Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2019; 25(21): 2603-2622
Published online Jun 7, 2019. doi: 10.3748/wjg.v25.i21.2603
Systems pharmacology approach reveals protective mechanisms of Jian-Pi Qing-Chang decoction on ulcerative colitis
You-Lan Chen, Yi-Yuan Zheng, Yan-Cheng Dai, Ya-Li Zhang, Zhi-Peng Tang
You-Lan Chen, Yi-Yuan Zheng, Yan-Cheng Dai, Ya-Li Zhang, Zhi-Peng Tang, Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Yan-Cheng Dai, Department of Gastroenterology, Shanghai Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200082, China
Author contributions: Chen YL and Zheng YY contributed equally as co-first authors and finished the major experiments; Dai YC and Zhang YL performed the experiments and analyzed the data; Tang ZP provided the funding and designed the research; all authors read and approved the final manuscript.
Supported by the National Natural Science Funds of China, No. 81573892, No. 81873253, and No. 81704009.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Shanghai University of Traditional Chinese Medicine (IACUC protocol number Approval number: SZY201707005).
Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study.
Data sharing statement: Supplementary information accompanying this paper is included in its Supplementary information file.
ARRIVE guidelines statement: The ARRIVE Guidelines have been adopted.
Open-Access: 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/
Corresponding author: Zhi-Peng Tang, MD, PhD, Director, Doctor, Professor, Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, No. 725, South Wanping Road, Shanghai 200032, China. zhipengtang@sohu.com
Telephone: +86-21-64385700 Fax: +86-21-64385700
Received: March 2, 2019
Peer-review started: March 3, 2019
First decision: March 20, 2019
Revised: March 27, 2019
Accepted: April 19, 2019
Article in press: April 20, 2019
Published online: June 7, 2019
Processing time: 96 Days and 19.8 Hours
Abstract
BACKGROUND

Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese medicine (TCM) provides new options for the standard therapy. Nevertheless, there are still numerous problems with the promotion of TCM attributed to its complexity, and consequently, new research approaches are urgently needed. Thus, we explored the protective effects of Jian-Pi Qing-Chang (JPQC) decoction on UC based on systems pharmacology approach, which might fill the current innovation gap in drug discovery and clinical practice pertaining to TCM.

AIM

To investigate the protective mechanisms of JPQC decoction on UC based on systems pharmacology approach.

METHODS

We performed systems pharmacology to predict the active ingredients, the matched targets, and the potential pharmacological mechanism of JPQC on UC. In vivo, we explored the effects of JPQC in a colitis model induced by dextran sulfate sodium. In vitro, we adopted the bone marrow-derived macrophages (BMDMs) as well as BMDMs co-cultured with Caco2 cells to verify the underlying mechanisms and effects of JPQC on UC under TNF-α stimulation.

RESULTS

Systems pharmacology revealed 170 targets for the 107 active ingredients of JPQC and 112 candidate targets of UC. Protein-protein interaction networks were established to identify the underlying therapeutic targets of JPQC on UC. Based on enrichment analyses, we proposed our hypothesis that JPQC might have a protective effect on UC via the NF-κB/HIF-1α signalling pathway. Subsequent experimental validation revealed that treatment with TNFα activated the NF-κB/HIF-1α signalling pathway in BMDMs, thereby damaging the epithelial barrier permeability in co-cultured Caco2 cells, while JPQC rescued this situation. The findings were also confirmed in a dextran sulfate sodium-induced colitis model.

CONCLUSION

JPQC could improve the mucosal inflammatory response and intestinal epithelial barrier function via the NF-κB/HIF-1α signalling pathway, which provides new perspectives on the pharmaceutical development and clinical practice of TCM.

Keywords: Systems pharmacology; Ulcerative colitis; Jian-Pi Qing-Chang decoction; Inflammation; Intestinal epithelial barrier function

Core tip: Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese medicine (TCM) provides new options for the standard therapy. Nevertheless, there are still numerous problems with the promotion of TCM attributed to its complexity, and consequently, new research approaches are urgently needed. Thus, we explored the protective effects of Jian-Pi Qing-Chang decoction on UC based on systems pharmacology approach, which might fill the current innovation gap in drug discovery and clinical practice pertaining to TCM.