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
Abstract
BACKGROUND

Traditional Chinese medicine has used the drug Pien Tze Huang (PTH), a classic prescription, to treat autoimmune hepatitis (AIH). However, the precise mode of action is still unknown.

AIM

To investigate the mechanism of PTH in an AIH mouse model by determining the changes in gut microbiota structure and memory regulatory T (mTreg) cells functional levels.

METHODS

Following induction of the AIH mouse model induced by Concanavalin A (Con A), 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 rRNA analysis, while western blotting was used to identify activation of the toll-like receptor (TLR)2, TLR4/nuclear factor-κB (NF-κB), and CXCL16/CXCR6 signaling pathways.

RESULTS

In the liver of mice with AIH, PTH relieved the pathological damage and reduced the numbers of T helper type 17 cells and interferon-γ, tumor necrosis factor-alpha, interleukin (IL)-1β, IL-2, IL-6, and IL-21 expression. Simultaneously, PTH stimulated the abundance of helpful bacteria, promoted activation of the TLR2 signal, which may enhance Treg/mTreg cells quantity to produce IL-10, and suppressed activation of the TLR4/NF-κB and CXCL16/CXCR6 signaling pathways.

CONCLUSION

PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH, which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway.

Keywords: Pien Tze Huang; Autoimmune hepatitis; Intestinal microbiota; Memory regulatory T cell; Toll-like receptor signaling

Core Tip: Intestinal microbiota disorder plays an important role in the pathogenesis of autoimmune hepatitis (AIH), in which one of the main characteristics is the hypofunction of memory regulatory T (mTreg) cells to maintain immune tolerance. The interaction between Treg cells and intestinal microbiota may provide a feasible therapeutic strategy for AIH. As a well-known traditional Chinese medicine, Pien Tze Huang (PTH) can effectively treat AIH in the clinic. However, its mechanism is still unclear. In the present study, PTH regulated intestinal microbiota balance and restored mTreg cells to alleviate experimental AIH, which was closely related to the toll-like receptor/CXCL16/CXCR6/nuclear factor-κB signaling pathway.