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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation
Dong-Xue Lu, Feng Liu, Hua Wu, Hai-Xia Liu, Bing-Yu Chen, Jing Yan, Yin Lu, Zhi-Guang Sun
Dong-Xue Lu, Hua Wu, Department of Nutrition, Acupuncture and Moxibustion and Massage College & Health Preservation and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Feng Liu, Department of Orthopaedics, Nanjing Pukou District Chinese Medicine Hospital, Nanjing 210000, Jiangsu Province, China
Hai-Xia Liu, Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
Bing-Yu Chen, Department of Geriatrics, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 451150, Henan Province, China
Jing Yan, Key Laboratory for Metabolic Diseases in Chinese Medicine, The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Yin Lu, Key Pharmacology Laboratory of Jiangsu Province, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Zhi-Guang Sun, The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Author contributions: Lu DX and Liu F contributed to the study design, data analysis and interpretation, and writing of the manuscript; Yan J contributed to the study design, data analysis, and drafting of the manuscript; Lu Y, Chen BY, Liu HX, and Wu H were responsible for data collection and analysis.
Supported by the National Natural Science Foundation of China, No. 81673795.
Institutional animal care and use committee statement: All animal experiments were approved by Animal Experimental Ethics Committee of Nanjing University of Chinese Medicine (No. 202006A022).
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: Zhi-Guang Sun, PhD, Chief Doctor, Professor, The First Clinical Medical College, Nanjing University of Chinese Medicine, No. 138, Xianlin Avenue, Qixia District, Nanjing 210023, Jiangsu Province, China. 110399@njucm.edu.cn
Received: September 14, 2021
Peer-review started: September 14, 2021
First decision: December 27, 2021
Revised: January 5, 2022
Accepted: July 18, 2022
Article in press: July 18, 2022
Published online: August 28, 2022
BACKGROUND
Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients. However, they can also damage normal cells and cause serious intestinal toxicity, leading to gastrointestinal mucositis[1]. Traditional Chinese medicine is effective in improving the side effects of chemotherapy. Wumei pills (WMP) was originally documented in the Treatise on Exogenous Febrile Diseases. It has a significant effect on chronic diarrhea and other gastrointestinal diseases, but it is not clear whether it affects chemotherapy-induced intestinal mucositis (CIM).
AIM
To explore the potential mechanism of WMP in the treatment of CIM through experimental research.
METHODS
We used an intraperitoneal injection of 5-fluorouracil (5-Fu) to establish a CIM mouse model and an oral gavage of WMP decoction (11325 and 22650 mg/kg) to evaluate the efficacy of WMP in CIM. We evaluated the effect of WMP on CIM by observing the general conditions of the mice (body weight, food intake, spleen weight, diarrhea score, and hematoxylin and eosin stained tissues). The expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and myeloperoxidase (MPO), as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway proteins and tight junction proteins (zonula occludens-1, claudin-1, E-cadherin, and mucin-2) was determined. Furthermore, intestinal permeability, intestinal flora, and the levels of short-chain fatty acids (SCFA) were also assessed.
RESULTS
WMP effectively improved the body weight, spleen weight, food intake, diarrhea score, and inflammatory status of the mice with intestinal mucositis, which preliminarily confirmed the efficacy of WMP in CIM. Further experiments showed that in addition to reducing the levels of TNF-α, IL-1β, IL-6, and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins, WMP also repaired the integrity of the mucosal barrier of mice, regulated the intestinal flora, and increased the levels of SCFA (such as butyric acid).
CONCLUSION
WMP can play a therapeutic role in CIM by alleviating inflammation, restoring the mucosal barrier, and regulating gut microbiota.
Core Tip: In this study, the compound Wumei pills was selected as the representative of the traditional Chinese medicine compound, and it was clarified that the compatibility of the compound medicines may also regulate the intestinal flora, which is instructive for the study of the onset mode and mechanism of the Chinese medicine compound. The results obtained will provide a scientific basis for finding clinical potential treatment and intervention strategies for chemotherapy-induced intestinal mucositis.
