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.

Journal: Oxidative medicine and cellular longevity
PMID: 26823953

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

  • Hebron C Chang
    Department of Biotechnology and Bioinformatics, Asia University, Taichung 41354, Taiwan.
  • Hsin-Ling Yang
    Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
  • Jih-Hao Pan
    Department of Biotechnology and Bioinformatics, Asia University, Taichung 41354, Taiwan.
  • Mallikarjuna Korivi
    Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
  • Jian-You Pan
    Department of Biotechnology and Bioinformatics, Asia University, Taichung 41354, Taiwan.
  • Meng-Chang Hsieh
    Department of Biotechnology and Bioinformatics, Asia University, Taichung 41354, Taiwan.
  • Pei-Min Chao
    Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
  • Pei-Jane Huang
    Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
  • Ching-Tsan Tsai
    Institute of Public Health, China Medical University, Taichung 40402, Taiwan.
  • You-Cheng Hseu
    Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.

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