Anti-angiogenic effects of rhubarb and its anthraquinone derivatives

Ethnopharmacological relevance: 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. Aim of tire study: 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. Materials and 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.