A phase II detoxification enzyme inducer from lemongrass: Identification of citral and involvement of electrophilic reaction in the enzyme induction

Yoshimasa Nakamura, Masaaki Miyamoto, Akira Murakami, Hajime Ohigashi, Toshihiko Osawa, Koji Uchida

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

We have developed a simple system for the sensitive detection and measurement of glutathione S-transferase (GST) activity that detoxifies polycyclic aromatic hydrocarbons using the cultured rat normal liver epithelial cell line, RL34 cells. Citral (3,7-dimethyl-2,6-octadienal) was isolated from the methanol extract of lemongrass (Cymbopogon citratus) and identified as a novel inducer of GST. Citral, a mixture of the two stereoisomers geranial and neral, dose- and time-dependently induced the total and pi-class-specific activities of GST. The structure-activity relationship study revealed that geranial, an E-isomer, was mainly responsible for the inducing activity of citral mixture and the aldehyde group conjugated with a trans-double bond is an essential structural factor. The data were consistent with the in vitro observation that both glutathione (GSH) and protein thiol quickly and specifically reacted with the active isomer geranial, but not neral. Pretreatment of the cells with diethyl maleate significantly enhanced not only the basal activity but also the citral-stimulated activity of GST, while pretreatment with N-acetyl-cysteine inhibited it. Moreover, the treatment of RL 34 cells with geranial for 30min significantly attenuated the intracellular GSH level, while application for 18h enhanced it. These results strongly suggested that the electrophilic property characterized by the reactivity with intracellular nucleophiles including protein thiol or glutathione (GSH) plays an important role in the induction of GST. The present study also implied the antioxidant role of GST induction by citral in mouse skin, providing a new insight into skin cancer prevention.

Original languageEnglish
Pages (from-to)593-600
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume302
Issue number3
DOIs
Publication statusPublished - Mar 14 2003
Externally publishedYes

Fingerprint

citral
Phase II Metabolic Detoxication
Cymbopogon
Detoxification
Enzyme Induction
Glutathione Transferase
Enzymes
diethyl maleate
Sulfhydryl Compounds
Isomers
Glutathione
Skin
Acetylcysteine

Keywords

  • α,β-Unsaturated carbonyl
  • Antioxidant
  • Cancer prevention
  • Citral
  • Detoxification
  • Electrophile
  • Glutathione
  • Glutathione S-transferase
  • RL34

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

A phase II detoxification enzyme inducer from lemongrass : Identification of citral and involvement of electrophilic reaction in the enzyme induction. / Nakamura, Yoshimasa; Miyamoto, Masaaki; Murakami, Akira; Ohigashi, Hajime; Osawa, Toshihiko; Uchida, Koji.

In: Biochemical and Biophysical Research Communications, Vol. 302, No. 3, 14.03.2003, p. 593-600.

Research output: Contribution to journalArticle

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