Plant Extracts of the Family Lauraceae

A Potential Resource for Chemopreventive Agents that Activate the Nuclear Factor-Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway

Tao Shen, Xue Mei Chen, Bryan Harder, Min Long, Xiao Ning Wang, Hong Xiang Lou, Georg T. Wondark, Dong Mei Ren, Donna Zhang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Cells and tissues counteract insults from exogenous or endogenous carcinogens through the expression of genes encoding antioxidants and phase II detoxifying enzymes regulated by antioxidant response element promoter regions. Nuclear factor-erythroid 2-related factor 2 plays a key role in regulating the antioxidant response elements-target gene expression. Hence, the Nrf2/ARE pathway represents a vital cellular defense mechanism against damage caused by oxidative stress and xenobiotics, and is recognized as a potential molecular target for discovering chemopreventive agents. Using a stable antioxidant response element luciferase reporter cell line derived from human breast cancer MDA-MB-231 cells combined with a 96-well high-throughput screening system, we have identified a series of plant extracts from the family Lauraceae that harbor Nrf2-inducing effects. These extracts, including Litsea garrettii (ZK-08), Cinnamomum chartophyllum (ZK-02), C. mollifolium (ZK-04), C. camphora var. linaloolifera (ZK-05), and C. burmannii (ZK-10), promoted nuclear translocation of Nrf2, enhanced protein expression of Nrf2 and its target genes, and augmented intracellular glutathione levels. Cytoprotective activity of these extracts against two electrophilic toxicants, sodium arsenite and H2O 2, was investigated. Treatment of human bronchial epithelial cells with extracts of ZK-02, ZK-05, and ZK-10 significantly improved cell survival in response to sodium arsenite and H2O2, while ZK-08 showed a protective effect against only H2O2. Importantly, their protective effects against insults from both sodium arsenite and H 2O2 were Nrf2-dependent. Therefore, our data provide evidence that the selected plants from the family Lauraceae are potential sources for chemopreventive agents targeting the Nrf2/ARE pathway.

Original languageEnglish (US)
Pages (from-to)426-434
Number of pages9
JournalPlanta Medica
Volume80
Issue number5
DOIs
StatePublished - 2014

Fingerprint

Lauraceae
Antioxidant Response Elements
Plant Extracts
Litsea
Cinnamomum
Cells
Gene Expression
Gene encoding
Oxidative stress
Xenobiotics
Ports and harbors
Cell Extracts
Luciferases
Genetic Promoter Regions
Gene expression
Carcinogens
Glutathione
Cell Survival
Screening
Oxidative Stress

Keywords

  • chemoprevention
  • Cinnamomum
  • Lauraceae
  • Litsea
  • Nrf2/ARE pathway
  • plant extracts

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Analytical Chemistry
  • Organic Chemistry
  • Molecular Medicine
  • Complementary and alternative medicine
  • Medicine(all)

Cite this

Plant Extracts of the Family Lauraceae : A Potential Resource for Chemopreventive Agents that Activate the Nuclear Factor-Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway. / Shen, Tao; Chen, Xue Mei; Harder, Bryan; Long, Min; Wang, Xiao Ning; Lou, Hong Xiang; Wondark, Georg T.; Ren, Dong Mei; Zhang, Donna.

In: Planta Medica, Vol. 80, No. 5, 2014, p. 426-434.

Research output: Contribution to journalArticle

Shen, Tao ; Chen, Xue Mei ; Harder, Bryan ; Long, Min ; Wang, Xiao Ning ; Lou, Hong Xiang ; Wondark, Georg T. ; Ren, Dong Mei ; Zhang, Donna. / Plant Extracts of the Family Lauraceae : A Potential Resource for Chemopreventive Agents that Activate the Nuclear Factor-Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway. In: Planta Medica. 2014 ; Vol. 80, No. 5. pp. 426-434.
@article{d29e54a169574c81a01a4c7d92510200,
title = "Plant Extracts of the Family Lauraceae: A Potential Resource for Chemopreventive Agents that Activate the Nuclear Factor-Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway",
abstract = "Cells and tissues counteract insults from exogenous or endogenous carcinogens through the expression of genes encoding antioxidants and phase II detoxifying enzymes regulated by antioxidant response element promoter regions. Nuclear factor-erythroid 2-related factor 2 plays a key role in regulating the antioxidant response elements-target gene expression. Hence, the Nrf2/ARE pathway represents a vital cellular defense mechanism against damage caused by oxidative stress and xenobiotics, and is recognized as a potential molecular target for discovering chemopreventive agents. Using a stable antioxidant response element luciferase reporter cell line derived from human breast cancer MDA-MB-231 cells combined with a 96-well high-throughput screening system, we have identified a series of plant extracts from the family Lauraceae that harbor Nrf2-inducing effects. These extracts, including Litsea garrettii (ZK-08), Cinnamomum chartophyllum (ZK-02), C. mollifolium (ZK-04), C. camphora var. linaloolifera (ZK-05), and C. burmannii (ZK-10), promoted nuclear translocation of Nrf2, enhanced protein expression of Nrf2 and its target genes, and augmented intracellular glutathione levels. Cytoprotective activity of these extracts against two electrophilic toxicants, sodium arsenite and H2O 2, was investigated. Treatment of human bronchial epithelial cells with extracts of ZK-02, ZK-05, and ZK-10 significantly improved cell survival in response to sodium arsenite and H2O2, while ZK-08 showed a protective effect against only H2O2. Importantly, their protective effects against insults from both sodium arsenite and H 2O2 were Nrf2-dependent. Therefore, our data provide evidence that the selected plants from the family Lauraceae are potential sources for chemopreventive agents targeting the Nrf2/ARE pathway.",
keywords = "chemoprevention, Cinnamomum, Lauraceae, Litsea, Nrf2/ARE pathway, plant extracts",
author = "Tao Shen and Chen, {Xue Mei} and Bryan Harder and Min Long and Wang, {Xiao Ning} and Lou, {Hong Xiang} and Wondark, {Georg T.} and Ren, {Dong Mei} and Donna Zhang",
year = "2014",
doi = "10.1055/s-0034-1368197",
language = "English (US)",
volume = "80",
pages = "426--434",
journal = "Planta Medica",
issn = "0032-0943",
publisher = "Georg Thieme Verlag",
number = "5",

