Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2022; 28(34): 5007-5022
Published online Sep 14, 2022. doi: 10.3748/wjg.v28.i34.5007
Ji-Chuan decoction ameliorates slow transit constipation via regulation of intestinal glial cell apoptosis
Xiu-Min Wang, Li-Xia Lv, Yue-Si Qin, Yu-Zhu Zhang, Ni Yang, Shu Wu, Xiu-Wen Xia, Hong Yang, Hong Xu, Ying Liu, Wei-Jun Ding
Xiu-Min Wang, Yu-Zhu Zhang, Ni Yang, Shu Wu, Xiu-Wen Xia, Hong Yang, Wei-Jun Ding, Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
Xiu-Min Wang, Hong Xu, Department of Proctology, Chengdu First People’s Hospital, Chengdu 610041, Sichuan Province, China
Li-Xia Lv, Department of Endocrinology and Metabolism, Chengdu First People’s Hospital, Chengdu 610041, Sichuan Province, China
Yue-Si Qin, Department of Dermatology, Chengdu First People’s Hospital, Chengdu 610041, Sichuan Province, China
Ying Liu, Department of Preventive Medicine, Shantou University Medical College, Shantou 515063, Guangdong Province, China
Author contributions: Wang XM, Xu H, and Ding WJ designed and coordinated the study; Wang XM, Lv LX, Qin YS, Zhang YZ, Yang N, Wu S, Xia XW, and Yang H performed the experiments and acquired and analyzed the data; Liu Y interpreted the data; Ding WJ contributed to critical revision of the manuscript; and all authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82074151; and the Experimental Formulary Sichuan Youth Science and Technology Innovation Research Team, No. 2020JDTD0022.
Institutional animal care and use committee statement: This experiment was approved by the Animal Ethics Committee, Chengdu University of TCM (license 2016-16).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
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: Wei-Jun Ding, PhD, Full Professor, Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine, No. 1166 Liutai Avenue, Wenjiang District, Chengdu 610072, Sichuan Province, China. dingweijun@cdutcm.edu.cn
Received: May 20, 2022
Peer-review started: May 20, 2022
First decision: July 13, 2022
Revised: July 19, 2022
Accepted: August 21, 2022
Article in press: August 21, 2022
Published online: September 14, 2022
Processing time: 110 Days and 4.9 Hours
Abstract
BACKGROUND

Slow transit constipation (STC) is a common intestinal disease with increasing incidence. STC results from various factors, such as the enteric nervous system and metabolic changes. As a classical formula of traditional Chinese medicine, Ji-Chuan decoction (JCD) has been extensively and effectively used in STC treatment, yet its pharmacological mechanism remains unclear.

AIM

To explore the integrated regulatory pattern of JCD against STC through hyphenated techniques from metabolism, network pharmacology and molecular methods.

METHODS

STC model mice were generated by intragastric administration of compound diphenoxylate (10 mg/kg/d) for 14 d. The STC mice in the low dose of JCD (3.04 g/kg), middle dose of JCD (6.08 g/kg) and high dose of JCD (12.16 g/kg) groups were orally administered JCD solution once a day for 2 wk. The acetylcholine (ACH) level was examined by enzyme-linked immunosorbent assay. The pathological features of colon tissue were observed by hematoxylin and eosin staining. The differentially expressed metabolites and metabolic pathways were tested by nontargeted metabolomics. The main targets and core ingredients of JCD were identified by network pharmacology, and the expression of AKT was confirmed by immunohistochemistry. Finally, the pathways involved in JCD treatment were predicted using a combination of differentially expressed metabolites and targets, and intestinal glial cell apoptosis was demonstrated by immunofluorescence.

RESULTS

JCD significantly promoted intestinal motility, increased the levels of the excitatory neurotransmitter ACH and reduced intestinal inflammation in STC mice. Untargeted metabolomics results showed that JCD significantly restored metabolic dysfunction and significantly affected taurine and hypotaurine metabolism. Network pharmacology and molecular experiments showed that JCD regulates AKT protein expression, and the core component is quercetin. Combined analysis demonstrated that apoptosis may be an important mechanism by which JCD relieves constipation. Further experiments showed that JCD reduced enteric glial cell (EGC) apoptosis.

CONCLUSION

This work demonstrated that reducing EGC apoptosis may be the critical mechanism by which JCD treats STC. These findings call for further molecular research to facilitate the clinical application of JCD.

Keywords: Slow-transit constipation; Ji-Chuan decoction; Taurine and hypotaurine metabolism; AKT; Enteric glial cell; Apoptosis

Core Tip: Slow transit constipation (STC) model mice, which were established with compound diphenoxylate, were effectively treated with Ji-Chuan decoction (JCD). The results show that JCD can promote intestinal motility, increase acetylcholine content, reduce enteric inflammation, improve metabolic dysfunction, and reduce enteric glial cell apoptosis. This work demonstrated that reducing enteric glial cell apoptosis may be the critical mechanism by which JCD treats STC. These findings call for further molecular research to facilitate the clinical application of JCD.