Nrf2‐mediated induction of detoxifying enzymes by alantolactone present in Inula helenium

Abstract

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, gamma-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.

Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C NMR spectral data and biological properties

“…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 (Seo et al, 2008). Grosheimin (264), isolated from the medicinal plants of Youngia japonica, exhibited strong antiallergic and antioxidant activities (Yae et al, 2009).…”

Isoalantolactone fromInula heleniumCaused Nrf2-Mediated Induction of Detoxifying Enzymes

“…3,4 Our previous study demonstrated that sesquiterpenes isolated from Inula helenium (also known as Elecampane) induced NQO1 (QR), an anticarcinogenic marker enzyme. 5,6 In an attempt to elucidate the underlying mechanism of phase 2 enzyme induction by the sesquiterpene isoalantolactone, the effect of isoalantolactone (Fig. 1) on Nrf2=ARE activation was investigated.…”

Protection by Chrysanthemum zawadskii extract from liver damage of mice caused by carbon tetrachloride is maybe mediated by modulation of QR activity

“…Further chromatographic fractionation to search for active component(s) resulted in active fraction (CZ-6) which contains (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro[4,5]de cane as QR inducer, belonging to acetylene family. Although the fraction showed relatively weak activity in QR induction compared to other known phytochemicals [8,13-16], its QR-inducing potential of the fraction at the 20 µg/mL was compatible with 10 µM tert-butylhydroquinone (tBHQ), a known QR inducer, in BPRc1 cells. Furthermore, its relatively low QR-inducing potential in BPRc1 cells with defective arylhydrocarbon receptor translocator (arnt) indicates that the fraction consists of a mixture of bifunctional inducer and monofunctional inducer.…”