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Nrf2‐mediated induction of detoxifying enzymes by alantolactone present in Inula helenium
Author(s) -
Seo Ji Yeon,
Lim Soon Sung,
Kim Ju Ryoung,
Lim JiSun,
Ha Young Ran,
Lee In Ae,
Kim Eun Ji,
Park Jung Han Yoon,
Kim JongSang
Publication year - 2008
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.2521
Subject(s) - glutathione , inula , enzyme , antioxidant , biochemistry , glutathione reductase , reductase , glutathione s transferase , luciferase , chemistry , phosphatidylinositol , microbiology and biotechnology , kinase , biology , transfection , gene , glutathione peroxidase , medicine , alternative medicine , traditional chinese medicine , pathology
Our previous study showed that a methanol extract of Inula helenium had the potential to induce detoxifying enzymes such as quinone reductase (QR) and glutathione S ‐transferase (GST) activity. In this study the methanol extract was further fractionated using silica gel chromatography and vacuum liquid chromatography, to yield pure compounds alantolactone and isoalantolactone as QR inducers. Alantolactone caused a dose‐dependent induction of antioxidant enzymes including QR, GST, γ ‐glutamylcysteine synthase, glutathione reductase, and heme oxygenase 1 in hepa1c1c7 mouse hepatoma cells. The compound increased the luciferase activity of HepG2‐C8 cells, transfectants carrying antioxidant response element (ARE)‐luciferase gene, in a dose‐dependent manner, suggesting ARE‐mediated transcriptional activation of antioxidant enzymes. Alantolactone also stimulated the nuclear accumulation of Nrf2 that was inhibited by phosphatidylinositol 3‐kinase (PI3K) inhibitors. In conclusion, alantolactone appears to induce detoxifying enzymes via activation of PI3K and JNK signaling pathways, leading to translocation of Nrf2, and subsequent interaction between Nrf2 and ARE in the encoding genes. Copyright © 2008 John Wiley & Sons, Ltd.