Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2023; 29(36): 5226-5239
Published online Sep 28, 2023. doi: 10.3748/wjg.v29.i36.5226
Curcumin alleviated dextran sulfate sodium-induced colitis by recovering memory Th/Tfh subset balance
Lin-Xin Zheng, Kai-En Guo, Jia-Qi Huang, Miao-Hua Liu, Bai-Ling Deng, Duan-Yong Liu, Bu-Gao Zhou, Wen Zhou, You-Bao Zhong, Hai-Mei Zhao
Lin-Xin Zheng, Kai-En Guo, Jia-Qi Huang, Miao-Hua Liu, Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Bai-Ling Deng, Hai-Mei Zhao, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Duan-Yong Liu, Bu-Gao Zhou, Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Wen Zhou, Nanchang Medical College, Nanchang 330052, Jiangxi Province, China
You-Bao Zhong, Laboratory Animal Research Center for Science and Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Author contributions: Zheng LX, Guo KE, Huang JQ, Liu MH, Deng BL, Liu DY, and Zhou BG performed the experiments; Zhou W and Zhao HM contributed reagents/materials/analytical tools; Zhao HM, Liu DY, and Zhong YB analyzed the data; Zheng LX, Guo KE, and Zhong YB wrote the paper; Zhou W, Zhong YB, and Zhao HM designed the experiments.
Supported by the National Natural Science Foundation of China, No. 81760808 and No. 82260863; Scientific and Technological Project of Education Department of Jiangxi Province, No. GJJ181582; Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program, No. CXTD22008; and Key Laboratory of Pharmacodynamics and Quality Evaluation on anti-Inflammatory Chinese Herbs, Jiangxi Administration of Traditional Chinese Medicine, No. 202208.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Experimental Animal Science and Technology Center of Jiangxi University of Traditional Chinese Medicine (Approval No. JZLLSC2021-196).
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: The data presented in this study are available from the corresponding author upon reasonable request.
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: Wen Zhou, MD, Associate Professor, Nanchang Medical College, No. 689 Huiren Road, Nanchang 330052, Jiangxi Province, China. zw1103380809@163.com
Received: August 16, 2023
Peer-review started: August 16, 2023
First decision: August 25, 2023
Revised: August 26, 2023
Accepted: September 7, 2023
Article in press: September 7, 2023
Published online: September 28, 2023
Abstract
BACKGROUND

Restoration of immune homeostasis by targeting the balance between memory T helper (mTh) cells and memory follicular T helper (mTfh) cells is a potential therapeutic strategy against ulcerative colitis (UC). Because of its anti-inflammatory and immunomodulatory properties, curcumin (Cur) is a promising drug for UC treatment. However, fewer studies have demonstrated whether Cur can modulate the mTh/mTfh subset balance in mice with colitis.

AIM

To explore the potential mechanism underlying Cur-mediated alleviation of colitis induced by dextran sulfate sodium (DSS) in mice by regulating the mTh and mTfh immune homeostasis.

METHODS

Balb/c mice were administered 3% and 2% DSS to establish the UC model and treated with Cur (200 mg/kg/d) by gavage on days 11-17. On the 18th d, all mice were anesthetized and euthanized, and the colonic length, colonic weight, and colonic weight index were evaluated. Histomorphological changes in the mouse colon were observed through hematoxylin-eosin staining. Levels of Th/mTh and Tfh/mTfh cell subsets in the spleen were detected through flow cytometry. Western blotting was performed to detect SOCS-1, SOCS-3, STAT3, p-STAT3, JAK1, p-JAK1, and NF-κB p65 protein expression levels in colon tissues.

RESULTS

Cur effectively mitigates DSS-induced colitis, facilitates the restoration of mouse weight and colonic length, and diminishes the colonic weight and colonic weight index. Simultaneously, it hinders ulcer development and inflammatory cell infiltration in the colonic mucous membrane. While the percentage of Th1, mTh1, Th7, mTh7, Th17, mTh17, Tfh1, mTfh1, Tfh7, mTfh7, Tfh17, and mTfh17 cells decreased after Cur treatment of the mice for 7 d, and the frequency of mTh10, Th10, mTfh10, and Tfh10 cells in the mouse spleen increased. Further studies revealed that Cur administration prominently decreased the SOCS-1, SOCS-3, STAT3, p-STAT3, JAK1, p-JAK1, and NF-κB p65 protein expression levels in the colon tissue.

CONCLUSION

Cur regulated the mTh/mTfh cell homeostasis to reduce DSS-induced colonic pathological damage, potentially by suppressing the JAK1/STAT3/SOCS signaling pathway.

Keywords: Curcumin, Ulcerative colitis, Memory T helper, Memory follicular T helper, JAK1/STAT3/SOCS

Core Tip: Memory T cells (mTh) are formed by the differentiation of initial T cells following antigenic stimulation and have a long lifespan. The dysfunction and out-of-balance of mTh and their subsets destroy immune homeostasis to induce autoimmune diseases including inflammatory bowel disease. Finding new drugs for inflammatory bowel disease (IBD) treatment from natural plant medicine and traditional Chinese medicine is a research hotspot. Cur can regulate memory B cells and other immune cells to effectively treat experimental colitis. However, whether Cur can regulate mTh cell- and mfTh cell-mediated homeostasis to treat IBD remains unclear. We here indicated that Cur regulates the mTh/memory follicular T helper cell homeostasis to reduce dextran sulfate sodium-induced colonic pathological injury, which may be achieved by inhibiting the JAK1/STAT3/SOCS signaling pathway.