A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome

A herbal prescription in traditional Chinese medicine (TCM) has great complexity, with multiple components and multiple targets, making it extremely challenging to determine its bioactive compounds. Yinchenhao Tang (YCHT) has been extensively used for the treatment of jaundice disease. Although many...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hui Xiong, Ai-Hua Zhang, Ya-Jing Guo, Xiao-Hang Zhou, Hui Sun, Le Yang, Heng Fang, Guang-Li Yan, Xi-Jun Wang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Efficacy Bioactive compound Small molecule Targets Herbal medicine Metabolomics Engineering (General). Civil engineering (General) TA1-2040
Acceso en línea:	https://doaj.org/article/38538fe076fe48908e9167586e4c8ed5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:38538fe076fe48908e9167586e4c8ed5
record_format	dspace
spelling	oai:doaj.org-article:38538fe076fe48908e9167586e4c8ed52021-11-14T04:32:12ZA Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome2095-809910.1016/j.eng.2020.12.016https://doaj.org/article/38538fe076fe48908e9167586e4c8ed52021-09-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2095809921000527https://doaj.org/toc/2095-8099A herbal prescription in traditional Chinese medicine (TCM) has great complexity, with multiple components and multiple targets, making it extremely challenging to determine its bioactive compounds. Yinchenhao Tang (YCHT) has been extensively used for the treatment of jaundice disease. Although many studies have examined the efficacy and active ingredients of YCHT, there is still a lack of an in-depth systematic analysis of its effective components, mechanisms, and potential targets—especially one based on clinical patients. This study established an innovative strategy for discovering the potential targets and active compounds of YCHT based on an integrated clinical and animal experiment platform. The serum metabolic profiles and constituents of YCHT in vivo were determined by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-ToF-MS)-based metabolomics combined with a serum pharmacochemistry method. Moreover, a compound–target–pathway network was constructed and analyzed by network pharmacology and ingenuity pathway analysis (IPA). We found that eight active components could modulate five key targets. These key targets were further verified by enzyme-linked immunosorbent assay (ELISA), which indicated that YCHT exerts therapeutic effects by targeting cholesterol 7α-hydroxylase (CYP7A1), multidrug-resistance-associated protein 2 (ABCC2), multidrug-resistance-associated protein 3 (ABCC3), uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1), and farnesoid X receptor (FXR), and by regulating metabolic pathways including primary bile acid biosynthesis, porphyrin and chlorophyll metabolism, and biliary secretion. Eight main effective compounds were discovered and correlated with the key targets and pathways. In this way, we demonstrate that this integrated strategy can be successfully applied for the effective discovery of the active compounds and therapeutic targets of an herbal prescription.Hui XiongAi-Hua ZhangYa-Jing GuoXiao-Hang ZhouHui SunLe YangHeng FangGuang-Li YanXi-Jun WangElsevierarticleEfficacyBioactive compoundSmall moleculeTargetsHerbal medicineMetabolomicsEngineering (General). Civil engineering (General)TA1-2040ENEngineering, Vol 7, Iss 9, Pp 1293-1305 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Efficacy Bioactive compound Small molecule Targets Herbal medicine Metabolomics Engineering (General). Civil engineering (General) TA1-2040
spellingShingle	Efficacy Bioactive compound Small molecule Targets Herbal medicine Metabolomics Engineering (General). Civil engineering (General) TA1-2040 Hui Xiong Ai-Hua Zhang Ya-Jing Guo Xiao-Hang Zhou Hui Sun Le Yang Heng Fang Guang-Li Yan Xi-Jun Wang A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome
description	A herbal prescription in traditional Chinese medicine (TCM) has great complexity, with multiple components and multiple targets, making it extremely challenging to determine its bioactive compounds. Yinchenhao Tang (YCHT) has been extensively used for the treatment of jaundice disease. Although many studies have examined the efficacy and active ingredients of YCHT, there is still a lack of an in-depth systematic analysis of its effective components, mechanisms, and potential targets—especially one based on clinical patients. This study established an innovative strategy for discovering the potential targets and active compounds of YCHT based on an integrated clinical and animal experiment platform. The serum metabolic profiles and constituents of YCHT in vivo were determined by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-ToF-MS)-based metabolomics combined with a serum pharmacochemistry method. Moreover, a compound–target–pathway network was constructed and analyzed by network pharmacology and ingenuity pathway analysis (IPA). We found that eight active components could modulate five key targets. These key targets were further verified by enzyme-linked immunosorbent assay (ELISA), which indicated that YCHT exerts therapeutic effects by targeting cholesterol 7α-hydroxylase (CYP7A1), multidrug-resistance-associated protein 2 (ABCC2), multidrug-resistance-associated protein 3 (ABCC3), uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1), and farnesoid X receptor (FXR), and by regulating metabolic pathways including primary bile acid biosynthesis, porphyrin and chlorophyll metabolism, and biliary secretion. Eight main effective compounds were discovered and correlated with the key targets and pathways. In this way, we demonstrate that this integrated strategy can be successfully applied for the effective discovery of the active compounds and therapeutic targets of an herbal prescription.
format	article
author	Hui Xiong Ai-Hua Zhang Ya-Jing Guo Xiao-Hang Zhou Hui Sun Le Yang Heng Fang Guang-Li Yan Xi-Jun Wang
author_facet	Hui Xiong Ai-Hua Zhang Ya-Jing Guo Xiao-Hang Zhou Hui Sun Le Yang Heng Fang Guang-Li Yan Xi-Jun Wang
author_sort	Hui Xiong
title	A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome
title_short	A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome
title_full	A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome
title_fullStr	A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome
title_full_unstemmed	A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome
title_sort	clinical and animal experiment integrated platform for small-molecule screening reveals potential targets of bioactive compounds from a herbal prescription based on the therapeutic efficacy of yinchenhao tang for jaundice syndrome
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/38538fe076fe48908e9167586e4c8ed5
work_keys_str_mv	AT huixiong aclinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT aihuazhang aclinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT yajingguo aclinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT xiaohangzhou aclinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT huisun aclinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT leyang aclinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT hengfang aclinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT guangliyan aclinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT xijunwang aclinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT huixiong clinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT aihuazhang clinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT yajingguo clinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT xiaohangzhou clinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT huisun clinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT leyang clinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT hengfang clinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT guangliyan clinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome AT xijunwang clinicalandanimalexperimentintegratedplatformforsmallmoleculescreeningrevealspotentialtargetsofbioactivecompoundsfromaherbalprescriptionbasedonthetherapeuticefficacyofyinchenhaotangforjaundicesyndrome
_version_	1718429949934698496

A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome

Ejemplares similares