Ginsenoside F2 attenuates chronic-binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cells

Background: Recently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng, have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanis...

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Main Authors: Myung-Ho Kim, Hee-Hoon Kim, Jong-Min Jeong, Young-Ri Shim, Jun-Hee Lee, Ye Eun Kim, Tom Ryu, Keungmo Yang, Kyu-Rae Kim, Byeong-Min Jeon, Sun Chang Kim, Jae-Kwang Jung, Jae-Kap Choi, Young-Sun Lee, Jin-Seok Byun, Won-Il Jeong
Format: Article
Language:English
Published: Elsevier 2020-11-01
Series:Journal of Ginseng Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1226845320300609
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author Myung-Ho Kim
Hee-Hoon Kim
Jong-Min Jeong
Young-Ri Shim
Jun-Hee Lee
Ye Eun Kim
Tom Ryu
Keungmo Yang
Kyu-Rae Kim
Byeong-Min Jeon
Sun Chang Kim
Jae-Kwang Jung
Jae-Kap Choi
Young-Sun Lee
Jin-Seok Byun
Won-Il Jeong
author_facet Myung-Ho Kim
Hee-Hoon Kim
Jong-Min Jeong
Young-Ri Shim
Jun-Hee Lee
Ye Eun Kim
Tom Ryu
Keungmo Yang
Kyu-Rae Kim
Byeong-Min Jeon
Sun Chang Kim
Jae-Kwang Jung
Jae-Kap Choi
Young-Sun Lee
Jin-Seok Byun
Won-Il Jeong
author_sort Myung-Ho Kim
collection DOAJ
description Background: Recently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng, have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanism by which GF2 ameliorated alcoholic liver injury. Methods: To induce alcoholic liver injury, C57BL/6J wild type (WT) or interleukin (IL)-10 knockout (KO) mice were orally administered with ethanol (3 g/kg) or ethanol-containing GF2 (50 mg/kg) for 2 wk. Liver injury and infiltration of macrophages and neutrophils were evaluated by serum biochemistry and immunohistochemistry, respectively. The changes of hepatic immune cells were assessed by flow cytometry and polymerase chain reaction analysis. In vitro differentiation of naïve T cells was performed. Results: GF2 treatment significantly attenuated alcoholic liver injury, in which infiltrations of inflammatory macrophages and neutrophils were decreased. Moreover, the frequencies of Foxp3+ regulatory T cells (Tregs) increased but IL-17–producing T (Th17) cells decreased in GF2-treated mice compared to controls. Furthermore, the mRNA expression of IL-10 and Foxp3 was significantly increased, whereas IL-17 mRNA expression was suppressed in GF2-treated mice. However, these beneficial roles of GF2 were not observed in GF2-treated IL-10 KO mice, suggesting a critical role of IL-10. Similarly, GF2 treatment suppressed differentiation of naïve T cells into Th17 cells by inhibiting RORγt expression and stimulating Foxp3 expression. Conclusion: The present study suggests that GF2 treatment attenuates alcoholic liver injury by increasing IL-10 expression and Tregs and decreasing IL-17 expression and Th17 cells.
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spelling doaj.art-0722f267c7d34bc8b469e06aa6e49f052022-12-21T18:55:41ZengElsevierJournal of Ginseng Research1226-84532020-11-01446815822Ginsenoside F2 attenuates chronic-binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cellsMyung-Ho Kim0Hee-Hoon Kim1Jong-Min Jeong2Young-Ri Shim3Jun-Hee Lee4Ye Eun Kim5Tom Ryu6Keungmo Yang7Kyu-Rae Kim8Byeong-Min Jeon9Sun Chang Kim10Jae-Kwang Jung11Jae-Kap Choi12Young-Sun Lee13Jin-Seok Byun14Won-Il Jeong15Laboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaLaboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaLaboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaLaboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaLaboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaLaboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaLaboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaLaboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaLaboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; Intelligent Synthetic Biology Center, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaDepartment of Oral Medicine, School of Dentistry, Kyungpook National University, Daegu, Republic of KoreaDepartment of Oral Medicine, School of Dentistry, Kyungpook National University, Daegu, Republic of KoreaDepartment of Internal Medicine, Korea University College of Medicine, Seoul, Republic of KoreaDepartment of Oral Medicine, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea; Corresponding author. Department of Oral Medicine, School of Dentistry, Kyungpook National University, Daegu 41940, South Korea.Laboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; Corresponding author. Lab of Liver Research, Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, South Korea.Background: Recently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng, have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanism by which GF2 ameliorated alcoholic liver injury. Methods: To induce alcoholic liver injury, C57BL/6J wild type (WT) or interleukin (IL)-10 knockout (KO) mice were orally administered with ethanol (3 g/kg) or ethanol-containing GF2 (50 mg/kg) for 2 wk. Liver injury and infiltration of macrophages and neutrophils were evaluated by serum biochemistry and immunohistochemistry, respectively. The changes of hepatic immune cells were assessed by flow cytometry and polymerase chain reaction analysis. In vitro differentiation of naïve T cells was performed. Results: GF2 treatment significantly attenuated alcoholic liver injury, in which infiltrations of inflammatory macrophages and neutrophils were decreased. Moreover, the frequencies of Foxp3+ regulatory T cells (Tregs) increased but IL-17–producing T (Th17) cells decreased in GF2-treated mice compared to controls. Furthermore, the mRNA expression of IL-10 and Foxp3 was significantly increased, whereas IL-17 mRNA expression was suppressed in GF2-treated mice. However, these beneficial roles of GF2 were not observed in GF2-treated IL-10 KO mice, suggesting a critical role of IL-10. Similarly, GF2 treatment suppressed differentiation of naïve T cells into Th17 cells by inhibiting RORγt expression and stimulating Foxp3 expression. Conclusion: The present study suggests that GF2 treatment attenuates alcoholic liver injury by increasing IL-10 expression and Tregs and decreasing IL-17 expression and Th17 cells.http://www.sciencedirect.com/science/article/pii/S1226845320300609Interleukin-10Interleukin-17MacrophageNeutrophilPanax ginseng
spellingShingle Myung-Ho Kim
Hee-Hoon Kim
Jong-Min Jeong
Young-Ri Shim
Jun-Hee Lee
Ye Eun Kim
Tom Ryu
Keungmo Yang
Kyu-Rae Kim
Byeong-Min Jeon
Sun Chang Kim
Jae-Kwang Jung
Jae-Kap Choi
Young-Sun Lee
Jin-Seok Byun
Won-Il Jeong
Ginsenoside F2 attenuates chronic-binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cells
Journal of Ginseng Research
Interleukin-10
Interleukin-17
Macrophage
Neutrophil
Panax ginseng
title Ginsenoside F2 attenuates chronic-binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cells
title_full Ginsenoside F2 attenuates chronic-binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cells
title_fullStr Ginsenoside F2 attenuates chronic-binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cells
title_full_unstemmed Ginsenoside F2 attenuates chronic-binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cells
title_short Ginsenoside F2 attenuates chronic-binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cells
title_sort ginsenoside f2 attenuates chronic binge ethanol induced liver injury by increasing regulatory t cells and decreasing th17 cells
topic Interleukin-10
Interleukin-17
Macrophage
Neutrophil
Panax ginseng
url http://www.sciencedirect.com/science/article/pii/S1226845320300609
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