Anti-angiogenic effect and mechanism of rhein from Rhizoma Rhei.
OBJECTIVE
Rhein is a major bioactive component in rhubarb (Dahuang), a famous traditional Chinese medicine derived from the rhizome of Rheum palmatum and related species. It was reported to have antitumor and anti-inflammatory properties. Our previous studies found rhein displaying potent anti-angiogenic activities in a zebrafish embryo model. Its action mechanisms need further elucidation.


METHODS
The inhibition effect of vessel formation was checked by microscopic imaging on Tg(fli1a:EGFP)y1 zebrafish embryos. Then the action mechanism of rhein was investigated by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) on wild type zebrafish embryos and further tested on human umbilical vein endothelial cells.


RESULTS
At 20μM, rhein could almost completely block intersegmental blood vessels formation at both 48 and 72hpf, and completely inhibit subintestinal vessel plexus formation at 72hpf. Rhein affected multiple molecular targets related to angiogenesis, particularly angpt2 and tie2, and also inhibited endothelial cell migration.


CONCLUSIONS
Rhein could inhibit angiogenesis, which may play a role in antitumor and anti-inflammatory actions.
School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, P.R. China.
Zhi-Heng
ZH
He
Rui
R
Zhou
Ming-Fang
MF
He
Clara Bik-San
CB
Lau
Grace Gar-Lee
GG
Yue
Wei
W
Ge
Paul Pui-Hay
PP
But
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000378:metabolism; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects* / Q000254:growth & development; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D042783:Endothelial Cells; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D042787:Receptor, TIE-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012250:Rheum / Q000737:chemistry*; D027343:Rhizome; D014471:Umbilical Veins; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000880:Anthraquinones; D004365:Drugs, Chinese Herbal; D029961:Zebrafish Proteins; C504921:angptl2b protein, zebrafish; D042787:Receptor, TIE-2; C468146:tek protein, zebrafish; C020491:rhein