Aucubin as a natural potential anti-acute hepatitis candidate: Inhibitory potency and hepatoprotective mechanism

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Han Huang
  • Yuan-Hang Chang
  • Jian Xu
  • Hai-Yan Ni
  • Heng Zhao
  • Bo-Wen Zhai
  • Thomas Efferth
  • Cheng-Bo Gu
  • Yu-Jie Fu
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000820087200001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.phymed.2022.154170
eISSN
1618-095X
Externe Identifier
  • Clarivate Analytics Document Solution ID: 2P9YN
  • PubMed Identifier: 35609387
ISSN
0944-7113
Zeitschrift
PHYTOMEDICINE
Schlüsselwörter
  • Aucubin
  • Acute hepatitis
  • Network pharmacology
  • Molecular simulation
  • Anti-inflammatory
Artikelnummer
ARTN 154170
Datum der Veröffentlichung
2022
Status
Published
Titel
Aucubin as a natural potential anti-acute hepatitis candidate: Inhibitory potency and hepatoprotective mechanism
Sub types
  • Article
Ausgabe der Zeitschrift
102

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Autoren
  • Han Huang
  • Yuan-Hang Chang
  • Jian Xu
  • Hai-Yan Ni
  • Heng Zhao
  • Bo-Wen Zhai
  • Thomas Efferth
  • Cheng-Bo Gu
  • Yu-Jie Fu
DOI
10.1016/j.phymed.2022.154170
ISSN
0944-7113
Zeitschrift
Phytomedicine
Sprache
en
Artikelnummer
154170
Paginierung
154170 - 154170
Datum der Veröffentlichung
2022
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.phymed.2022.154170
Datum der Datenerfassung
2024
Titel
Aucubin as a natural potential anti-acute hepatitis candidate: Inhibitory potency and hepatoprotective mechanism
Ausgabe der Zeitschrift
102

Datenquelle: Crossref

Abstract
<h4>Background</h4>Hepatic inflammation can substantially impact the development of acute hepatitis. It is a pressing need to identify and exploit novel therapeutic targets as well as effective drug therapies against acute hepatitis. Aucubin (AU) is one of the main active components extracted from the leaves of Eucommia ulmoides and possesses significant anti-inflammatory and antioxidant activities. However, the protective effect and mechanism of AU on acute hepatitis have not been reported yet.<h4>Purpose</h4>This study aims to investigate the protective effect of AU on LPS-induced acute hepatitis and the mechanism of action.<h4>Methods</h4>The limma package was used to analyze differentially expressed genes (DEGs) between LPS-induced acute hepatitis and normal groups based on Gene Expression Omnibus (GEO) microarray data. Network pharmacology predicted targets for AU therapy against acute hepatitis, and Gene Ontology (GO) enrichment analysis of the biological processes involved in these targets. The key pathways were analyzed by protein-protein interaction, KEGG (Kyoto Encyclopedia of Genes and Genomes), and GSEA (Gene Set Enrichment Analysis) enrichment. The important interaction targets between AU and key pathways were evaluated by molecular simulation. The in silico predicted mechanism was verified based on in vitro and in vivo experiments.<h4>Results</h4>A total of 116 intersection targets between AU prediction targets and differentially expressed genes were identified. They were functionally involved in the imbalance of "inflammation-anti-inflammation" and "oxidation-antioxidation" systems in the process of LPS-induced cases. In vitro experiments revealed that AU reduced inflammation in LPS-induced HepG2 cells by reducing the inflammatory cytokines TNF-α, IL-6, as well as iNOS enzyme activity levels. In addition, LPS-induced oxidative stress can be alleviated by AU via adjusting the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Malone dialdehyde (MDA) and reactive oxygen species (ROS). Protein-protein interaction and GSEA results showed that AU might exert anti-inflammatory effects mainly through the STAT3/NF-κB signal pathway. Molecular dynamics simulation as well as in vivo tests further demonstrated AU restrained nuclear transfer of NF-κB (P65), probably through reducing phosphorylation of STAT3. In addition, AU appears to reduce oxidative stress by upregulating NRF2/HO-1.<h4>Conclusion</h4>We explored potential targets and signal pathways of AU in inhibiting acute hepatitis. AU exerted anti-inflammatory and antioxidant activities and may be a useful candidate drug for the treatment of acute hepatitis.
Addresses
  • Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China.
Autoren
  • Han Huang
  • Yuan-Hang Chang
  • Jian Xu
  • Hai-Yan Ni
  • Heng Zhao
  • Bo-Wen Zhai
  • Thomas Efferth
  • Cheng-Bo Gu
  • Yu-Jie Fu
DOI
10.1016/j.phymed.2022.154170
eISSN
1618-095X
Externe Identifier
  • PubMed Identifier: 35609387
Open access
false
ISSN
0944-7113
Zeitschrift
Phytomedicine : international journal of phytotherapy and phytopharmacology
Schlüsselwörter
  • Humans
  • Hepatitis
  • Inflammation
  • Lipopolysaccharides
  • NF-kappa B
  • Anti-Inflammatory Agents
  • Antioxidants
  • Oxidative Stress
  • NF-E2-Related Factor 2
  • Iridoid Glucosides
Sprache
eng
Medium
Print-Electronic
Online publication date
2022
Paginierung
154170
Datum der Veröffentlichung
2022
Status
Published
Datum der Datenerfassung
2022
Titel
Aucubin as a natural potential anti-acute hepatitis candidate: Inhibitory potency and hepatoprotective mechanism.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
102

