Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2023; 29(45): 5988-6016
Published online Dec 7, 2023. doi: 10.3748/wjg.v29.i45.5988
Pien Tze Huang alleviates Concanavalin A-induced autoimmune hepatitis by regulating intestinal microbiota and memory regulatory T cells
Xin Zeng, Miao-Hua Liu, Yi Xiong, Lin-Xin Zheng, Kai-En Guo, Hai-Mei Zhao, Yu-Ting Yin, Duan-Yong Liu, Bu-Gao Zhou
Xin Zeng, Miao-Hua Liu, Yi Xiong, Lin-Xin Zheng, Kai-En Guo, Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Hai-Mei Zhao, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Yu-Ting Yin, College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Duan-Yong Liu, Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Bu-Gao Zhou, Office of Academic Research, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Author contributions: Zeng X and Liu MH contributed to methodology, visualization, and validation of this study; Zeng X, Liu MH, Xiong Y, Zheng LX, and Guo KE were involved in the investigation of this manuscript; Xiong Y, Yin YT, Liu DY, and Zhou BG participated in the supervision of this manuscript; Xiong Y, Zhao HM, Yin YT, Liu DY, and Zhou BG contributed to the project administration and funding acquisition; Zhou BG and Yin YT contributed equally to this work as co-corresponding authors to collectively design, perform, analyze and complete the study and the paper, and to contribute efforts of equal substance throughout the research process.
Supported by the National Natural Science Foundation of China, No. 81603402, 82060798 and 81860791; the Special Fund Project for Graduate Innovation of Jiangxi University of Chinese Medicine, No. JZYC22S77; a Special Fund Project for Graduate Innovation of Jiangxi Province, No. YC2022-s840 and YC2022-B188; Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program, No. CXTD22008; the Young and Middle-aged Backbone Talent Project of Jiangxi Administration of Traditional Chinese Medicine, No. [2020]05; and Young Qhuang Scholars support Project of National Administration of Traditional Chinese Medicine, No. [2022]256.
Institutional animal care and use committee statement: All experiments on animals (including the euthanasia of mice) were performed in accordance with the Institutional Animal Care and Use Committee’s guidelines (Nanchang, China). The experimental protocols (Permit Number: JZLLSC20210090) were approved by The Jiangxi University of Chinese Medicine’s Animal Care and Use Committee.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bu-Gao Zhou, PhD, Professor, Office of Academic Research, Jiangxi University of Chinese Medicine, No. 1688 Meiling Road, Nanchang 330004, Jiangxi Province, China. 57161998@qq.com
Received: September 6, 2023
Peer-review started: September 6, 2023
First decision: September 23, 2023
Revised: September 26, 2023
Accepted: October 23, 2023
Article in press: October 23, 2023
Published online: December 7, 2023
Processing time: 85 Days and 22.7 Hours
ARTICLE HIGHLIGHTS
Research background

Autoimmune hepatitis (AIH) is a common and frequently-occurring interfacial hepatitis, and its etiology remains unknown. The interaction between regulatory T (Treg) cells and intestinal microbiota may provide a feasible therapeutic strategy for AIH.

Research motivation

As a well-known traditional Chinese medicine, Pien Tze Huang (PTH) is regularly used to treat liver conditions, including AIH. PTH has a physiological basis for controlling Treg cells and intestinal microbiota. However, it is unknown whether PTH can regulate intestinal microbiota and memory Treg (mTreg) cells to treat AIH.

Research objectives

To explore the mechanism of PTH treated AIH by determining the changes in the structure of intestinal microbiota and the level of mTreg cells.

Research methods

Following establishment of the mouse model of Concanavalin A (Con A)-induced AIH, prophylactic administration of PTH was given for 10 d. The levels of mTreg cells were measured by flow cytometry, and intestinal microbiota was analyzed by 16S rDNA analysis, while western blotting was used to identify the activation of the Toll-like receptor (TLR)2, TLR4/nuclear factor-κB (NF-κB), and CXCL16/CXCR6 signaling pathways.

Research results

In the present study, after PTH administration in mice with AIH, the expression of pro-inflammatory factors [such as tumor necrosis factor-alpha, interferon-γ, interleukin (IL)-1β, IL-2, IL-6, and IL-21] and Th17 cells was decreased, followed by improved pathological liver injury. In addition, the number of Treg/mTreg cells and IL-10 level were markedly increased, and the diversity of intestinal microbiota was regulated. Furthermore, activation of the TLR4/NF-κB, CXCL16/CXCR6 signaling pathway was suppressed in hepatic tissue.

Research conclusions

PTH effectively relieved pathological liver injury in mice with Con A-induced AIH, which was realized by improving intestinal microbiota balance and mTreg levels, and inhibiting the TLR/CXCL16/CXCR6/NF-κB signaling pathway.

Research perspectives

This research indicated that the mechanism of PTH treated mice with AIH was closely related to the regulation of intestinal microbiota balance and improving mTreg cell levels. These results provide scientific evidence for the application of PTH in AIH treatment and for the development of new drugs for AIH.