AIM To evaluate the immunomodulatory effect of oral administration of PRX-106 in the high-fat diet model.METHODS For 22 wk, C57BL/6 HFD-fed mice received daily oral treatments with BY-2 cells expressing recombinant an...AIM To evaluate the immunomodulatory effect of oral administration of PRX-106 in the high-fat diet model.METHODS For 22 wk, C57BL/6 HFD-fed mice received daily oral treatments with BY-2 cells expressing recombinant antitumor necrosis factor alpha fusion protein(PRX-106). Mice were followed for serum liver enzyme and triglyceride levels, liver histology and intrahepatic and systemic FACS.RESULTS The orally administered non-absorbable PRX-106 w a s b i o l o g i c a l l y a c t i v e. A l t e r e d d i s t r i b u t i o n o f CD4+CD25+Fox P3+ between the liver and spleen and an increase in the intrasplenic-to-intrahepatic CD4+CD25+Fox P3+ ratio and a decrease in the intrasplenic-to-intrahepatic CD8+CD25+Fox P3+ ratio were observed. An increase in intrahepatic NKT cells and a decrease in the intrasplenic-to-intrahepatic NKT ratio were noted. Assessment of the CD4-to-CD8 ratios showed sequestration of CD8+ lymphocytes in the liver. These effects were associated with a decrease in serum triglyceride levels, decrease in the aspartate aminotransferase levels, serum glucose levels, and HOMA-IR score. A decrease in hepatic triglycerides content was observed in the high dose-treated mice.CONCLUSION Orally administered PRX-106 shows biological activity and exerts an immunomodulatory effect, alleviating liver damage. The data suggest that PRX-106 may provide an oral immunotherapy for nonalcoholic steatohepatitis.展开更多
OBJECTIVE:To investigate the effects of Zhi Zi(Fructus Gardeniae) on non-alcoholic fatty liver disease(NAFLD) induced by a high-fat diet in the rat.METHODS:A rat model of NAFLD was established using a high-fat diet.Tw...OBJECTIVE:To investigate the effects of Zhi Zi(Fructus Gardeniae) on non-alcoholic fatty liver disease(NAFLD) induced by a high-fat diet in the rat.METHODS:A rat model of NAFLD was established using a high-fat diet.Twenty one rats were randomly divided into a normal group,a model group and a Zhi Zi treatment group,7 rats per group.Drinking water and the drug were intragastrically administrated for 5 weeks.Samples were then taken to observe pathological changes of the liver tissue(HE staining);changes in the fat metabolism pathway e.g.triglyceride(TG) and free fatty acid(FFA) content;alterations in liver function,i.e.serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) activity;and differences in tumor necrosis factor α(TNF-α) and P-IkB protein expression in the liver tissue.RESULTS:Fatty degeneration and vacuole-like changes of different degrees occurred in hepatic cells of the model group.Markers for fat metabolism,serum ALT and AST activities,and expressionof TNF-α and P-IkB proteins in liver tissue significantly increased.Fat metabolism in the Zhi Zi group significantly reduced,as shown by a drop in marker levels.Serum ALT and AST activities,and expression of TNF-α,P-IkB proteins in liver tissue were also significantly decreased in this group.CONCLUSION:Zhi Zi has a very strong inhibitory action on lipidosis and inflammatory injury in the rat model of NAFLD.This mechanism may possibly be related to the inhibition of the free fatty acid metabolism pathway.展开更多
基金Supported by Protalix Biotherapeutics and The Roman-Epstein Liver Research Foundation(in part)
文摘AIM To evaluate the immunomodulatory effect of oral administration of PRX-106 in the high-fat diet model.METHODS For 22 wk, C57BL/6 HFD-fed mice received daily oral treatments with BY-2 cells expressing recombinant antitumor necrosis factor alpha fusion protein(PRX-106). Mice were followed for serum liver enzyme and triglyceride levels, liver histology and intrahepatic and systemic FACS.RESULTS The orally administered non-absorbable PRX-106 w a s b i o l o g i c a l l y a c t i v e. A l t e r e d d i s t r i b u t i o n o f CD4+CD25+Fox P3+ between the liver and spleen and an increase in the intrasplenic-to-intrahepatic CD4+CD25+Fox P3+ ratio and a decrease in the intrasplenic-to-intrahepatic CD8+CD25+Fox P3+ ratio were observed. An increase in intrahepatic NKT cells and a decrease in the intrasplenic-to-intrahepatic NKT ratio were noted. Assessment of the CD4-to-CD8 ratios showed sequestration of CD8+ lymphocytes in the liver. These effects were associated with a decrease in serum triglyceride levels, decrease in the aspartate aminotransferase levels, serum glucose levels, and HOMA-IR score. A decrease in hepatic triglycerides content was observed in the high dose-treated mice.CONCLUSION Orally administered PRX-106 shows biological activity and exerts an immunomodulatory effect, alleviating liver damage. The data suggest that PRX-106 may provide an oral immunotherapy for nonalcoholic steatohepatitis.
基金Supported by Xiamen City Key Science and Technique Plan,NO.3502Z20100006Xiamen University's Student Experimental Plan for New Ideas,NO.XDDC 2011090
文摘OBJECTIVE:To investigate the effects of Zhi Zi(Fructus Gardeniae) on non-alcoholic fatty liver disease(NAFLD) induced by a high-fat diet in the rat.METHODS:A rat model of NAFLD was established using a high-fat diet.Twenty one rats were randomly divided into a normal group,a model group and a Zhi Zi treatment group,7 rats per group.Drinking water and the drug were intragastrically administrated for 5 weeks.Samples were then taken to observe pathological changes of the liver tissue(HE staining);changes in the fat metabolism pathway e.g.triglyceride(TG) and free fatty acid(FFA) content;alterations in liver function,i.e.serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) activity;and differences in tumor necrosis factor α(TNF-α) and P-IkB protein expression in the liver tissue.RESULTS:Fatty degeneration and vacuole-like changes of different degrees occurred in hepatic cells of the model group.Markers for fat metabolism,serum ALT and AST activities,and expressionof TNF-α and P-IkB proteins in liver tissue significantly increased.Fat metabolism in the Zhi Zi group significantly reduced,as shown by a drop in marker levels.Serum ALT and AST activities,and expression of TNF-α,P-IkB proteins in liver tissue were also significantly decreased in this group.CONCLUSION:Zhi Zi has a very strong inhibitory action on lipidosis and inflammatory injury in the rat model of NAFLD.This mechanism may possibly be related to the inhibition of the free fatty acid metabolism pathway.
