Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2025; 31(26): 105656
Published online Jul 14, 2025. doi: 10.3748/wjg.v31.i26.105656
Kushenol I combats ulcerative colitis via intestinal barrier preservation and gut microbiota optimization
Xu-Dong He, Min Li, Xiang-Duo Zuo, Hao-Yu Ni, Yu-Xin Han, Yun-Kai Hu, Jie Yu, Xing-Xin Yang
Xu-Dong He, Min Li, Xiang-Duo Zuo, Hao-Yu Ni, Yu-Xin Han, Yun-Kai Hu, Jie Yu, Xing-Xin Yang, College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming 650500, Yunnan Province, China
Xu-Dong He, Min Li, Xiang-Duo Zuo, Hao-Yu Ni, Yu-Xin Han, Yun-Kai Hu, Jie Yu, Xing-Xin Yang, Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Yunnan University of Chinese Medicine, Kunming 650500, Yunnan Province, China
Co-first authors: Xu-Dong He and Min Li.
Co-corresponding authors: Jie Yu and Xing-Xin Yang.
Author contributions: He XD, Li M, and Zuo XD wrote the manuscript; He XD, Li M, Zuo XD, Ni HY, Han YX, and Hu YK performed the experiments; He XD and Yu J performed the data analyses; He XD and Zuo XD provided technical support and helpful discussions; He XD, Li M, and Yang XX wrote and modified the manuscript; Yu J and Yang XX designed the study; All authors have read and agreed to the published version of the manuscript. He XD, Li M, and Zuo XD contributed equally to this work.
Supported by the National Natural Science Foundation of China, No. 82060707 and No. 82104381; Application and Basis Research Project of Yunnan China, No. 202201AW070016; Central Special Fund for Guiding Local Science and Technology Development, No. 202407AB110018; Engineering Research Center of Yunnan Education Department, No. 2022YGG03; and Open Research Fund Program of Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, No. 2019DG016.
Institutional review board statement: The study does not involve any human experiments.
Institutional animal care and use committee statement: According to the National Guidelines for Experimental Animal Welfare, all animal experiment protocols were approved by the Ethics Committee of the Experimental Animal Center at Yunnan University of Chinese Medicine (Approval No. R-062023111).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
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 upon reasonable request. Datasets are accessible directly via email communication with the corresponding author.
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: Xing-Xin Yang, MD, Professor, College of Pharmaceutical Science, Yunnan University of Chinese Medicine, No. 1076 Yuhua Road, Kunming 650500, Yunnan Province, China. yxx78945@163.com
Received: February 2, 2025
Revised: April 2, 2025
Accepted: May 26, 2025
Published online: July 14, 2025
Processing time: 159 Days and 19.8 Hours
Abstract
BACKGROUND

Kushenol I (KSCI) exhibits potential anti-inflammatory and antioxidant activities. However, its therapeutic effects and mechanisms in ulcerative colitis (UC) remain unclear.

AIM

To investigate the therapeutic effects and mechanisms of KSCI in alleviating UC.

METHODS

Therapeutic targets for KSCI in treating UC were identified using network pharmacology. Molecular docking and dynamics simulations confirmed the interactions between KSCI and these targets. In a murine UC model induced by dextran sodium sulfate (DSS), the anti-inflammatory and antioxidant effects of KSCI were evaluated following oral administration, as well as its impact on intestinal barrier function and immune response modulation. Finally, changes in gut microbiota composition were analyzed using 16S ribosomal RNA sequencing.

RESULTS

A total of 192 potential targets of KSCI in treating UC were identified using network pharmacology. KSCI bound stably to core targets including protein kinase B (AKT), p38 mitogen-activated protein kinase (p38 MAPK), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), phosphoinositide 3-kinase (PI3K), forkhead box O1 (FOXO1), and Toll-like receptor 4 (TLR4). The oral administration of KSCI improved colon length and body weight, and reduced disease activity in a mouse model of DSS-induced UC. KSCI suppressed pro-inflammatory cytokines (interleukin [IL-1β], IL-6, IL-17, and tumor necrosis factor alpha) and promoted the expression of the anti-inflammatory cytokine IL-10. It also inhibited key signaling molecules and modulated the expression of IL-1β, AKT, p38 MAPK, NLRP3, PI3K, AKT, FOXO1, and TLR4. KSCI exhibited potent antioxidant effects, ameliorating colonic inflammation and tissue damage. It improved intestinal barrier function, influenced gut microbiota composition, and increased splenic T-cell percentages.

CONCLUSION

KSCI alleviated DSS-induced UC by modulating gut microbiota, enhancing the intestinal barrier, reducing inflammation and oxidative stress, and regulating the immune response.

Keywords: Kushenol I; Ulcerative colitis; Gut microbiota; Sophora flavescens Aiton; Network pharmacology; Intestinal integrity

Core Tip: Kushenol I (KSCI) from Sophora flavescens shows promise for treating ulcerative colitis (UC). Network pharmacology reveals 192 potential targets, including protein kinase B, NOD-like receptor thermal protein domain associated protein 3, Toll-like receptor 4, phosphoinositide 3-kinase, and forkhead box O1. In UC mice, KSCI alleviates symptoms, reduces pro-inflammatory cytokines, enhances anti-inflammatory activity, and inhibits the activation of key signaling pathways. It also exerts antioxidant effects, repairs intestinal barrier damage, and modulates the gut microbiota. Additionally, KSCI regulates T-cell balance. These findings highlight KSCI’s multi-target mechanism offering potential as a therapeutic agent for UC.