Extract of the mushroom Mycoleptodonoides aitchisonii induces a series of anti-oxidative and phase II detoxifying enzymes through activation of the transcription factor Nrf2

Activation of the transcriptional factor Nrf2 is a powerful strategy for protecting oxidative stress-related disease. To find novel compounds from mushrooms, the NAD(P)H:quinone oxidoreductase 1 (NQO1)-inducing activity of 43 ethyl-acetate extracts of mushrooms were examined using Hepa1c1c7 cells. In this screening, an extract of Mycoleptodonoides aitchisonii significantly induced NQO1. This extract also increased ARE reporter activity and inhibited H ₂O₂-induced cell death in RAW264.7 cells. The induction of anti-oxidative and phase II enzymes was attenuated in peritoneal macrophages from Nrf2-deficient mice, so these activities were probably mediated by Nrf2 activation. Oral administration of the extract upregulated expression of these genes in the liver and small intestinal epithelium of mice. We purified 11 active compounds (including three novel ones), and dihydro-4-phenyl-2(3H)- furanone was the most effective NQO1-inducer. These results suggest that dietary intake of M. aitchisonii may contribute to the prevention of oxidative stress-related diseases by inducing anti-oxidative and phase II enzymes.