}

TY - JOUR

T1 - Plant Extracts of the Family Lauraceae

T2 - A Potential Resource for Chemopreventive Agents that Activate the Nuclear Factor-Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway

AU - Shen, Tao

AU - Chen, Xue Mei

AU - Harder, Bryan

AU - Long, Min

AU - Wang, Xiao Ning

AU - Lou, Hong Xiang

AU - Wondark, Georg T.

AU - Ren, Dong Mei

AU - Zhang, Donna

PY - 2014

Y1 - 2014

N2 - Cells and tissues counteract insults from exogenous or endogenous carcinogens through the expression of genes encoding antioxidants and phase II detoxifying enzymes regulated by antioxidant response element promoter regions. Nuclear factor-erythroid 2-related factor 2 plays a key role in regulating the antioxidant response elements-target gene expression. Hence, the Nrf2/ARE pathway represents a vital cellular defense mechanism against damage caused by oxidative stress and xenobiotics, and is recognized as a potential molecular target for discovering chemopreventive agents. Using a stable antioxidant response element luciferase reporter cell line derived from human breast cancer MDA-MB-231 cells combined with a 96-well high-throughput screening system, we have identified a series of plant extracts from the family Lauraceae that harbor Nrf2-inducing effects. These extracts, including Litsea garrettii (ZK-08), Cinnamomum chartophyllum (ZK-02), C. mollifolium (ZK-04), C. camphora var. linaloolifera (ZK-05), and C. burmannii (ZK-10), promoted nuclear translocation of Nrf2, enhanced protein expression of Nrf2 and its target genes, and augmented intracellular glutathione levels. Cytoprotective activity of these extracts against two electrophilic toxicants, sodium arsenite and H2O 2, was investigated. Treatment of human bronchial epithelial cells with extracts of ZK-02, ZK-05, and ZK-10 significantly improved cell survival in response to sodium arsenite and H2O2, while ZK-08 showed a protective effect against only H2O2. Importantly, their protective effects against insults from both sodium arsenite and H 2O2 were Nrf2-dependent. Therefore, our data provide evidence that the selected plants from the family Lauraceae are potential sources for chemopreventive agents targeting the Nrf2/ARE pathway.

AB - Cells and tissues counteract insults from exogenous or endogenous carcinogens through the expression of genes encoding antioxidants and phase II detoxifying enzymes regulated by antioxidant response element promoter regions. Nuclear factor-erythroid 2-related factor 2 plays a key role in regulating the antioxidant response elements-target gene expression. Hence, the Nrf2/ARE pathway represents a vital cellular defense mechanism against damage caused by oxidative stress and xenobiotics, and is recognized as a potential molecular target for discovering chemopreventive agents. Using a stable antioxidant response element luciferase reporter cell line derived from human breast cancer MDA-MB-231 cells combined with a 96-well high-throughput screening system, we have identified a series of plant extracts from the family Lauraceae that harbor Nrf2-inducing effects. These extracts, including Litsea garrettii (ZK-08), Cinnamomum chartophyllum (ZK-02), C. mollifolium (ZK-04), C. camphora var. linaloolifera (ZK-05), and C. burmannii (ZK-10), promoted nuclear translocation of Nrf2, enhanced protein expression of Nrf2 and its target genes, and augmented intracellular glutathione levels. Cytoprotective activity of these extracts against two electrophilic toxicants, sodium arsenite and H2O 2, was investigated. Treatment of human bronchial epithelial cells with extracts of ZK-02, ZK-05, and ZK-10 significantly improved cell survival in response to sodium arsenite and H2O2, while ZK-08 showed a protective effect against only H2O2. Importantly, their protective effects against insults from both sodium arsenite and H 2O2 were Nrf2-dependent. Therefore, our data provide evidence that the selected plants from the family Lauraceae are potential sources for chemopreventive agents targeting the Nrf2/ARE pathway.

KW - chemoprevention

KW - Cinnamomum

KW - Lauraceae

KW - Litsea

KW - Nrf2/ARE pathway

KW - plant extracts

UR - http://www.scopus.com/inward/record.url?scp=84898022069&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84898022069&partnerID=8YFLogxK

U2 - 10.1055/s-0034-1368197

DO - 10.1055/s-0034-1368197

M3 - Article

VL - 80

SP - 426

EP - 434

JO - Planta Medica

JF - Planta Medica

SN - 0032-0943

IS - 5

ER -