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A Network Pharmacology Study of the Molecular Mechanisms of Hypericum japonicum in the Treatment of Cholestatic Hepatitis with Validation in an Alpha-Naphthylisothiocyanate (ANIT) Hepatotoxicity Rat Model

Authors
  • Feng, Sen Ling1
  • Zhang, Jing2
  • Jin, Hongliu1
  • Zhu, Wen Ting1
  • Yuan, Zhongwen1
  • 1 Department of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China
  • 2 Department of Pharmacy, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, P.R. China
Type
Published Article
Journal
Medical Science Monitor
Publisher
"International Scientific Information, Inc."
Publication Date
Mar 03, 2021
Volume
27
Identifiers
DOI: 10.12659/MSM.928402
PMID: 33657087
PMCID: PMC7938440
Source
PubMed Central
Keywords
License
Green

Abstract

Background This network pharmacology study aimed to identify the active compounds and molecular mechanisms involved in the effects of Hypericum japonicum on cholestatic hepatitis. We validated the findings in an alpha-naphthylisothiocyanate (ANIT) rat model of hepatotoxicity. Material/Methods The chemical constituents and targets of H. japonicum and target genes previously associated with cholestatic hepatitis were retrieved from public databases. A network was constructed using Cytoscape 3.7.2 software and the STRING database and potential protein functions were analyzed based on the public platform of bioinformatics. ANIT was used to induce cholestatic hepatitis in a rat model using 36 Sprague-Dawley rats, and this model was used to investigate intervention with 3 doses of quercetin (low-dose, 50 mg/kg; medium-dose, 100 mg/kg; and high-dose, 200 mg/kg), the main active component of H. japonicum . Levels of serum biochemical indexes were measured by commercial kits, and the messenger RNA (mRNA) levels of markers of liver and mitochondrial function and oxidative stress were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). Results The main active ingredients of H. japonicum were quercetin, kaempferol, and tetramethoxyluteolin, and their key targets included prostaglandin G/H synthase 2 (PTGS2), B-cell lymphoma-2 (BCL2), cholesterol 7-alpha hydroxylase (CYP7A1), and farnesoid X receptor (FXR). Quercetin intervention promoted recovery from cholestatic hepatitis. Conclusions The findings from this research provide support for future research on the roles of quercetin, kaempferol, and tetramethoxyluteolin in human liver disease and the roles of the PTGS2, BCL2, CYP7A1, and FXR genes in cholestatic hepatitis.

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