title: Antrodia salmonea inhibits TNF-α-induced angiogenesis and atherogenesis in human endothelial cells through the down-regulation of NF-κB and up-regulation of Nrf2 signaling pathways.
abstract: BACKGROUND
  Antrodia salmonea (AS) is known as a traditional Chinese medicine, but very few biological activities have been reported.
  
  
  METHODS
  The present study was aimed to investigate the anti-angiogenic and anti-atherosclerotic potential of the fermented culture broth of AS against tumor necrosis factor-α (TNF-α)-stimulated human endothelial (EA.hy 926) cells.
  
  
  RESULTS
  The non-cytotoxic concentrations of AS significantly inhibited TNF-α-induced migration/invasion and capillary-like tube formation in EA.hy 926 cells. Furthermore, AS suppressed TNF-α-induced activity and expression of matrix metalloproteinase-9 (MMP-9), and cell-surface expression of intercellular adhesion molecule-1 (ICAM-1), which was associated with abridged adhesion of U937 leukocytes to endothelial cells. Moreover, AS significantly down-regulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor κB (NF-κB) followed by suppression of I-κB degradation and phosphorylation of I-κB kinase-α (IKKα). Notably, the protective effect of AS was directly correlated with the increased expression of hemeoxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCLC), which was reasoned by nuclear translocation and transactivation of NF-E2 related factor-2 (Nrf2)/antioxidant response element (ARE). Furthermore, HO-1 knockdown by HO-1-specific shRNA diminished the protective effects of AS on TNF-α-stimulated invasion, tube formation, and U937 adhesion in EA.hy 926 cells.
  
  
  CONCLUSIONS
  Taken together, these results suggest that Antrodia salmonea may be useful for the prevention of angiogenesis and atherosclerosis.
authors.affiliation: Institute of Nutrition, College of Health Care, China Medical University, Taichung 40402, Taiwan.
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Yang
authors.affiliation: Institute of Biotechnology and Bioinformatics, Asia University, Taichung 413, Taiwan.
authors.forename: Hebron C
authors.initials: HC
authors.lastname: Chang
authors.affiliation: Institute of Nutrition, College of Health Care, China Medical University, Taichung 40402, Taiwan.
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Lin
authors.affiliation: Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
authors.forename: K J
authors.initials: KJ
authors.lastname: Senthil Kumar
authors.affiliation: Institute of Nutrition, College of Health Care, China Medical University, Taichung 40402, Taiwan.
authors.forename: Chun-Huei
authors.initials: CH
authors.lastname: Liao
authors.affiliation: Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Department of Medical Research, Chi-Mei Medical Center, Tainan 710, Taiwan.
authors.forename: Kai-Yuan
authors.initials: KY
authors.lastname: Lin
authors.affiliation: Institute of Biotechnology and Bioinformatics, Asia University, Taichung 413, Taiwan; Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan. Electronic address: ychseu@mail.cmu.edu.tw.
authors.forename: You-Cheng
authors.initials: YC
authors.lastname: Hseu
mesh_terms: D055491:Antrodia / Q000737:chemistry*; D050197:Atherosclerosis / Q000188:drug therapy; D002448:Cell Adhesion; D002470:Cell Survival; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020298:U937 Cells; D015854:Up-Regulation
chemical_list: D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D020780:Matrix Metalloproteinase 9; D005721:Glutamate-Cysteine Ligase
keywords: ARE; AS; Antrodia salmonea; DMEM; Dulbecco's Modified Eagle's medium; EA.hy 926 cells; FBS; FITC; GSH; HO-1; Hemeoxygenase-1; I-κB; I-κB kinase-α; ICAM-1; IKKα; MMP-9; NF-κB; Nrf2; PBS; TNF-α; antioxidant response element; fetal bovine serum; fluorescein isothiocyanate; glutathione; inhibitor-κB; intercellular adhesion molecule-1; matrix metalloproteinase-9; nuclear factor erythroid 2-related factor 2; nuclear factor-κB; phosphate buffer saline; tumor necrosis factor-α; γ-GCLC; γ-glutamylcysteine synthetase