Induction of antioxidant and phase 2 drug-metabolizing enzymes by falcarindiol isolated from Notopterygium incisum extract, which activates the Nrf2/ARE pathway, leads to cytoprotection against oxidative and electrophilic stress

Tomokazu Ohnuma; Takao Komatsu; Shinji Nakayama; Takahito Nishiyama; Kenichiro Ogura; Akira Hiratsuka

doi:10.1016/j.abb.2009.06.006

Induction of antioxidant and phase 2 drug-metabolizing enzymes by falcarindiol isolated from Notopterygium incisum extract, which activates the Nrf2/ARE pathway, leads to cytoprotection against oxidative and electrophilic stress

Arch Biochem Biophys. 2009 Aug 1;488(1):34-41. doi: 10.1016/j.abb.2009.06.006. Epub 2009 Jun 13.

Authors

Tomokazu Ohnuma¹, Takao Komatsu, Shinji Nakayama, Takahito Nishiyama, Kenichiro Ogura, Akira Hiratsuka

Affiliation

¹ Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji-shi, Tokyo, Japan.

PMID: 19527678
DOI: 10.1016/j.abb.2009.06.006

Abstract

In the present study, we isolated falcarindiol from Notopterygium incisum and investigated the effect of falcarindiol on the expression of antioxidant enzymes (AOEs), such as catalase, and phase 2 drug-metabolizing enzymes (DMEs), such as glutathione S-transferase and NAD(P)H:quinone oxidoreductase 1, in a cultured cell line from normal rat liver, Clone 9 cells. Exposure of Clone 9 cells to falcarindiol resulted in the significant induction of AOEs and phase 2 DMEs. Western blot analysis and transfection studies using a luciferase reporter construct demonstrated that the induction of AOEs and phase 2 DMEs by falcarindiol was caused through the Nrf2/ARE (nuclear factor-E2-related factor 2/antioxidant response element) pathway. Pretreatment of cells with falcarindiol accelerated the detoxification of a potentially toxic quinone (menadione) and mitigated menadione-induced cytotoxicity. We found that falcarindiol was a novel inducer of AOEs and phase 2 DMEs and falcarindiol might exhibit chemopreventive activity.

MeSH terms

Animals
Antioxidants / metabolism
Apiaceae / chemistry*
Cell Death / drug effects
Clone Cells / drug effects
Clone Cells / enzymology
Clone Cells / metabolism
Cytoprotection / drug effects
Cytotoxins / metabolism
Cytotoxins / toxicity
Diynes / analysis
Diynes / isolation & purification
Diynes / pharmacology*
Electrons
Enzyme Induction / drug effects
Enzymes / biosynthesis*
Enzymes / genetics
Enzymes / metabolism
Fatty Alcohols / analysis
Fatty Alcohols / isolation & purification
Fatty Alcohols / pharmacology*
Gene Expression Regulation, Enzymologic / drug effects
Heme Oxygenase-1 / genetics
Humans
Metabolic Detoxication, Phase II
NF-E2-Related Factor 2 / genetics
NF-E2-Related Factor 2 / metabolism*
Oxidative Stress / drug effects*
Plant Extracts / analysis
Plant Extracts / isolation & purification
Plant Extracts / pharmacology
RNA, Messenger / genetics
RNA, Messenger / metabolism
Rats
Response Elements*
Signal Transduction / drug effects*
Vitamin K 3 / metabolism
Vitamin K 3 / toxicity

Substances

Antioxidants
Cytotoxins
Diynes
Enzymes
Fatty Alcohols
NF-E2-Related Factor 2
Plant Extracts
RNA, Messenger
falcarindiol
Vitamin K 3
Heme Oxygenase-1