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

Oxid Med Cell Longev. 2016;2016:8257238. doi: 10.1155/2016/8257238. Epub 2015 Dec 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / chemistry
  • Angiogenesis Inhibitors / chemistry
  • Anti-Inflammatory Agents / chemistry
  • Antioxidants / metabolism
  • Basidiomycota / chemistry*
  • Endothelial Cells / metabolism*
  • Glutathione / metabolism
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Inflammation
  • Intercellular Adhesion Molecule-1 / metabolism
  • Matrix Metalloproteinase 9 / metabolism*
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism*
  • Neovascularization, Pathologic*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / pharmacology


  • Angiogenesis Inducing Agents
  • Angiogenesis Inhibitors
  • Anti-Inflammatory Agents
  • Antioxidants
  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Glutathione