Mechanism of Paeoniflorin in the Treatment of Bile Duct Ligation-Induced Cholestatic Liver Injury Using Integrated Metabolomics and Network Pharmacology
Paeoniflorin (PF) is the main active component of Paeonia lactiflora Pall., which is used in the treatment of severe cholestatic hepatitis. However, its biological mechanism in regulating bile acid metabolism and cholestatic liver injury has not been fully revealed. Our study aimed to reveal the mec...
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doaj-44b85245ee054e998f39befd8d4732fa2020-11-25T03:42:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-10-011110.3389/fphar.2020.586806586806Mechanism of Paeoniflorin in the Treatment of Bile Duct Ligation-Induced Cholestatic Liver Injury Using Integrated Metabolomics and Network PharmacologyShizhang Wei0Shizhang Wei1Xiao Ma2Ming Niu3Ruilin Wang4Tao Yang5Tao Yang6Dan Wang7Dan Wang8Jianxia Wen9Jianxia Wen10Haotian Li11Yanling Zhao12College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Pharmacy, PLA General Hospital, Beijing, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaChina Military Institute of Chinese Medicine, The Fifth Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Integrative Medical Center, The Fifth Medical Center of PLA General Hospital, Beijing, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Pharmacy, PLA General Hospital, Beijing, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Pharmacy, PLA General Hospital, Beijing, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Pharmacy, PLA General Hospital, Beijing, ChinaDepartment of Pharmacy, PLA General Hospital, Beijing, ChinaDepartment of Pharmacy, PLA General Hospital, Beijing, ChinaPaeoniflorin (PF) is the main active component of Paeonia lactiflora Pall., which is used in the treatment of severe cholestatic hepatitis. However, its biological mechanism in regulating bile acid metabolism and cholestatic liver injury has not been fully revealed. Our study aimed to reveal the mechanism of PF in the treatment of cholestatic liver injury in an in vivo metabolic environment using bioinformatics analysis. The serum of rats with bile duct ligation (BDL)-induced cholestatic liver injury treated with PF was analyzed by UHPLC-Q-TOF, and specific metabolites were screened using a metabolomics method. These specific metabolites were further analyzed by network pharmacology to identify the upstream signaling pathways and key protein targets. Finally, the key target proteins were verified by immunohistochemistry using cholestatic rat liver tissue. The serum ALT, AST, TBA, and TBIL levels, as well as the pathological state of the liver tissues, were significantly improved by PF. Twenty-five specific metabolites and 157 corresponding target proteins were screened for the treatment of cholestatic liver injury by PF. The “PF-target-metabolite” interaction network was constructed, and five protein targets (MAP2K1, MAPK1, ILBP, ABCB1, and LTA4H) that may regulate specific metabolites were obtained. The results of immunohistochemistry showed that PF improved the expression of these proteins. The integrated application of multiple bioinformatics methods revealed that PF plays a key role in the treatment of cholestatic liver injury by intervening in important targets related to bile acid metabolism and inflammation.https://www.frontiersin.org/articles/10.3389/fphar.2020.586806/fullpaeoniflorincholestasisbile duct ligationmetabolomicsnetwork pharmacology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shizhang Wei Shizhang Wei Xiao Ma Ming Niu Ruilin Wang Tao Yang Tao Yang Dan Wang Dan Wang Jianxia Wen Jianxia Wen Haotian Li Yanling Zhao |
spellingShingle |
Shizhang Wei Shizhang Wei Xiao Ma Ming Niu Ruilin Wang Tao Yang Tao Yang Dan Wang Dan Wang Jianxia Wen Jianxia Wen Haotian Li Yanling Zhao Mechanism of Paeoniflorin in the Treatment of Bile Duct Ligation-Induced Cholestatic Liver Injury Using Integrated Metabolomics and Network Pharmacology Frontiers in Pharmacology paeoniflorin cholestasis bile duct ligation metabolomics network pharmacology |
author_facet |
Shizhang Wei Shizhang Wei Xiao Ma Ming Niu Ruilin Wang Tao Yang Tao Yang Dan Wang Dan Wang Jianxia Wen Jianxia Wen Haotian Li Yanling Zhao |
author_sort |
Shizhang Wei |
title |
Mechanism of Paeoniflorin in the Treatment of Bile Duct Ligation-Induced Cholestatic Liver Injury Using Integrated Metabolomics and Network Pharmacology |
title_short |
Mechanism of Paeoniflorin in the Treatment of Bile Duct Ligation-Induced Cholestatic Liver Injury Using Integrated Metabolomics and Network Pharmacology |
title_full |
Mechanism of Paeoniflorin in the Treatment of Bile Duct Ligation-Induced Cholestatic Liver Injury Using Integrated Metabolomics and Network Pharmacology |
title_fullStr |
Mechanism of Paeoniflorin in the Treatment of Bile Duct Ligation-Induced Cholestatic Liver Injury Using Integrated Metabolomics and Network Pharmacology |
title_full_unstemmed |
Mechanism of Paeoniflorin in the Treatment of Bile Duct Ligation-Induced Cholestatic Liver Injury Using Integrated Metabolomics and Network Pharmacology |
title_sort |
mechanism of paeoniflorin in the treatment of bile duct ligation-induced cholestatic liver injury using integrated metabolomics and network pharmacology |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2020-10-01 |
description |
Paeoniflorin (PF) is the main active component of Paeonia lactiflora Pall., which is used in the treatment of severe cholestatic hepatitis. However, its biological mechanism in regulating bile acid metabolism and cholestatic liver injury has not been fully revealed. Our study aimed to reveal the mechanism of PF in the treatment of cholestatic liver injury in an in vivo metabolic environment using bioinformatics analysis. The serum of rats with bile duct ligation (BDL)-induced cholestatic liver injury treated with PF was analyzed by UHPLC-Q-TOF, and specific metabolites were screened using a metabolomics method. These specific metabolites were further analyzed by network pharmacology to identify the upstream signaling pathways and key protein targets. Finally, the key target proteins were verified by immunohistochemistry using cholestatic rat liver tissue. The serum ALT, AST, TBA, and TBIL levels, as well as the pathological state of the liver tissues, were significantly improved by PF. Twenty-five specific metabolites and 157 corresponding target proteins were screened for the treatment of cholestatic liver injury by PF. The “PF-target-metabolite” interaction network was constructed, and five protein targets (MAP2K1, MAPK1, ILBP, ABCB1, and LTA4H) that may regulate specific metabolites were obtained. The results of immunohistochemistry showed that PF improved the expression of these proteins. The integrated application of multiple bioinformatics methods revealed that PF plays a key role in the treatment of cholestatic liver injury by intervening in important targets related to bile acid metabolism and inflammation. |
topic |
paeoniflorin cholestasis bile duct ligation metabolomics network pharmacology |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2020.586806/full |
work_keys_str_mv |
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