Paeonia lactiflora Pall. ameliorates acetaminophen-induced oxidative stress and apoptosis via inhibiting the PKC-ERK pathway

Publication type:
Journal article
Metadata:
Autoren
  • Yubing Li
  • Xinyu Deng
  • Qichao Hu
  • Yuan Chen
  • Wenwen Zhang
  • Xuhua Qin
  • Feng Wei
  • Xiaohua Lu
  • Xiao Ma
  • Jinhao Zeng
  • Thomas Efferth
DOI
10.1016/j.jep.2024.118107
ISSN
0378-8741
Zeitschrift
Journal of Ethnopharmacology
Sprache
en
Artikelnummer
118107
Paginierung
118107 - 118107
Datum der Veröffentlichung
2024
Status
Accepted
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.jep.2024.118107
Datum der Datenerfassung
2024
Titel
Paeonia lactiflora Pall. ameliorates acetaminophen-induced oxidative stress and apoptosis via inhibiting the PKC-ERK pathway
Ausgabe der Zeitschrift
329

Data source: Crossref

Other metadata sources:
Abstract
<h4>Ethnopharmacological relevance</h4>Paeonia lactiflora Pall. (PLP), a traditional Chinese medicine, is recognized for its antioxidative and anti-apoptotic properties. Despite its potential medicinal value, the mechanisms underlying its efficacy have been less explored, particularly in alleviating acute liver injury (ALI) caused by excessive intake of acetaminophen (APAP).<h4>Aim of the study</h4>This study aims to elucidate the role and mechanisms of PLP in mitigating oxidative stress and apoptosis induced by APAP.<h4>Materials and methods</h4>C57BL/6 male mice were pre-treated with PLP for seven consecutive days, followed by the induction of ALI using APAP. Liver pathology was assessed using HE staining. Serum indicators, immunofluorescence (IF), immunohistochemical (IHC), and transmission electron microscopy were employed to evaluate levels of oxidative stress, ferroptosis and apoptosis. Differential expression proteins (DEPs) in the APAP-treated and PLP pre-treated groups were analyzed using quantitative proteomics. Subsequently, the potential mechanisms of PLP pre-treatment in treating ALI were validated using western blotting, molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) analysis.<h4>Results</h4>The UHPLC assay confirmed the presence of three compounds, i.e., albiflorin, paeoniflorin, and oxypaeoniflorin. Pre-treatment with PLP was observed to ameliorate liver tissue pathological damage through HE staining. Further confirmation of efficacy of PLP in alleviating APAP-induced liver injury and oxidative stress was established through liver function serum biochemical indicators, IF of reactive oxygen species (ROS) and IHC of glutathione peroxidase 4 (GPX4) detection. However, PLP did not demonstrate a significant effect in alleviating APAP-induced ferroptosis. Additionally, transmission electron microscopy and TUNEL staining indicated that PLP can mitigate hepatocyte apoptosis. PKC-ERK pathway was identified by proteomics, and subsequent molecular docking, molecular dynamics simulations, and SPR verified binding of the major components of PLP to ERK protein. Western blotting demonstrated that PLP suppressed protein kinase C (PKC) phosphorylation, blocking extracellular signal-regulated kinase (ERK) phosphorylation and inhibiting oxidative stress and cell apoptosis.<h4>Conclusion</h4>This study demonstrates that PLP possesses hepatoprotective abilities against APAP-induced ALI, primarily by inhibiting the PKC-ERK cascade to suppress oxidative stress and cell apoptosis.
Addresses
  • State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address: liyubing940@163.com.
Autoren
  • Yubing Li
  • Xinyu Deng
  • Qichao Hu
  • Yuan Chen
  • Wenwen Zhang
  • Xuhua Qin
  • Feng Wei
  • Xiaohua Lu
  • Xiao Ma
  • Jinhao Zeng
  • Thomas Efferth
DOI
10.1016/j.jep.2024.118107
eISSN
1872-7573
Externe Identifier
  • PubMed Identifier: 38599475
Funding acknowledgements
  • National Natural Science Foundation of China:
  • Sichuan Province Science and Technology Support Program:
Open access
false
ISSN
0378-8741
Zeitschrift
Journal of ethnopharmacology
Sprache
eng
Medium
Print-Electronic
Online publication date
2024
Paginierung
118107
Datum der Veröffentlichung
2024
Status
Published
Datum der Datenerfassung
2024
Titel
Paeonia lactiflora Pall. ameliorates acetaminophen-induced oxidative stress and apoptosis via inhibiting the PKC-ERK pathway.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
329

