Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2025; 31(9): 100271
Published online Mar 7, 2025. doi: 10.3748/wjg.v31.i9.100271
Network pharmacology and in vivo study: Unraveling the therapeutic mechanisms of Panax ginseng in potentially treating ulcerative colitis
Yan Qin, Rui-Ya Zhang, Yu Zhang, Yi-Qing Zhao, Hai-Feng Hao, Jun-Ping Wang
Yan Qin, Rui-Ya Zhang, Yu Zhang, Yi-Qing Zhao, Jun-Ping Wang, Department of Gastroenterology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
Hai-Feng Hao, Department of Urology, The First Hospital of Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
Author contributions: Wang JP and Qin Y conceived and designed the study; Qin Y and Zhang RY conducted network pharmacology analysis and analyzed the data; Qin Y, Zhang Y and Zhao YQ performed the animal experiments; Qin Y wrote the manuscript; Hao HF and Wang JP revised the manuscript; Wang JP obtained funding for the study; All authors have read and agreed to the final version of the manuscript published.
Supported by Provincial Key Cultivation Laboratory for Digestive Disease Research, Shanxi Province’s “Si Ge Yi Pi” Science and Technology Driven Medical Innovation Project, No. 2021SYS13, No. 2020SYS13 and No. 2021MX03.
Institutional animal care and use committee statement: This study was approved by the Ethics Committee of the Shanxi Provincial People’s Hospital [(2024) No. 506]. All animal experiments were conducted according to a protocol approved by the Institutional Animal Care Committee of Shanxi Provincial People’s Hospital, No. SYXK(Jin) 2024-0002.
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 datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request at wangjp8396@sxmu.edu.cn.
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: Jun-Ping Wang, MD, Professor, Department of Gastroenterology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical University, No. 29 Shuangtasi Street, Taiyuan 030012, Shanxi Province, China. wangjp8396@sxmu.edu.cn
Received: August 12, 2024
Revised: December 8, 2024
Accepted: January 13, 2025
Published online: March 7, 2025
Processing time: 190 Days and 6.2 Hours
Abstract
BACKGROUND

Ulcerative colitis (UC), a chronic and challenging condition, necessitates the development of more effective treatments owing to the unsatisfactory efficacy and side effects associated with current medications. Traditional Chinese medicine (TCM), known for its multi-stage and multi-targeted approach, has a long history in treating gastrointestinal diseases and offering a promising alternative UC treatment. Panax ginseng (P. ginseng), a commonly used remedy for UC in TCM, exemplifies this potential, although the specific components and mechanisms through which its therapeutic effects are exerted remain to be fully elucidated, highlighting the need for further research to unlock its full potential as a treatment option.

AIM

To investigate the key constituents and biological pathways through which P. ginseng exerts therapeutic effects on UC.

METHODS

Network pharmacology investigated the UC-alleviating mechanism of P. ginseng, including “active ingredient-target-disease” network analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Panaxadiol (PD; active ingredient of P. ginseng) was tested in a mouse model of 3% dextran sulfate sodium-induced UC, with assessments of body weight, Disease Activity Index scores, and colon length. Colitis and intestinal barrier integrity were analyzed via hematoxylin-eosin and Alcian blue and periodic acid-Schiff staining, immunohistochemistry, real time-quantitative PCR, and western blotting.

RESULTS

By integrating and analyzing the targets of P. ginseng and UC, 15 critical hub genes were discovered. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the mechanisms involved to be linked to MAPK and PI3K-Akt signaling. Among the 10 main active ingredients identified as potentially effective, PD was most abundant and was validated in vivo to mitigate weight loss, reduce Disease Activity Index scores, and prevent colon shortening. PD also reduced inflammation and suppressed expression of pro-inflammatory cytokines and mediators. In addition, PD increased expression of mucin and tight junction proteins. Ultimately, PD counteracted effects of dextran sulfate sodium by inhibiting phosphorylation of NF-кB and MAPK, while increasing phosphorylation of AMPK and expression of NRF2 and NQO1.

CONCLUSION

PD alleviates colitis and aids intestinal barrier repair, partly via modulation of the MAPK/NF-кB and AMPK/NRF2/NQO1 pathways. These findings also suggest new research methods for treatment of UC with TCM.

Keywords: Ulcerative colitis; Panax ginseng; Network pharmacology; Panaxadiol; MAPK; NF-κB; AMPK; NRF2

Core Tip: Panax ginseng (P. ginseng) is widely used to treat ulcerative colitis (UC) and known for its therapeutic efficacy. However, the specific components and mechanisms underlying its action require further clarification. Using network pharmacology analysis, we identified the main components of P. ginseng in treating UC, with panaxadiol (PD) emerging as the most abundant and potentially critical component. Next, we validated the role of PD in a mouse model of dextran sulfate sodium-induced colitis. The results demonstrated that PD effectively alleviates colitis and helps repair the intestinal barrier, partly via modulation of the MAPK/NF-кB and AMPK/NRF2/NQO1 signaling pathways.