Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2019; 25(34): 5134-5151
Published online Sep 14, 2019. doi: 10.3748/wjg.v25.i34.5134
Effect of Tong Xie Yao Fang on endogenous metabolites in urine of irritable bowel syndrome model rats
Xue-Ying Zhao, Jian-Wei Wang, Yue Yin, Kai Li, Miao Zhang, Fu-Ping Yan
Xue-Ying Zhao, Jian-Wei Wang, Yue Yin, Kai Li, Miao Zhang, Fu-Ping Yan, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
Author contributions: Zhao XY and Wang JW performed most of the experiments, analyzed the experimental results, interpreted them and wrote the manuscript; Yin Y, Li K, Zhang M and Yan FP performed some experiments and interpretation of the results; Wang JW participated in the testing factor design and revised the manuscript. She is also the corresponding author; All co-authors participated in writing and checking the manuscript and approved the submitted manuscript.
Supported by the National Natural Science Foundation of China, No. 81573870; the Eighth Special Subsidy Project of China Post-Doctoral Science Foundation, No. 2015T80376; Postdoctoral Science-Research Developmental Foundation of China, No. 2013M531079; National Science Foundation of Heilongjiang Province, No. H2015020; Heilongjiang University of Traditional Chinese Medicine Outstanding Innovative Talents Support Project (Outstanding Young Academic Leaders), Postdoctoral Science-Research Developmental Foundation of Heilongjiang Province, No. LBH-Q12009; Youth Academic Backbone Fund of Heilongjiang Province Education Department, No. 1253G053; Youth Science and Technology Project of Traditional Chinese Medicine Department of Heilongjiang Province, No. ZQG-034.
Institutional review board statement: This study was approved by the Ethics Committee of the Heilongjiang University of Chinese Medicine.
Institutional animal care and use committee statement: This study was approved by the animal care and use committee of the Heilongjiang University of Chinese Medicine.
Conflict-of-interest statement: Authors declare no conflicts of interest.
Data sharing statement: The detailed experimental methods are available from the corresponding author at xueyingzhao2010@126.com and wangjianwei140918@126.com.
ARRIVE guidelines statement: The ARRIVE Guidelines have been adopted.
Open-Access: This 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 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: Jian-Wei Wang, PhD, Professor, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, Heilongjiang Province, China. wangjianwei140918@126.com
Telephone: +86-451-82193640
Received: April 18, 2019
Peer-review started: April 18, 2019
First decision: July 22, 2019
Revised: July 30, 2019
Accepted: August 19, 2019
Article in press: August 19, 2019
Published online: September 14, 2019
Processing time: 147 Days and 7.8 Hours
Abstract
BACKGROUND

Tong Xie Yao Fang is a representative traditional Chinese prescription for the treatment of liver and spleen deficiency, abdominal pain and diarrhea. It has a unique function in the treatment of gastrointestinal dysfunction including irritable bowel syndrome (IBS), is a common functional bowel disease. Its main symptoms are recurrent abdominal pain, diarrhea, constipation or alternations between diarrhea and constipation.

There are obvious differences in metabolites between TCM syndromes. By comparing the body fluid metabolism maps of model animals, metabolomics can discover disease biomarkers, analyze the differences in metabolic pathways and understand the pathological process and the metabolic pathways of substances in the body. Thus, the evaluation of animal models tends to be comprehensive and objective. This may provide further understanding between the interaction between Tong Xie Yao Fang and the IBS model.

AIM

To evaluate the effect of Tong Xie Yao Fang on IBS rats by using metabolomics method.

METHODS

Wistar rats were used to establish IBS models, and then randomly divided into four groups: A model control group and three Tong Xie Yao Fang treatment groups (high, medium and low doses). A normal, non-IBS group was established. The rats were treated for 2 wk. On days 0 and 14 of the experimental model, urine was collected for 12 h and was analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Nine potential biomarkers were identified, and six major metabolic pathways were found to be related to IBS.

RESULTS

In the study of metabonomics, nine potential biomarkers including L-serine, 4-methylgallic acid, L-threonine, succinylacetone, prolyl-hydroxyproline, valyl-serine, acetyl citrate, marmesin rutinoside and 5-hydroxy-L-tryptophan were identified in urine, which were assigned to amino acids, organic acids, succinyl and glycosides. Furthermore, the metabolic pathway of L-serine, L-threonine and 5-hydroxy-L-tryptophan was found in the Kyoto Encyclopedia of Genes and Genomes, which mainly involved the metabolism of cysteine and methionine, vitamin B6 metabolism, serotonin synapse, tryptophan metabolism, sphingolipid metabolism, digestion, absorption of protein and amino acid metabolism. These pathways are related to intestinal dysfunction, inflammatory syndrome, nervous system dysfunction and other diseases.

CONCLUSION

Tong Xie Yao Fang has pharmacological effects on IBS, and its mechanism may be related to the metabolism of the nine potential biomarkers identified above in urine.

Keywords: Tong Xie Yao Fang; Irritable bowel syndrome; Liver-spleen disharmony; Endogenous metabolites; Metabolomics

Core tip: Effects of Tong Xie Yao Fang on endogenous metabolites in urine of irritable bowel syndrome model rats were investigated through ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Tong Xie Yao Fang has the function of callback endogenous metabolite. Nine potential biomarkers were identified, and six main metabolic pathways were analyzed. They were related to neurotransmitter metabolism, inflammatory immunity, emotional changes and energy metabolism in irritable bowel syndrome disease, which may be the biological basis of irritable bowel syndrome spleen deficiency and liver hyperactivity syndrome.