Synthesis and Nrf2-inducing activity of the isothiocyanates iberverin, iberin and cheirolin

被引：32

作者：

Ernst, Insa M. A. ^{[1
]}

Palani, Kalpana ^{[1
]}

Esatbeyoglu, Tuba ^{[1
]}

Schwarz, Karin ^{[1
]}

Rimbach, Gerald ^{[1
]}

机构：

[1] Univ Kiel, Inst Human Nutr & Food Sci, D-24118 Kiel, Germany

来源：

PHARMACOLOGICAL RESEARCH | 2013年 / 70卷 / 01期

关键词：

Iberverin; Iberin; Cheirolin; Chemical isothiocyanate synthesis; Nrf2; INDUCTION; ENZYMES; NRF2; SULFORAPHANE; BROCCOLI; SEEDS; BIOTRANSFORMATION; IDENTIFICATION; HYDROLYSIS; EXPRESSION;

D O I：

10.1016/j.phrs.2013.01.011

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Numerous studies have reported a potent induction of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent gene expression by the isothiocyanate sulforaphane. However, little is known regarding the Nrf2-inducing activities of the lower structure-related sulforaphane homologues, such as iberverin, iberin and cheirolin, which exhibit different sulfur oxidation states. Therefore, in this study we synthesized the isothiocyanates iberverin, iberin and cheirolin with a high yield and purity and determined their Nrf2-inducing activity in NIH3T3 fibroblasts. Iberverin, iberin and cheirolin significantly induced Nrf2 nuclear translocation. The increase in nuclear Nrf2 levels was accompanied by a significant increase in heme oxygenase 1 (HO-1) and gamma-glutamylcysteine synthetase (gamma GCS) mRNA and protein levels. Overall, iberverin, iberin and cheirolin exhibited a similar potency to sulforaphane in inducing Nrf2-dependent gene-expression. Furthermore, our data suggest that the induction of Nrf2 by iberverin, iberin and cheirolin may have occurred via an extracellular signal-related kinase (ERK)-dependent signal-transduction pathway. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：155 / 162

页数：8

共 39 条

[1]

APPLEGATE LA, 1991, CANCER RES, V51, P974

[2] Reactive oxygen species and their detoxification in healing skin wounds [J].

auf dem Keller, Ulrich ;

Kuemin, Angelika ;

Braun, Susanne ;

Werner, Sabine .

JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS, 2006, 11 (01) :106-111

[3] Hormetics: Dietary Triggers of an Adaptive Stress Response [J].

Birringer, Marc .

PHARMACEUTICAL RESEARCH, 2011, 28 (11) :2680-2694

[4] TOXICITY DETERMINED INVITRO BY MORPHOLOGICAL ALTERATIONS AND NEUTRAL RED ABSORPTION [J].

BORENFREUND, E ;

PUERNER, JA .

TOXICOLOGY LETTERS, 1985, 24 (2-3) :119-124

[5] A facile and efficient synthesis of 14C-labelled sulforaphane [J].

D'Souza, CA ;

Amin, S ;

Desai, D .

JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 2003, 46 (09) :851-859

[6] GLUCOSINOLATE COMPOSITION OF SEEDS FROM 297 SPECIES OF WILD PLANTS [J].

DAXENBICHLER, ME ;

SPENCER, GF ;

CARLSON, DG ;

ROSE, GB ;

BRINKER, AM ;

POWELL, RG .

PHYTOCHEMISTRY, 1991, 30 (08) :2623-2638

[7] Allyl-, butyl- and phenylethyl-isothiocyanate activate Nrf2 in cultured fibroblasts [J].

Ernst, Insa M. A. ;

Wagner, Anika E. ;

Schuemann, Christine ;

Storm, Niels ;

Hoeppner, Wolfgang ;

Doering, Frank ;

Stocker, Achim ;

Rimbach, Gerald .

PHARMACOLOGICAL RESEARCH, 2011, 63 (03) :233-240

[8] The chemical diversity and distribution of glucosinolates and isothiocyanates among plants [J].

Fahey, JW ;

Zalcmann, AT ;

Talalay, P .

PHYTOCHEMISTRY, 2001, 56 (01) :5-51

[9]

Getahun SM, 1999, CANCER EPIDEM BIOMAR, V8, P447

[10] Repeated intake of broccoli does not lead to higher plasma levels of sulforaphane in human volunteers [J].

Hanlon, Natalya ;

Coldham, Nick ;

Gielbert, Adriana ;

Sauer, Maurice J. ;

Ioannides, Costas .

CANCER LETTERS, 2009, 284 (01) :15-20

← 1 2 3 4 →