The angiogenic effects of Angelica sinensis extract on HUVEC in vitro and zebrafish in vivo

• Published in: Journal of cellular biochemistry 2008-01, Vol.103 (1), p.195-211
• Main Authors: Lam, Hio-Wa, Lin, Hui-Chao, Lao, Sin-Cheng, Gao, Jian-Li, Hong, Si-Jia, Leong, Chi-Weng, Yue, Patrick Ying-Kit, Kwan, Yiu-Wa, Leung, Anskar Yu-Hung, Wang, Yi-Tao, Lee, Simon Ming-Yuen
• Format: Article
• Language: English
• Subjects: Angelica sinensis; Angelica sinensis - chemistry; angiogenesis; Animals; Cell Movement - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Expression Regulation - drug effects; Humans; HUVEC; MAP Kinase Signaling System - drug effects; Neovascularization, Physiologic - drug effects; p38 Mitogen-Activated Protein Kinases - metabolism; Phenotype; Plant Extracts - chemistry; Plant Extracts - pharmacology; RNA, Messenger - genetics; S Phase - drug effects; Umbilical Veins - blood supply; Umbilical Veins - cytology; Umbilical Veins - drug effects; Umbilical Veins - metabolism; VEGF; Zebrafish
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.21403

Angiogenesis plays an important role in a wide range of physiological processes such as wound healing and fetal development. Many diseases are associated with imbalances in regulation of angiogenesis, in which it is either excessive or there is insufficient blood vessel formation. Angelica sinensis (AS), commonly used in the prescriptions of Chinese medicine, is a potential candidate for curing such diseases. However, biological effects of AS on angiogenesis and underlying mechanisms are yet to be fully elucidated. This investigation describes the angiogenic effects of AS extract on human endothelial cells (HUVEC) in vitro and zebrafish in vivo. The extract was demonstrated, by XTT assay and microscopic cell counting, to stimulate the proliferation of HUVEC; in addition, flow cytometry analysis indicated that the extract increased the percentage of HUVEC in the S phase. The wound healing migration assay illustrated that a dramatic increase in migration could be measured in AS extract‐treated HUVEC. Meanwhile, the number of invaded cells and the mean tube length were significantly increased in AS extract treatment groups. The extract was also demonstrated to promote changes in subintestinal vessels (SIVs) in zebrafish, one feature of angiogenesis. In addition, AS extract was found by real‐time PCR to enhance vascular endothelial growth factor (VEGF) mRNA expression. In a bead‐based immunoassay, higher levels of p38 and JNK 1/2 expression were also observed in effusions compared with control cells. All results suggest that Angelica sinensis extract can promote angiogenesis, and that the angiogenic effects involve p38 and JNK 1/2 phosphorylation. J. Cell. Biochem. 103: 195–211, 2008. © 2007 Wiley‐Liss, Inc.