Datenquelle: Europe PubMed Central

Abstract
BACKGROUND: Hepatic inflammation can substantially impact the development of acute hepatitis. It is a pressing need to identify and exploit novel therapeutic targets as well as effective drug therapies against acute hepatitis. Aucubin (AU) is one of the main active components extracted from the leaves of Eucommia ulmoides and possesses significant anti-inflammatory and antioxidant activities. However, the protective effect and mechanism of AU on acute hepatitis have not been reported yet. PURPOSE: This study aims to investigate the protective effect of AU on LPS-induced acute hepatitis and the mechanism of action. METHODS: The limma package was used to analyze differentially expressed genes (DEGs) between LPS-induced acute hepatitis and normal groups based on Gene Expression Omnibus (GEO) microarray data. Network pharmacology predicted targets for AU therapy against acute hepatitis, and Gene Ontology (GO) enrichment analysis of the biological processes involved in these targets. The key pathways were analyzed by protein-protein interaction, KEGG (Kyoto Encyclopedia of Genes and Genomes), and GSEA (Gene Set Enrichment Analysis) enrichment. The important interaction targets between AU and key pathways were evaluated by molecular simulation. The in silico predicted mechanism was verified based on in vitro and in vivo experiments. RESULTS: A total of 116 intersection targets between AU prediction targets and differentially expressed genes were identified. They were functionally involved in the imbalance of "inflammation-anti-inflammation" and "oxidation-antioxidation" systems in the process of LPS-induced cases. In vitro experiments revealed that AU reduced inflammation in LPS-induced HepG2 cells by reducing the inflammatory cytokines TNF-α, IL-6, as well as iNOS enzyme activity levels. In addition, LPS-induced oxidative stress can be alleviated by AU via adjusting the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Malone dialdehyde (MDA) and reactive oxygen species (ROS). Protein-protein interaction and GSEA results showed that AU might exert anti-inflammatory effects mainly through the STAT3/NF-κB signal pathway. Molecular dynamics simulation as well as in vivo tests further demonstrated AU restrained nuclear transfer of NF-κB (P65), probably through reducing phosphorylation of STAT3. In addition, AU appears to reduce oxidative stress by upregulating NRF2/HO-1. CONCLUSION: We explored potential targets and signal pathways of AU in inhibiting acute hepatitis. AU exerted anti-inflammatory and antioxidant activities and may be a useful candidate drug for the treatment of acute hepatitis.
Date of acceptance
2022
Autoren
  • Han Huang
  • Yuan-Hang Chang
  • Jian Xu
  • Hai-Yan Ni
  • Heng Zhao
  • Bo-Wen Zhai
  • Thomas Efferth
  • Cheng-Bo Gu
  • Yu-Jie Fu
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/35609387
DOI
10.1016/j.phymed.2022.154170
eISSN
1618-095X
Zeitschrift
Phytomedicine
Schlüsselwörter
  • Acute hepatitis
  • Anti-inflammatory
  • Aucubin
  • Molecular simulation
  • Network pharmacology
  • Anti-Inflammatory Agents
  • Antioxidants
  • Hepatitis
  • Humans
  • Inflammation
  • Iridoid Glucosides
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Oxidative Stress
Sprache
eng
Country
Germany
Paginierung
154170
PII
S0944-7113(22)00248-3
Datum der Veröffentlichung
2022
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Titel
Aucubin as a natural potential anti-acute hepatitis candidate: Inhibitory potency and hepatoprotective mechanism.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
102

Datenquelle: PubMed

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