Data source: Europe PubMed Central

Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall. (PLP), a traditional Chinese medicine, is recognized for its antioxidative and anti-apoptotic properties. Despite its potential medicinal value, the mechanisms underlying its efficacy have been less explored, particularly in alleviating acute liver injury (ALI) caused by excessive intake of acetaminophen (APAP). AIM OF THE STUDY: This study aims to elucidate the role and mechanisms of PLP in mitigating oxidative stress and apoptosis induced by APAP. MATERIALS AND METHODS: C57BL/6 male mice were pre-treated with PLP for seven consecutive days, followed by the induction of ALI using APAP. Liver pathology was assessed using HE staining. Serum indicators, immunofluorescence (IF), immunohistochemical (IHC), and transmission electron microscopy were employed to evaluate levels of oxidative stress, ferroptosis and apoptosis. Differential expression proteins (DEPs) in the APAP-treated and PLP pre-treated groups were analyzed using quantitative proteomics. Subsequently, the potential mechanisms of PLP pre-treatment in treating ALI were validated using western blotting, molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) analysis. RESULTS: The UHPLC assay confirmed the presence of three compounds, i.e., albiflorin, paeoniflorin, and oxypaeoniflorin. Pre-treatment with PLP was observed to ameliorate liver tissue pathological damage through HE staining. Further confirmation of efficacy of PLP in alleviating APAP-induced liver injury and oxidative stress was established through liver function serum biochemical indicators, IF of reactive oxygen species (ROS) and IHC of glutathione peroxidase 4 (GPX4) detection. However, PLP did not demonstrate a significant effect in alleviating APAP-induced ferroptosis. Additionally, transmission electron microscopy and TUNEL staining indicated that PLP can mitigate hepatocyte apoptosis. PKC-ERK pathway was identified by proteomics, and subsequent molecular docking, molecular dynamics simulations, and SPR verified binding of the major components of PLP to ERK protein. Western blotting demonstrated that PLP suppressed protein kinase C (PKC) phosphorylation, blocking extracellular signal-regulated kinase (ERK) phosphorylation and inhibiting oxidative stress and cell apoptosis. CONCLUSION: This study demonstrates that PLP possesses hepatoprotective abilities against APAP-induced ALI, primarily by inhibiting the PKC-ERK cascade to suppress oxidative stress and cell apoptosis.
Date of acceptance
2024
Autoren
  • Yubing Li
  • Xinyu Deng
  • Qichao Hu
  • Yuan Chen
  • Wenwen Zhang
  • Xuhua Qin
  • Feng Wei
  • Xiaohua Lu
  • Xiao Ma
  • Jinhao Zeng
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/38599475
DOI
10.1016/j.jep.2024.118107
eISSN
1872-7573
Zeitschrift
J Ethnopharmacol
Schlüsselwörter
  • Acute liver injury
  • Hepatocyte apoptosis
  • Paeoniaceae
  • Phytotherapy
  • Proteomics
  • Reactive oxygen species
Sprache
eng
Country
Ireland
Paginierung
118107
PII
S0378-8741(24)00406-9
Datum der Veröffentlichung
2024
Status
Published online
Titel
Paeonia lactiflora Pall. ameliorates acetaminophen-induced oxidative stress and apoptosis via inhibiting the PKC-ERK pathway.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
329

Data source: PubMed

Beziehungen:
Property of

Tools