Total glucosides of paeony decreases apoptosis of hepatocytes and inhibits maturation of dendritic cells in autoimmune hepatitis
Total glucosides of paeony (TGP), an active mixture extracted from paeony root, has anti-inflammatory and immunoregulatory effects and is widely used for the treatment of autoimmune diseases such as rheumatoid arthritis. However, the role of TGP in autoimmune hepatitis (AIH) is still unknown. In thi...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2020-04-01
|
Series: | Biomedicine & Pharmacotherapy |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332220301013 |
id |
doaj-a9a83f7b992647a18b06a1af9c678ba8 |
---|---|
record_format |
Article |
spelling |
doaj-a9a83f7b992647a18b06a1af9c678ba82021-05-20T07:40:37ZengElsevierBiomedicine & Pharmacotherapy0753-33222020-04-01124109911Total glucosides of paeony decreases apoptosis of hepatocytes and inhibits maturation of dendritic cells in autoimmune hepatitisMengyi Shen0Ruoting Men1Xiaoli Fan2Tingting Wang3Chen Huang4Haoran Wang5Tinghong Ye6Xuefeng Luo7Li Yang8Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Liver Surgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, China; Corresponding authors.Department of Gastroenterology and Hepatology, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, China; Corresponding authors.Total glucosides of paeony (TGP), an active mixture extracted from paeony root, has anti-inflammatory and immunoregulatory effects and is widely used for the treatment of autoimmune diseases such as rheumatoid arthritis. However, the role of TGP in autoimmune hepatitis (AIH) is still unknown. In this study, we aimed to investigate the effect of TGP in autoimmune liver disease (AILD) patients and in concanavalin A (Con A)-induced experimental autoimmune hepatitis (EAH). Changes in biochemical parameters of AILD patients showed that treatment with TGP exerts significant protective effects on liver function, as reflected by decreased levels of serum alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase and total bilirubin. In EAH mice, we found that pretreatment with TGP reduced the levels of serum liver enzyme levels, histopathological damage and hepatocyte apoptosis. Importantly, flow cytometry analysis showed that pretreatment with TGP reduced the infiltration of mature dendritic cells in the liver. In vitro, TGP pretreatment ameliorated the Con A-induced mitochondrial membrane potential decline, reactive oxygen species increase, and apoptosis increase in hepatocytes. In addition, the levels of Bax, Cleaved Caspase-3 and cytoplasmic Cytochrome C decreased during this process, whereas those of Bcl-2 and mitochondrial Cytochrome C increased. Therefore, TGP might decrease hepatocyte apoptosis through the mitochondrial apoptotic pathway. Moreover, the maturation of bone marrow dendritic cells was also inhibited by TGP treatment. In conclusion, TGP treatment ameliorates AIH by regulating hepatocyte apoptosis and DC maturation. TGP is a potential compound for AIH treatment.http://www.sciencedirect.com/science/article/pii/S0753332220301013Total glucosides of paeonyAutoimmune hepatitisDendritic cellsHepatocyte apoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mengyi Shen Ruoting Men Xiaoli Fan Tingting Wang Chen Huang Haoran Wang Tinghong Ye Xuefeng Luo Li Yang |
spellingShingle |
Mengyi Shen Ruoting Men Xiaoli Fan Tingting Wang Chen Huang Haoran Wang Tinghong Ye Xuefeng Luo Li Yang Total glucosides of paeony decreases apoptosis of hepatocytes and inhibits maturation of dendritic cells in autoimmune hepatitis Biomedicine & Pharmacotherapy Total glucosides of paeony Autoimmune hepatitis Dendritic cells Hepatocyte apoptosis |
author_facet |
Mengyi Shen Ruoting Men Xiaoli Fan Tingting Wang Chen Huang Haoran Wang Tinghong Ye Xuefeng Luo Li Yang |
author_sort |
Mengyi Shen |
title |
Total glucosides of paeony decreases apoptosis of hepatocytes and inhibits maturation of dendritic cells in autoimmune hepatitis |
