Cajaninstilbene acid (CSA) exerts cytoprotective effects against oxidative stress through the Nrf2-dependent antioxidant pathway

Autoren

Lu Liang
Meng Luo
Yujie Fu
Yuangang Zu
Wei Wang
Chengbo Gu
Chunjian Zhao
Chunying Li
Thomas Efferth

DOI

10.1016/j.toxlet.2013.03.008

ISSN

0378-4274

Ausgabe der Veröffentlichung

3

Zeitschrift

Toxicology Letters

Sprache

en

Paginierung

254 - 261

Datum der Veröffentlichung

2013

Status

Published

Herausgeber

Elsevier BV

Herausgeber URL

http://dx.doi.org/10.1016/j.toxlet.2013.03.008

Datum der Datenerfassung

2022

Titel

Cajaninstilbene acid (CSA) exerts cytoprotective effects against oxidative stress through the Nrf2-dependent antioxidant pathway

Ausgabe der Zeitschrift

219

Data source: Crossref

Abstract

Cajaninstilbene acid (CSA), an active compound separated from pigeon pea leaves, possesses the highly efficient antioxidant activities. Transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular oxidative stress. This study examined the role of Nrf2 in CSA-mediated antioxidant effects on human hepatocarcinoma (HepG2) cell line. The generation of reactive oxygen species (ROS) upon H2O2 and CSA treatment was lower than that of H2O2 alone. CSA activated Nrf2 as evaluated by Western blotting. A luciferase reporter assay also demonstrated that CSA-activated signaling resulted in the increased transcriptional activity of Nrf2 through binding to the antioxidant response element (ARE) enhancer sequence. Our study indicated that treatment of HepG2 cells with CSA induces Nrf2-dependent ARE activity and gene expression of heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase modifier subunits by activation of PI3K/AKT, ERK and JNK signaling pathways. Inhibition of Nrf2 by siRNA reduced CSA-induced upregulation of these Nrf2-related enzymes. These results suggest that the Nrf2/ARE pathway plays an important role in the regulation of CSA-mediated antioxidant effects in HepG2 cells.

Addresses

State Engineering Laboratory for Bio-Resource Eco-Utilization, Northeast Forestry University, Harbin 150040, PR China.

Autoren

Lu Liang
Meng Luo
Yujie Fu
Yuangang Zu
Wei Wang
Chengbo Gu
Chunjian Zhao
Chunying Li
Thomas Efferth
Thomas Efferth

DOI

10.1016/j.toxlet.2013.03.008

eISSN

1879-3169

Externe Identifier

PubMed Identifier: 23535287

Funding acknowledgements

Program for Importation of International Advanced Forestry Science and Technology, National Forestry Bureau: 2012-4-06
Project for Distinguished Teacher Abroad, Chinese Ministry of Education: MS2010DBLY031
Special Fund of Forestry Industrial Research for Public Welfare of China: 201004040
Heilongjiang Province Science Foundation for Excellent Youths: JC200704

Open access

false

ISSN

0378-4274

Ausgabe der Veröffentlichung

3

Zeitschrift

Toxicology letters

Schlüsselwörter

Humans
Salicylates
Stilbenes
NAD(P)H Dehydrogenase (Quinone)
Antioxidants
Blotting, Western
Signal Transduction
Oxidative Stress
Cytoprotection
NF-E2-Related Factor 2
Heme Oxygenase-1
Hep G2 Cells
Antioxidant Response Elements

Sprache

eng

Medium

Print-Electronic

Online publication date

2013

Paginierung

254 - 261

Datum der Veröffentlichung

2013

Status

Published

Datum der Datenerfassung

2013

Titel

Cajaninstilbene acid (CSA) exerts cytoprotective effects against oxidative stress through the Nrf2-dependent antioxidant pathway.

Sub types

Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

219

Data source: Europe PubMed Central

Abstract

Cajaninstilbene acid (CSA), an active compound separated from pigeon pea leaves, possesses the highly efficient antioxidant activities. Transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular oxidative stress. This study examined the role of Nrf2 in CSA-mediated antioxidant effects on human hepatocarcinoma (HepG2) cell line. The generation of reactive oxygen species (ROS) upon H2O2 and CSA treatment was lower than that of H2O2 alone. CSA activated Nrf2 as evaluated by Western blotting. A luciferase reporter assay also demonstrated that CSA-activated signaling resulted in the increased transcriptional activity of Nrf2 through binding to the antioxidant response element (ARE) enhancer sequence. Our study indicated that treatment of HepG2 cells with CSA induces Nrf2-dependent ARE activity and gene expression of heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase modifier subunits by activation of PI3K/AKT, ERK and JNK signaling pathways. Inhibition of Nrf2 by siRNA reduced CSA-induced upregulation of these Nrf2-related enzymes. These results suggest that the Nrf2/ARE pathway plays an important role in the regulation of CSA-mediated antioxidant effects in HepG2 cells.

Date of acceptance

2013

Autoren

Lu Liang
Meng Luo
Yujie Fu
Yuangang Zu
Wei Wang
Chengbo Gu
Chunjian Zhao
Chunying Li
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/23535287

DOI

10.1016/j.toxlet.2013.03.008

eISSN

1879-3169

Ausgabe der Veröffentlichung

3

Zeitschrift

Toxicol Lett

Schlüsselwörter

Antioxidant Response Elements
Antioxidants
Blotting, Western
Cytoprotection
Heme Oxygenase-1
Hep G2 Cells
Humans
NAD(P)H Dehydrogenase (Quinone)
NF-E2-Related Factor 2
Oxidative Stress
Salicylates
Signal Transduction
Stilbenes

Sprache

eng

Country

Netherlands

Paginierung

254 - 261

PII

S0378-4274(13)00106-9

Datum der Veröffentlichung

2013

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2013

Titel

Cajaninstilbene acid (CSA) exerts cytoprotective effects against oxidative stress through the Nrf2-dependent antioxidant pathway.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

219

Data source: PubMed

Cajaninstilbene acid (CSA) exerts cytoprotective effects against oxidative stress through the Nrf2-dependent antioxidant pathway

Tools