Hericium erinaceus Inhibits TNF-[alpha]-Induced Angiogenesis and ROS Generation through Suppression of MMP-9/NF-[kappa]B Signaling and Activation of Nrf2-Mediated Antioxidant Genes in Human EA.hy926 Endothelial Cells

• Published in: Oxidative medicine and cellular longevity 2016-01, Vol.2016
• Main Authors: Chang, Hebron C, Yang, Hsin-Ling, Pan, Jih-Hao, Korivi, Mallikarjuna, Pan, Jian-You, Hsieh, Meng-Chang, Chao, Pei-Min, Huang, Pei-Jane, Tsai, Ching-Tsan, Hseu, You-Cheng
• Format: Article
• Language: English
• Subjects: Angiogenesis; Antioxidants; Apoptosis; Binding sites; Biotechnology; Cardiovascular disease; Cell adhesion & migration; Cell growth; Chinese medicine; Diabetic retinopathy; Endothelium; Enzymes; Ethanol; Flavonoids; Fluorescence microscopy; Gene expression; Genes; Inflammatory diseases; Mushrooms; Nutrition; Phytochemicals; Polyphenols; Proteins; Studies; Tumor necrosis factor; Tumor necrosis factor-TNF
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2016/8257238

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 μg/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-κB (NF-κB) followed by suppression of I-κB (inhibitor-κB) 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-E2 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-κB and Nrf2-antioxidant signaling pathways.