title_short |
Total glucosides of paeony decreases apoptosis of hepatocytes and inhibits maturation of dendritic cells in autoimmune hepatitis |
title_full |
Total glucosides of paeony decreases apoptosis of hepatocytes and inhibits maturation of dendritic cells in autoimmune hepatitis |
title_fullStr |
Total glucosides of paeony decreases apoptosis of hepatocytes and inhibits maturation of dendritic cells in autoimmune hepatitis |
title_full_unstemmed |
Total glucosides of paeony decreases apoptosis of hepatocytes and inhibits maturation of dendritic cells in autoimmune hepatitis |
title_sort |
total glucosides of paeony decreases apoptosis of hepatocytes and inhibits maturation of dendritic cells in autoimmune hepatitis |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2020-04-01 |
description |
Total glucosides of paeony (TGP), an active mixture extracted from paeony root, has anti-inflammatory and immunoregulatory effects and is widely used for the treatment of autoimmune diseases such as rheumatoid arthritis. However, the role of TGP in autoimmune hepatitis (AIH) is still unknown. In this study, we aimed to investigate the effect of TGP in autoimmune liver disease (AILD) patients and in concanavalin A (Con A)-induced experimental autoimmune hepatitis (EAH). Changes in biochemical parameters of AILD patients showed that treatment with TGP exerts significant protective effects on liver function, as reflected by decreased levels of serum alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase and total bilirubin. In EAH mice, we found that pretreatment with TGP reduced the levels of serum liver enzyme levels, histopathological damage and hepatocyte apoptosis. Importantly, flow cytometry analysis showed that pretreatment with TGP reduced the infiltration of mature dendritic cells in the liver. In vitro, TGP pretreatment ameliorated the Con A-induced mitochondrial membrane potential decline, reactive oxygen species increase, and apoptosis increase in hepatocytes. In addition, the levels of Bax, Cleaved Caspase-3 and cytoplasmic Cytochrome C decreased during this process, whereas those of Bcl-2 and mitochondrial Cytochrome C increased. Therefore, TGP might decrease hepatocyte apoptosis through the mitochondrial apoptotic pathway. Moreover, the maturation of bone marrow dendritic cells was also inhibited by TGP treatment. In conclusion, TGP treatment ameliorates AIH by regulating hepatocyte apoptosis and DC maturation. TGP is a potential compound for AIH treatment. |
topic |
Total glucosides of paeony Autoimmune hepatitis Dendritic cells Hepatocyte apoptosis |
url |
http://www.sciencedirect.com/science/article/pii/S0753332220301013 |
work_keys_str_mv |
AT mengyishen totalglucosidesofpaeonydecreasesapoptosisofhepatocytesandinhibitsmaturationofdendriticcellsinautoimmunehepatitis AT ruotingmen totalglucosidesofpaeonydecreasesapoptosisofhepatocytesandinhibitsmaturationofdendriticcellsinautoimmunehepatitis AT xiaolifan totalglucosidesofpaeonydecreasesapoptosisofhepatocytesandinhibitsmaturationofdendriticcellsinautoimmunehepatitis AT tingtingwang totalglucosidesofpaeonydecreasesapoptosisofhepatocytesandinhibitsmaturationofdendriticcellsinautoimmunehepatitis AT chenhuang totalglucosidesofpaeonydecreasesapoptosisofhepatocytesandinhibitsmaturationofdendriticcellsinautoimmunehepatitis AT haoranwang totalglucosidesofpaeonydecreasesapoptosisofhepatocytesandinhibitsmaturationofdendriticcellsinautoimmunehepatitis AT tinghongye totalglucosidesofpaeonydecreasesapoptosisofhepatocytesandinhibitsmaturationofdendriticcellsinautoimmunehepatitis AT xuefengluo totalglucosidesofpaeonydecreasesapoptosisofhepatocytesandinhibitsmaturationofdendriticcellsinautoimmunehepatitis AT liyang totalglucosidesofpaeonydecreasesapoptosisofhepatocytesandinhibitsmaturationofdendriticcellsinautoimmunehepatitis |
_version_ |
1721435134495817728 |