Anti-angiogenic effects of rhubarb and its anthraquinone derivatives.
BACKGROUND
Rhubarb root (Dahuang) is often included as an ingredient in traditional Chinese compound prescriptions for the treatment of inflammatory diseases. This application may possibly be mediated through anti-angiogensis and thus would shed light on its potential value in cancer therapy.


OBJECTIVE
To elucidate the anti-angiogenic properties of rhubarb root, we tested the inhibitory effects of different fractions and a series of anthraquinone derivatives against vessel formation in zebrafish embryos.


METHODS
The 95% ethanol extract and four subsequent fractions (n-hexane, ethyl acetate, n-butanol and aqueous fractions) of rhubarb root and five anthraquinone derivatives were investigated on zebrafish model by quantitative endogenous alkaline phosphatase assay and staining assay.


RESULTS
Ethyl acetate fraction showed the strongest inhibition of vessel formation by 52%. Three anthraquinones (aloe-emodin, emodin and rhein) displayed potent anti-angiogenic activities.


CONCLUSIONS
The angiogenic properties of rhubarb root may partly account for its use in inflammatory diseases. The anthraquinones with acidic or polar, hydrophilic substitution at C-6 or C-3 positions played a substantial role in inhibiting angiogenesis. The value of the zebrafish angiogenic model is further supported.
He
Zhi-Heng
ZH
Food and Drug Authentication Laboratory, Department of Biology and Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, PR China.
He
Ming-Fang
MF
Ma
Shuang-Cheng
SC
But
Paul Pui-Hay
PP
D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D008516:Medicine, Chinese Traditional; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D012250:Rheum / Q000737:chemistry*; D013329:Structure-Activity Relationship; D015027:Zebrafish
D020533:Angiogenesis Inhibitors; D000880:Anthraquinones; D010936:Plant Extracts; D000469:Alkaline Phosphatase