Antrodia salmonea inhibits TNF-伪-induced angiogenesis and atherogenesis in human endothelial cells through the down-regulation of NF-魏B and up-regulation of Nrf2 signaling pathways

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• 作者：Hsin-Ling Yang ; Hebron C. Chang ; Shu-Wei Lin ; K.J. Senthil Kumar ; Chun-Huei Liao ; Hui-Min Wang ; Kai-Yuan Lin ; You-Cheng Hseu
• 关键词：ARE ; antioxidant response element ; AS ; Antrodia salmonea ; HO-1 ; Hemeoxygenase-1 ; ICAM-1 ; intercellular adhesion molecule-1 ; IKK伪 ; I-魏B kinase-伪 ; I-魏B ; inhibitor-魏B ; MMP-9 ; matrix metalloproteinase-9 ; NF-魏B ; nuclear factor-魏B ; Nrf2 ; nuclear factor erythroid 2-related factor 2 ; TNF-伪 ; tumor necrosis factor-伪 ; 纬-GCLC ; 纬-glutamylcysteine synthetase ; DMEM ; Dulbecco's Modified Eagle's medium ; FBS ; fetal bovine serum ; PBS ; phosphate buffer saline ; GSH ; glutathione ; FITC ; fluorescein isothioc
• 刊名：Journal of Ethnopharmacology
• 出版年：10 January, 2014
• 年：2014
• 卷：151
• 期：1
• 页码：394-406
• 全文大小：2827 K

文摘

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-伪 (TNF-伪)-stimulated human endothelial (EA.hy 926) cells.

Results

The non-cytotoxic concentrations of AS significantly inhibited TNF-伪-induced migration/invasion and capillary-like tube formation in EA.hy 926 cells. Furthermore, AS suppressed TNF-伪-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-伪-induced nuclear translocation and transcriptional activation of nuclear factor 魏B (NF-魏B) followed by suppression of I-魏B degradation and phosphorylation of I-魏B kinase-伪 (IKK伪). Notably, the protective effect of AS was directly correlated with the increased expression of hemeoxygenase-1 (HO-1) and 纬-glutamylcysteine synthetase (纬-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-伪-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.