic ResearchDevelopment Program(973 Program)(grant number 2012CB518900)the National Natural Science Foundation of China(grant numbers 31230005,31270206,31200134,and 81171525)+1 种基金the National Mega Project on Major Infectious Disease Prevention(grant numbers 2012ZX10002006-003 and 2012ZX10004-207)the Chinese Foundation for Hepatitis Prevention and Control(grant number CFHPC20132153).
文摘HepatitisBvirus(HBV)infection causes acuteand chronic liver diseases,but is not directly cytopathic.Liver injury results fromrepeated attempts of the cellular immune response system to control the viral infection.Here,we investigate the roles of cellular factors and signaling pathways involved in the regulation of HBV replication to reveal the mechanism underlying HBV infection and pathogenesis.Weshowthat collagen triple helix repeat containing 1(CTHRC1)expression is elevated in HBV-infected patients andin HBV-transfected cells through epigenetic modification and transcriptional regulation.CTHRC1 facilitates HBV replication in cultured cells and BALB/c mice by activating the PKCa/ERK/JNK/c-Jun cascade to repress the IFN/JAK/STAT pathway.HBV-activated CTHRC1 downregulates the activityof typeI interferon(IFN),theproductionof IFN-stimulatedgenes(ISGs),andthephosphorylationofsignal transducerandactivator of transcription 1/2(STAT1/2),whereas it upregulates the phosphorylation and ubiquitination of type I IFN receptors(IFNARa/b).Thus,our results showthat HBV uses a novelmechanismto hijack cellular factors and signal cascades in order to evade host antiviral immunity and maintain persistent infection.We also demonstrate that CTHRC1 has a novel role in viral infection.
