The angiogenic effects of Angelica sinensis extract on HUVEC in vitro and zebrafish in vivo.
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.
Lam
Hio-Wa
HW
Institute of Chinese Medical Sciences, University of Macau, Av. Padre Tomás Pereira S.J., Taipa, Macao, China.
Lin
Hui-Chao
HC
Lao
Sin-Cheng
SC
Gao
Jian-Li
JL
Hong
Si-Jia
SJ
Leong
Chi-Weng
CW
Yue
Patrick Ying-Kit
PY
Kwan
Yiu-Wa
YW
Leung
Anskar Yu-Hung
AY
Wang
Yi-Tao
YT
Lee
Simon Ming-Yuen
SM
D029971:Angelica sinensis / Q000737:chemistry*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010641:Phenotype; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D016196:S Phase / Q000187:drug effects; D014471:Umbilical Veins / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015027:Zebrafish; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D010936:Plant Extracts; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases