Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. May 27, 2025; 17(5): 106000
Published online May 27, 2025. doi: 10.4240/wjgs.v17.i5.106000
Huangqi decoction ameliorated intestinal barrier dysfunction via regulating NF-κB signaling pathway in slow transit constipation model mice
Hua-Xian Chen, Guo-Zhong Xiao, Chao-Xin Yang, Yi-Hui Zheng, Ming-Yuan Lei, Hao Xu, Dong-Lin Ren, Liang Huang, Qiu-Lan He, Hong-Cheng Lin
Hua-Xian Chen, Guo-Zhong Xiao, Chao-Xin Yang, Yi-Hui Zheng, Ming-Yuan Lei, Dong-Lin Ren, Liang Huang, Hong-Cheng Lin, Department of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Hao Xu, Department of Anorectal, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China
Qiu-Lan He, Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
Co-first authors: Hua-Xian Chen and Guo-Zhong Xiao.
Co-corresponding authors: Qiu-Lan He and Hong-Cheng Lin.
Author contributions: Chen HX, Ren DL, Huang L, He QL, and Lin HC designed the research study; Chen HX, Xiao GZ, Yang CX, Zheng YH, Lei MY, and Xu H performed the research; Chen HX, Xiao GZ, and Yang CX wrote the original draft; Zheng YH, Lei MY, Xu H, Ren DL, Huang L, He QL, and Lin HC reviewed and edited the manuscript; Chen HX and Lin HC acquired funding; Huang L, He QL, and Lin HC supervised the project; Chen HX and Xiao GZ contributed equally as co-first authors; He QL and Lin HC contributed equally as co-corresponding authors.
Supported by the Natural Science Foundation of Guangdong Province for Distinguished Young Scholars, No. 2022B1515020003; the National Natural Science Foundation of China, No. 82174369, No. 82405397, No. 82374442, and No. 81973847; Postdoctoral Fellowship Program of CPSF No. GZC20233247; and National Key Clinical Discipline; and the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases, No. 2020B1111170004.
Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki. All patients sampling and experimental procedures were approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (License No. 2024ZSLYEC-100).
Institutional animal care and use committee statement: Animal experiment was approved by the Guangzhou Forevergen Medical Laboratory Animal Center Animal Ethics Committee (License No. IACUC-AEWC-F2311019).
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: The data that support the findings of this study are available from the corresponding author on reasonable request.
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: Hong-Cheng Lin, Department of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuancun Erheng Road, Guangzhou 510655, Guangdong Province, China. lhcheng@mail.sysu.edu.cn
Received: February 13, 2025
Revised: March 19, 2025
Accepted: March 20, 2025
Published online: May 27, 2025
Processing time: 99 Days and 17 Hours
Abstract
BACKGROUND

The development of slow transit constipation (STC) is associated with intestinal barrier damage. Huangqi decoction (HQD) is effective in treating STC, but mechanisms are unclear.

AIM

To investigate whether HQD alleviates STC by downregulating the nuclear factor κB (NF-κB) signaling pathway and restoring intestinal barrier function.

METHODS

KM mice were divided into control, model, and HQD treatment groups. Fresh colonic tissues were collected for single-cell RNA sequencing and spatial transcriptome sequencing. The expressions of claudin-1, mucin 2, and NF-κB P65 proteins were detected by immunohistochemistry. In vitro experiments evaluated the effects of HQD on the LS174T cell line.

RESULTS

HQD improved intestinal motility, restored mucosal epithelium function and morphology. Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells, decreased mucin 2 secretion, and activated apoptotic pathways in STC mice. The population of intestinal stem cells was reduced, and proliferation along with Wnt/β-catenin pathways were inhibited. STC also altered the distribution of intestinal cell states, increasing immune-associated Enterocyte_C3. Aberrant NF-κB pathway activation was noted across various cell types. After HQD treatment, NF-κB pathway activity was down-regulated, while cell proliferation pathways were up-regulated, alongside an increase in Enterocyte_C1 related to material transport. Immunocytochemical, Western blot, and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice, with HQD inhibiting this aberrant activation.

CONCLUSION

STC involves intestinal mucosal barrier damage. HQD may treat STC by suppressing NF-κB signaling in epithelial cells, restoring intestinal epithelial cell function, and promoting mucosal barrier repair.

Keywords: Slow transit constipation; Huangqi decoction; Multi-omics; Intestinal barrier dysfunction; Protective effects

Core Tip: Huangqi decoction (HQD) alleviates slow transit constipation (STC) by suppressing the nuclear factor κB pathway and restoring intestinal barrier integrity. Employing single-cell RNA sequencing and spatial transcriptomics sequencing, we demonstrated HQD reverses STC-induced goblet cell depletion, enhances mucin 2 secretion, and reactivates Wnt/β-catenin-mediated intestinal stem cell proliferation. HQD downregulated nuclear factor κB signaling across cell types, notably inhibiting hyperactivation in goblet cells while promoting Enterocyte_C1 differentiation. These findings reveal HQD’s dual mechanism: Repairing mucosal barrier dysfunction via epithelial regulation and modulating enterocyte states, positioning it as a therapeutic strategy targeting mucosal repair in STC.