Abstract
Because induction of phase II detoxification enzyme is important for chemoprevention, we study the effects of Indigofera suffruticosa Mill, a medicinal herb, on the expression of π class of glutathione S-transferase (GSTP) and NAD(P)H: quinone oxidoreductase 1 (NQO1) in rat Clone 9 liver cells. Both water and ethanolic extracts of I. suffruticosa significantly increased the expression and enzyme activities of GSTP and NQO1. I. suffruticosa extracts up-regulated GSTP promoter activity and the binding affinity of nuclear factor erythroid 2-related factor 2 (Nrf2) with the GSTP enhancer I oligonucleotide. Moreover, I. suffruticosa extracts increased nuclear Nrf2 accumulation as well as ARE transcriptional activity. The level of phospho-ERK was augmented by I. suffruticosa extracts, and the ERK inhibitor PD98059 abolished the I. suffruticosa extract-induced ERK activation and GSTP and NQO-1 expression. Moreover, I. suffruticosa extracts, especially the ethanolic extract increased the glutathione level in mouse liver and red blood cells as well as Clone 9 liver cells. The efficacy of I. suffruticosa extracts in induction of phase II detoxification enzymes and glutathione content implies that I. suffruticosa could be considered as a potential chemopreventive agent.
Abbreviations
AP-1activator protein-1AREantioxidant response elementDMSOdimethylsulfoxideERK1/2extracellular signal-regulated kinase 1/2GPEIGSTP enhancer IGSTglutathione S-transferaseGSTPπ class of glutathione S-transferaseHPLChigh-performance liquid chromatographyKeap1Kelch-like ECH-associated protein 1MTT3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromideNQO1NAD(P)H quinone oxidoreductase 1Nrf2nuclear factor erythroid 2-related factor 2PARPpoly ADP-ribose polymerasePMSFphenylmethylsulfonyl fluorideRT-PCRreverse transcriptase polymerase chain reactionTRE-like12-O-tetra-decanoyl-phorbol-13-acetated response-like
