Ferulic acid augments angiogenesis via VEGF, PDGF and HIF-1α

被引:131
作者
Lin, Chiu-Mei [4 ,5 ,6 ]
Chiu, Jen-Hwey [6 ,7 ,8 ]
Wu, I-Hsing [9 ]
Wang, Bao-Wei [9 ]
Pan, Chun-Ming [9 ]
Chen, Yen-Hsu [1 ,2 ,3 ]
机构
[1] Kaohsiung Med Univ, Dept Internal Med, Div Infect Dis, Kaohsiung Med Univ Hosp, Kaohsiung, Taiwan
[2] Kaohsiung Med Univ, Sch Med, Grad Inst Med, Kaohsiung, Taiwan
[3] Kaohsiung Med Univ, Sch Med, Trop Med Res Ctr, Kaohsiung, Taiwan
[4] Shin Kong Wu Ho Su Mem Hosp, Dept Emergency Med, Taipei, Taiwan
[5] Taipei Med Univ, Coll Med, Taipei, Taiwan
[6] Natl Yang Ming Univ, Sch Med, Inst Tradit Med, Taipei 112, Taiwan
[7] Vet Gen Hosp, Dept Surg, Div Gen Surg, Taipei 11217, Taiwan
[8] Vet Gen Hosp, Res Ctr Tradit Chinese Med, Taipei, Taiwan
[9] Shin Kong Wu Ho Su Mem Hosp, Cent Lab, Taipei, Taiwan
关键词
Ferulic acid; Angiogenesis; VEGF; PDGF; HIF-1; alpha; ENDOTHELIAL-CELL PROLIFERATION; GROWTH-FACTOR; EXPRESSION; POLYPHENOLS; CANCER; CYTOKINES; RESPONSES; CULTURE;
D O I
10.1016/j.jnutbio.2009.04.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Therapeutic angiogenesis is critical to wound healing and ischemic diseases such as myocardial infarction and stroke. For development of therapeutic agents, a search for new angiogenic agents is the key. Ferulic acid, a phytochemical found in many fruits and vegetables, exhibits a broad range of therapeutic effects on human diseases, including diabetes and cancer. This study investigated the augmenting effect of ferulic acid on angiogenesis through functional modulation of endothelial cells. Through endothelial cell migration and tube formation assays, ferulic acid (10(-6)-10(-4) M) was found to induce significant angiogenesis in human umbilical vein endothelial cells (HUVECs) in vitro without cytotoxicity. With chorioallantoic membrane assay, ferulic acid (10(-6)-10(-5) M) was also found to promote neovascularization in vivo. Using Western blot analysis and quantitative real-time polymerase chain reaction, we found that ferulic acid increased vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) expression in HUVECs. Furthermore, the amounts of hypoxic-induced factor (HIF) 1 alpha mRNA and protein, the major regulator of VEGF and PDGF, also showed up-regulation by ferulic acid. Electrophoretic migration shift assay showed that the binding activity of HIF-1 alpha was also enhanced with ferulic acid treatment of HUVECs. Moreover, inhibitors of extracellular-signal-regulated kinase 1/2 and phosphoinositide-3 kinase (PI3K) abolished the binding activity of HIF-1 alpha and the subsequent activation of VEGF and PDGF production by ferulic acid. Thus, both mitogen-activated protein kinase and PI3K pathways were involved in the angiogenic effects of ferulic acid. Taken together, ferulic acid serves as an angiogenic agent to augment angiogenesis both in vitro and in vivo. This effect might be observed through the modulation of VEGF, PDGF and HIF-1 alpha. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:627 / 633
页数:7
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