Mechanism of Paeoniflorin in the Treatment of Bile Duct Ligation-Induced Cholestatic Liver Injury Using Integrated Metabolomics and Network Pharmacology

Frontiers in Pharmacology
Shizhang WeiYanling Zhao

Abstract

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, ILB...Continue Reading

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Methods Mentioned

BETA
light microscopy
PCA

Software Mentioned

MassHunter Profinder
Cytoscape
Pro Plus
MetaboAnalyst
MBROLE
OPLS
SIMCA
SPSS
DA
PharmMapper Server

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