Stimulatory effect of Cinnamomum cassia and cinnamic acid on angiogenesis through up-regulation of VEGF and Flk-1/KDR expression.
Complementary and alternative medicine, Cinnamomum cassia is one of the medicinal plants that have been used to improve various diseases caused by insufficient blood circulation. However, relatively little work has been carried out on the angiogenic responses of C. cassia and its active compound cinnamic acid (CA), despite its excellent pharmacological action. In this study, we study the effect of the ethanol extract of C. cassia (CCE) and its active compound CA, on angiogenic processes in in vitro and in vivo. In the Matrigel plug assay in vivo, CCE and CA dose dependently increased von Willebrand Factor (vWF) antigen expression, and hemoglobin contents, whose elevation paralleled the onset of angiogenesis and was considered an early indicator of endothelial activation. CCE and CA induced endothelial cells proliferation, migration and tubule-like structure in vitro. The 25-50% increase observed with CCE (at low doses of 1 or 10 ng/ml) in HUVEC and BAEC proliferation was similar to that observed with CA. The migration and tubule-like structure effect were observed with HUVEC and BAEC. However, the effect of CCE, CA and VEGF on cell proliferation, migration and tubule-like structure in HUVEC were bigger than the effect of CCE, CA and VEGF in BAEC. In addition, CCE and CA each induced 2.2-fold and 2.5-fold increases the production of VEGF, the mRNA expression of VEGF and Flk-1/KDR, the receptor involved in proliferation, migration, and tubule-like structure of endothelial cells. These data suggest that CCE and its active compound CA induce angiogenesis in vivo and in vitro, and this pathway is related with VEGF and Flk-1/KDR expression of endothelial cells.
Department of Acupuncture & Moxibustion, College of Oriental Medicine, KyungHee University, 1 Hoegidong, Dongdaemungu, Seoul 130-701, Republic of Korea.
Do-Young
DY
Choi
Yong-Hyeon
YH
Baek
Jeong-Eun
JE
Huh
Jeong-Min
JM
Ko
Hyunsu
H
Woo
Jae-Dong
JD
Lee
Dong-Suk
DS
Park
D000818:Animals; D001011:Aorta / Q000473:pathology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002934:Cinnamates / Q000008:administration & dosage / Q000494:pharmacology*; D032904:Cinnamomum aromaticum; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010936:Plant Extracts; D011247:Pregnancy; D014471:Umbilical Veins / Q000473:pathology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014841:von Willebrand Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D002934:Cinnamates; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; C029010:cinnamic acid; D040301:Vascular Endothelial Growth Factor Receptor-2