Mechanism of interventional effect and targets of Zhuyu pill in regulating and suppressing colitis and cholestasis

Zhuyu pill (ZYP) is a traditional Chinese medicine prescription composed of two drugs, Coptis chinensis Franch. and Tetradium ruticarpum (A. Jussieu) T. G. Hartley, and is commonly used in the clinical treatment of diseases of the digestive system. However, the mechanism underlying the effect of ZYP...

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Main Authors: Han Yu, Fenghua Zhang, Yueqiang Wen, Zhili Zheng, Gaoyang Chen, Yingying Pan, Peijie Wu, Qiaobo Ye, Jun Han, Xiaofeng Chen, Chao Liu, Tao Shen
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.1038188/full
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author Han Yu
Fenghua Zhang
Yueqiang Wen
Yueqiang Wen
Zhili Zheng
Gaoyang Chen
Yingying Pan
Peijie Wu
Qiaobo Ye
Jun Han
Xiaofeng Chen
Chao Liu
Tao Shen
author_facet Han Yu
Fenghua Zhang
Yueqiang Wen
Yueqiang Wen
Zhili Zheng
Gaoyang Chen
Yingying Pan
Peijie Wu
Qiaobo Ye
Jun Han
Xiaofeng Chen
Chao Liu
Tao Shen
author_sort Han Yu
collection DOAJ
description Zhuyu pill (ZYP) is a traditional Chinese medicine prescription composed of two drugs, Coptis chinensis Franch. and Tetradium ruticarpum (A. Jussieu) T. G. Hartley, and is commonly used in the clinical treatment of diseases of the digestive system. However, the mechanism underlying the effect of ZYP on colitis remains unclear. In this study, a colitis rat model was induced with 2,4,6-trinitro-benzenesulfonic acid (TNBS, 100 mg/kg) and treated with ZYP (low dose: 0.6 g/kg, high dose: 1.2 g/kg). Disease activity index, colonic weight index, and weight change ratio were used to evaluate the model and efficacy. LC-MS and 16S rRNA gene sequencing were used to measure differences in fecal metabolism and microorganism population among the control, model, low-dose ZYP, and high-dose ZYP groups. To elucidate the mechanism of interventional effect of ZYP, Spearman correlation analysis was used to analyze the correlation between fecal metabolism and fecal microbial number. High-dose and low-dose ZYP both exhibited significant interventional effects on colitis rat models, and high-dose ZYP produced a better interventional effect compared with low-dose ZYP. Based on a metabolomics test of fecal samples, significantly altered metabolites in the model and high-dose ZYP treatment groups were identified. In total, 492 metabolites were differentially expressed. Additionally, sequencing of the 16S rRNA gene in fecal samples revealed that the high-dose ZYP could improve TNBS-induced fecal microbiota dysbiosis. Ultimately, changes in tryptophan metabolism and Firmicutes and Gammaproteobacteria populations were detected after ZYP treatment in both colitis and cholestasis. Therefore, we conclude that tryptophan metabolism and Firmicutes and Gammaproteobacteria populations are the core targets of the anti-inflammatory effect of ZYP. These findings provide a scientific basis for further investigation of the anti-inflammatory mechanism of ZYP in the future.
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spelling doaj.art-049086b0ea854e75b7104fbbcb135a252022-12-22T03:56:58ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-11-011310.3389/fphar.2022.10381881038188Mechanism of interventional effect and targets of Zhuyu pill in regulating and suppressing colitis and cholestasisHan Yu0Fenghua Zhang1Yueqiang Wen2Yueqiang Wen3Zhili Zheng4Gaoyang Chen5Yingying Pan6Peijie Wu7Qiaobo Ye8Jun Han9Xiaofeng Chen10Chao Liu11Tao Shen12School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Pediatrics, Guang’an Hospital of Traditional Chinese Medicine, Guang’an, ChinaDepartment of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaZhuyu pill (ZYP) is a traditional Chinese medicine prescription composed of two drugs, Coptis chinensis Franch. and Tetradium ruticarpum (A. Jussieu) T. G. Hartley, and is commonly used in the clinical treatment of diseases of the digestive system. However, the mechanism underlying the effect of ZYP on colitis remains unclear. In this study, a colitis rat model was induced with 2,4,6-trinitro-benzenesulfonic acid (TNBS, 100 mg/kg) and treated with ZYP (low dose: 0.6 g/kg, high dose: 1.2 g/kg). Disease activity index, colonic weight index, and weight change ratio were used to evaluate the model and efficacy. LC-MS and 16S rRNA gene sequencing were used to measure differences in fecal metabolism and microorganism population among the control, model, low-dose ZYP, and high-dose ZYP groups. To elucidate the mechanism of interventional effect of ZYP, Spearman correlation analysis was used to analyze the correlation between fecal metabolism and fecal microbial number. High-dose and low-dose ZYP both exhibited significant interventional effects on colitis rat models, and high-dose ZYP produced a better interventional effect compared with low-dose ZYP. Based on a metabolomics test of fecal samples, significantly altered metabolites in the model and high-dose ZYP treatment groups were identified. In total, 492 metabolites were differentially expressed. Additionally, sequencing of the 16S rRNA gene in fecal samples revealed that the high-dose ZYP could improve TNBS-induced fecal microbiota dysbiosis. Ultimately, changes in tryptophan metabolism and Firmicutes and Gammaproteobacteria populations were detected after ZYP treatment in both colitis and cholestasis. Therefore, we conclude that tryptophan metabolism and Firmicutes and Gammaproteobacteria populations are the core targets of the anti-inflammatory effect of ZYP. These findings provide a scientific basis for further investigation of the anti-inflammatory mechanism of ZYP in the future.https://www.frontiersin.org/articles/10.3389/fphar.2022.1038188/fullcholestasiscolitiscommon interventional mechanismfecal microbial diversityfecal metabolismZhuyu pill
spellingShingle Han Yu
Fenghua Zhang
Yueqiang Wen
Yueqiang Wen
Zhili Zheng
Gaoyang Chen
Yingying Pan
Peijie Wu
Qiaobo Ye
Jun Han
Xiaofeng Chen
Chao Liu
Tao Shen
Mechanism of interventional effect and targets of Zhuyu pill in regulating and suppressing colitis and cholestasis
Frontiers in Pharmacology
cholestasis
colitis
common interventional mechanism
fecal microbial diversity
fecal metabolism
Zhuyu pill
title Mechanism of interventional effect and targets of Zhuyu pill in regulating and suppressing colitis and cholestasis
title_full Mechanism of interventional effect and targets of Zhuyu pill in regulating and suppressing colitis and cholestasis
title_fullStr Mechanism of interventional effect and targets of Zhuyu pill in regulating and suppressing colitis and cholestasis
title_full_unstemmed Mechanism of interventional effect and targets of Zhuyu pill in regulating and suppressing colitis and cholestasis
title_short Mechanism of interventional effect and targets of Zhuyu pill in regulating and suppressing colitis and cholestasis
title_sort mechanism of interventional effect and targets of zhuyu pill in regulating and suppressing colitis and cholestasis
topic cholestasis
colitis
common interventional mechanism
fecal microbial diversity
fecal metabolism
Zhuyu pill
url https://www.frontiersin.org/articles/10.3389/fphar.2022.1038188/full
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