Qiu YT, Luo XY, Deng YF, Zheng X, Qiu JG, Zhang LS, Huang XQ, Zheng XB, Huang HY. Modified Pulsatilla decoction alleviates 5-fluorouracil-induced intestinal mucositis by modulating the TLR4/MyD88/NF-κB pathway and gut microbiota. World J Gastroenterol 2025; 31(7): 98806 [DOI: 10.3748/wjg.v31.i7.98806]
Corresponding Author of This Article
Hai-Yang Huang, PhD, Associate Researcher, Dongguan Hospital of Guangzhou University of Chinese Medicine, No. 3 Songshan Lake Avenue, Dongcheng District, Dongguan 523000, Guangdong Province, China. 514234458@qq.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Yi-Tong Qiu, Xin-Yi Luo, Ya-Feng Deng, Xue Zheng, Jian-Guo Qiu, Lin-Sheng Zhang, Xiao-Qi Huang, Xue-Bao Zheng, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 525000, Guangdong Province, China
Xin-Yi Luo, Xue Zheng, Xiao-Qi Huang, Xue-Bao Zheng, Druggability Research Team, Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan 523808, Guangdong Province, China
Jian-Guo Qiu, Hai-Yang Huang, Institute of Traditional Chinese Medicine, Dongguan Hospital of Traditional Chinese Medicine, Dongguan 523000, Guangdong Province, China
Co-corresponding authors: Xue-Bao Zheng and Hai-Yang Huang.
Author contributions: Qiu YT designed and performed the experiments, acquired data and wrote the manuscript; Luo XY, Deng YF and Zhang LS analyzed and interpreted the data; Qiu YT, Zheng X, Qiu JG and Huang XQ reviewed and edited the manuscript; Zheng XB and Huang HY conceived the study and provided administrative support; Zheng XB and Huang HY have made equal and significant contributions to the conception, design, data analysis, and manuscript preparation of this study; all authors have read and approved the final manuscript.
Supported by Basic and Applied Basic Research Foundation of Guangdong Province, No. 2021B1515140043, No. 2022A1515140124 and No. 2023A1515140115.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Guangzhou University of Chinese Medicine (Protocol No. ZYD-2023-070).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
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: Hai-Yang Huang, PhD, Associate Researcher, Dongguan Hospital of Guangzhou University of Chinese Medicine, No. 3 Songshan Lake Avenue, Dongcheng District, Dongguan 523000, Guangdong Province, China. 514234458@qq.com
Received: July 6, 2024 Revised: November 19, 2024 Accepted: December 25, 2024 Published online: February 21, 2025 Processing time: 198 Days and 2.6 Hours
Abstract
BACKGROUND
Modified Pulsatilla decoction (PD), a PD with licorice and ejiao, is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis (IM) induced by tumor therapy. However, its specific molecular and biological mechanisms remain unclear.
AIM
To investigate the therapeutic effect and mechanism of modified PD in IM.
METHODS
This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD (3, 6, and 12 g/kg) in IM. The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry. Body weight loss, diarrhea scores, intestinal length, histopathological scores, and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM. Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis. The intestinal microbiota was characterized using Illumina NovaSeq sequencing.
RESULTS
The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice. Mechanistically, modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species, lipopolysaccharides, and pro-inflammatory cytokines (IL-1β, TNF-α, IFN-γ, IL-6, IL-8, and IL-17), while increasing the expression of the anti-inflammatory cytokine IL-10. Furthermore, modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins (occludin-1, claudin-1, and ZO-1) and mucin-2. Finally, 16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.
CONCLUSION
Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.
Core Tip: Developing safe and effective drugs for the treatment of intestinal mucositis (IM) is of great significance because IM is a common and severe complication of chemotherapy that can lead to a spectrum of gastrointestinal toxicities and even death. In this study, modified Pulsatilla decoction (PD) demonstrated significant efficacy in alleviating 5-fluorouracil-induced IM in mice. The treatment significantly improved key clinical symptoms, including weight loss, diarrhea, and intestinal damage, through modulation of the TLR4/MyD88/NF-κB pathway and restoration of intestinal microbiota balance. These findings provide a novel scientific foundation for the potential clinical application of modified PD in IM management.
