title: Hericium erinaceus Inhibits 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.
abstract: 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.
authors.affiliation: Department of Biotechnology and Bioinformatics, Asia University, Taichung 41354, Taiwan.
authors.forename: Hebron C
authors.initials: HC
authors.lastname: Chang
authors.affiliation: Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Yang
authors.affiliation: Department of Biotechnology and Bioinformatics, Asia University, Taichung 41354, Taiwan.
authors.forename: Jih-Hao
authors.initials: JH
authors.lastname: Pan
authors.affiliation: Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
authors.forename: Mallikarjuna
authors.initials: M
authors.lastname: Korivi
authors.affiliation: Department of Biotechnology and Bioinformatics, Asia University, Taichung 41354, Taiwan.
authors.forename: Jian-You
authors.initials: JY
authors.lastname: Pan
authors.affiliation: Department of Biotechnology and Bioinformatics, Asia University, Taichung 41354, Taiwan.
authors.forename: Meng-Chang
authors.initials: MC
authors.lastname: Hsieh
authors.affiliation: Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
authors.forename: Pei-Min
authors.initials: PM
authors.lastname: Chao
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
authors.forename: Pei-Jane
authors.initials: PJ
authors.lastname: Huang
authors.affiliation: Institute of Public Health, China Medical University, Taichung 40402, Taiwan.
authors.forename: Ching-Tsan
authors.initials: CT
authors.lastname: Tsai
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan; Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
authors.forename: You-Cheng
authors.initials: YC
authors.lastname: Hseu
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000737:chemistry; D020533:Angiogenesis Inhibitors / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D000975:Antioxidants / Q000378:metabolism; D001487:Basidiomycota / Q000737:chemistry*; D042783:Endothelial Cells / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D005978:Glutathione
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