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Hericium erinaceus  (HE) is an edible mushroom that has been shown to exhibit anticancer and anti-inflammatory activities. We investigated the antiangiogenic and antioxidant potentials of ethanol extracts of HE in human endothelial (EA.hy926) cells upon tumor necrosis factor- α - (TNF- α -) stimulation (10 ng/mL). The underlying molecular mechanisms behind the pharmacological efficacies were elucidated. We found that noncytotoxic concentrations of HE (50–200  μ g/mL) significantly inhibited TNF- α -induced migration/invasion and capillary-like tube formation of endothelial cells. HE treatment suppressed TNF- α -induced activity and/or overexpression of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). Furthermore, HE downregulated TNF- α -induced nuclear translocation and transcriptional activation of nuclear factor- κ B (NF- κ B) followed by suppression of I- κ B (inhibitor- κ B) degradation. Data from fluorescence microscopy illustrated that increased intracellular ROS production upon TNF- α -stimulation was remarkably inhibited by HE pretreatment in a dose-dependent manner. Notably, HE triggered antioxidant gene expressions of heme oxygenase-1 (HO-1),  γ -glutamylcysteine synthetase ( γ -GCLC), and glutathione levels, which may contribute to inhibition of ROS. Increased antioxidant status was associated with upregulated nuclear translocation and transcriptional activation of NF-E 2  related factor-2 (Nrf2) in HE treated cells. Our findings conclude that antiangiogenic and anti-inflammatory activities of  H. erinaceus  may contribute to its anticancer property through modulation of MMP-9/NF- κ B and Nrf2-antioxidant signaling pathways.

oxidative medicine and cellular longevity

Hericium erinaceusInhibits TNF-α-Induced Angiogenesis and ROS Generation through Suppression of MMP-9/NF-κB Signaling and Activation of Nrf2-Mediated Antioxidant Genes in Human EA.hy926 Endothelial Cells