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

Ethnopharmacological relevance: Antrodia salmonea (AS) is known as a traditional Chinese medicine, but very few biological activities have been reported. Materials and 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-alpha (TNF-alpha)-stimulated human endothelial (EA.hy 926) cells. Results: The non-cytotoxic concentrations of AS significantly inhibited TNF-alpha-induced migration/invasion and capillary-like tube formation in EA.hy 926 cells. Furthermore, AS suppressed TNF-alpha-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-alpha-induced nuclear translocation and transcriptional activation of nuclear factor kappa B (NF-kappa B) followed by suppression of I-kappa B degradation and phosphorylation of I-kappa B kinase-alpha (IKK alpha). Notably, the protective effect of AS was directly correlated with the increased expression of hemeoxygenase-1 (HO-1) and gamma-glutamylcysteine synthetase (gamma-GCLC), which was reasoned by nuclear translocation and transactivation of NF-E-2 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-alpha-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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.