Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2024; 16(10): 4209-4231
Published online Oct 15, 2024. doi: 10.4251/wjgo.v16.i10.4209
Jianpi-Huatan-Huoxue-Anshen formula ameliorates gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with H22 hepatocellular carcinoma
Ya-Nan Wang, Xiang-Yang Zhai, Zheng Wang, Chun-Ling Gao, Sui-Cai Mi, Wen-Li Tang, Xue-Min Fu, Huai-Bang Li, Li-Feng Yue, Peng-Fei Li, Sheng-Yan Xi
Ya-Nan Wang, Zheng Wang, Wen-Li Tang, Xue-Min Fu, Huai-Bang Li, Peng-Fei Li, Sheng-Yan Xi, Department of TCM, Xiang’an Hospital, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China
Xiang-Yang Zhai, Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China
Chun-Ling Gao, Department of Radiotherapy, Chenggong Hospital of Xiamen University, PLA 73rd Army Hospital, Xiamen 361003, Fujian Province, China
Sui-Cai Mi, Department of Oncology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361015, Fujian Province, China
Li-Feng Yue, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
Author contributions: Wang YN was responsible for methodology, data curation, and writing of the original draft; Zhai XY was responsible for methodology and validation; Wang Z was responsible for methodology and data curation; Gao CL, Mi CS, Tang WL, Fu XM, and Li HB were responsible for methodology; Yue LF was responsible for manuscript review & editing; Li PF was responsible for project administration; Xi SY was responsible for manuscript review & editing, funding acquisition, supervision, and project administration; all authors have read and agreed to the published version of the manuscript.
Supported by Natural Science Foundation of Xiamen, China, No. 3502Z20227171; the Young Investigator Research Program of Xiang’an Hospital of Xiamen University, No. XAH23005; the Traditional Chinese Medicine Foundation of Xiamen, No. XWZY-2023-0103; Natural Science Foundation of Fujian, China, No. 2018J01136; and National Natural Science Foundation of China, No. 81202659.
Institutional animal care and use committee statement: All experimental steps of this experiment have been approved by the Animal Management Ethics Committee of Xiamen University (XMULAC-20170018).
Conflict-of-interest statement: The authors declare that there are no known competing financial interests or personal relationships among all authors of this article that could influence all studies reported in this article.
Data sharing statement: The data of this study are available from the corresponding author or any co-author on 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: Sheng-Yan Xi, Doctor, PhD, Associate Chief Physician, Associate Professor, Department of TCM, Xiang’an Hospital, School of Medicine, Xiamen University, No. 4221-122 Xiang’an Nan Road, Xiamen 361102, Fujian Province, China. xishengyan@xmu.edu.cn
Received: April 7, 2024
Revised: August 6, 2024
Accepted: September 3, 2024
Published online: October 15, 2024
Processing time: 172 Days and 7.2 Hours
Abstract
BACKGROUND

Jianpi-Huatan-Huoxue-Anshen formula [Tzu-Chi cancer-antagonizing & life-protecting II decoction (TCCL)] is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life. However, its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear.

AIM

To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma (HCC).

METHODS

Ninety-six mice were inoculated subcutaneously with HCC cells. One week later, the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model. Thirty-six mice were randomly selected before administration, and feces, ileal tissue, and ileal contents were collected from each mouse. The remaining mice were randomized into normal saline, continuous chemotherapy, Yangzheng Xiaoji capsules-treated, and three TCCL-treated groups. After treatment, feces, tumors, liver, spleen, thymus, stomach, jejunum, ileum, and colon tissues, and ileal contents were collected. Morphological changes, serum levels of IL-1β, IL-6, IL-8, IL-10, IL-22, TNF-α, and TGF-β, intestinal SIgA, and protein and mRNA expression of ZO-1, NF-κB, Occludin, MUC-2, Claudin-1, and IκB-α in colon tissues were documented. The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing.

RESULTS

TCCL treatment improved thymus and spleen weight, thymus and spleen indexes, and body weight, decreased tumor volumes and tumor tissue cell density, and alleviated injury to gastric, ileal, and colonic mucosal tissues. Among proteins and genes associated with inflammation, IL-10, TGF-β, SIgA, ZO-1, MUC-2, and Occludin were upregulated, whereas NF-κB, IL-1β, IL-6, TNF-α, IL-22, IL-8, and IκB-α were downregulated. Additionally, TCCL increased the proportions of fecal Actinobacteria, AF12, Adlercreutzia, Clostridium, Coriobacteriaceae, and Paraprevotella in the intermediate stage of treatment, decreased the proportions of Mucipirillum, Odoribacter, RF32, YS2, and Rikenellaceae but increased the proportions of p_Deferribacteres and Lactobacillus at the end of treatment. Studies on ileal mucosal microbiota showed similar findings. Moreover, TCCL improved community richness, evenness, and the diversity of fecal and ileal mucosal flora.

CONCLUSION

TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury, potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa, enhancing intestinal barrier function, and maintaining gastrointestinal microecological balance. Hence, TCCL is a very effective adjuvant to chemotherapy.

Keywords: Chinese medicine; Chemotherapy; H22 hepatocellular carcinoma; Intestinal barrier function; Intestinal microecological balance

Core Tip: Jianpi-Huatan-Huoxue-Anshen formula (Tzu-Chi cancer-antagonizing & life-protecting II decoction) down-regulates the NF-κB signaling pathway and the release of inflammatory factors, alleviates intestinal inflammation, improves intestinal morphology, reduces intestinal barrier damage, and maintains the dynamic balance of intestinal microecology. These results reveal the potential role and advantages of Chinese herbal compounds in improving the unbalanced microenvironment after cancer chemotherapy.