title: Altered distribution of regulatory lymphocytes by oral administration of soy-extracts exerts a hepatoprotective effect alleviating immune mediated liver injury, non-alcoholic steatohepatitis and insulin resistance.
abstract: OBJECTIVE
  To determine the immune-modulatory and the hepatoprotective effects of oral administration of two soy extracts in immune mediated liver injury and non-alcoholic steatohepatitis (NASH).
  
  
  METHODS
  Two soy extracts, M1 and OS, were orally administered to mice with concanavalin A (ConA) immune-mediated hepatitis, to high-fat diet (HFD) mice and to methionine and choline reduced diet combined with HFD mice. Animals were followed for disease and immune biomarkers.
  
  
  RESULTS
  Oral administration of OS and M1 had an additive effect in alleviating ConA hepatitis manifested by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels. Oral administration of the OS and M1 soy derived fractions, ameliorated liver injury in the high fat diet model of NASH, manifested by a decrease in hepatic triglyceride levels, improvement in liver histology, decreased serum cholesterol and triglycerides and improved insulin resistance. In the methionine and choline reduced diet combined with the high fat diet model, we noted a decrease in hepatic triglycerides and improvement in blood glucose levels and liver histology. The effects were associated with reduced serum tumor necrosis factor alpha and alteration of regulatory T cell distribution.
  
  
  CONCLUSIONS
  Oral administration of the combination of OS and M1 soy derived extracts exerted an adjuvant effect in the gut-immune system, altering the distribution of regulatory T cells, and alleviating immune mediated liver injury, hyperlipidemia and insulin resistance.
authors.affiliation: Tawfik Khoury, Ami Ben Ya'acov, Yehudit Shabat, Lidya Zolotarovya, Ram Snir, Yaron Ilan, Gastroeneterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem IL-91120, Israel.
authors.forename: Tawfik
authors.initials: T
authors.lastname: Khoury
authors.affiliation: Tawfik Khoury, Ami Ben Ya'acov, Yehudit Shabat, Lidya Zolotarovya, Ram Snir, Yaron Ilan, Gastroeneterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem IL-91120, Israel.
authors.forename: Ami
authors.initials: A
authors.lastname: Ben Ya'acov
authors.affiliation: Tawfik Khoury, Ami Ben Ya'acov, Yehudit Shabat, Lidya Zolotarovya, Ram Snir, Yaron Ilan, Gastroeneterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem IL-91120, Israel.
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Shabat
authors.affiliation: Tawfik Khoury, Ami Ben Ya'acov, Yehudit Shabat, Lidya Zolotarovya, Ram Snir, Yaron Ilan, Gastroeneterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem IL-91120, Israel.
authors.forename: Lidya
authors.initials: L
authors.lastname: Zolotarovya
authors.affiliation: Tawfik Khoury, Ami Ben Ya'acov, Yehudit Shabat, Lidya Zolotarovya, Ram Snir, Yaron Ilan, Gastroeneterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem IL-91120, Israel.
authors.forename: Ram
authors.initials: R
authors.lastname: Snir
authors.affiliation: Tawfik Khoury, Ami Ben Ya'acov, Yehudit Shabat, Lidya Zolotarovya, Ram Snir, Yaron Ilan, Gastroeneterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem IL-91120, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Ilan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D002796:Choline Deficiency / Q000150:complications; D003208:Concanavalin A; D019610:Cytoprotection; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D024821:Metabolic Syndrome / Q000276:immunology / Q000517:prevention & control; D008715:Methionine / Q000172:deficiency; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D010936:Plant Extracts / Q000008:administration & dosage*; D013025:Glycine max; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007155:Immunologic Factors; D007328:Insulin; D008055:Lipids; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D008715:Methionine
keywords: ConA hepatitis; Fatty liver; Non-alcoholic steatohepatitis; Regulatory T cells; Soy; Type 2 diabetes