Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2015; 21(24): 7443-7456
Published online Jun 28, 2015. doi: 10.3748/wjg.v21.i24.7443
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
Tawfik Khoury, Ami Ben Ya'acov, Yehudit Shabat, Lidya Zolotarovya, Ram Snir, Yaron Ilan
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
Author contributions: Khoury T and Ben Ya'acov A contributed equally to this work; Khoury T, Ben Ya'acov A, Shabat Y and Zolotarovya L conducted the experiments and summarized the data; Khoury T, Ben Ya'acov A, Snir R and Ilan Y prepared the manuscript.
Supported by Grants from The Roaman-Epstein Liver Research Foundation (partly, to Ilan Y).
Institutional animal care and use committee: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use committee of the Hebrew University Hadassah Medical Center (IACUC protocol number: MD-13-13733-3).
Conflict-of-interest: The authors declare no conflicting interest.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Tawfik Khoury, MD, Gastroeneterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, PO Box 12000, Jerusalem IL-91120, Israel. tawfikkhoury1@hotmail.com
Telephone: +972-2-6777816 Fax: +972-2-6431021
Received: November 11, 2014
Peer-review started: November 12, 2014
First decision: January 8, 2015
Revised: February 8, 2015
Accepted: March 30, 2015
Article in press: March 31, 2015
Published online: June 28, 2015
Processing time: 230 Days and 13.3 Hours
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Non-alcoholic steatohepatitis; Fatty liver; Regulatory T cells; Soy; Type 2 diabetes; ConA hepatitis

Core tip: 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. Oral administration of these extracts had an additive effect in alleviating concanavalin A hepatitis and ameliorated liver injury in the high fat diet model of non-alcoholic steatohepatitis, and in the methionine and choline reduced diet combined with the high fat diet model. The effects were associated with reduced serum tumor necrosis factor alpha and alteration of regulatory T cell distribution.