Nanocurcumin Inhibits Angiogenesis via Down-regulating hif1a/VEGF-A Signaling in Zebrafish

Background: Curcumin has anti-inflammatory, antioxidant and anticancer properties. Despite the considerable evidence showing that curcumin is an efficacious and safe compound for multiple medicinal benefits, there are some demerits with respect to the therapeutic effectiveness of curcumin, namely, poor stability and solubility, and its role in angiogenesis in vivo is still not yet clear. More recently, the biodegradable polymer nanoparticles have been developed. This offers promise for the therapeutic effectiveness of curcumin by increasing its bioavailability, solubility and retention time. : Here, we compared the medicinal effectiveness of curcumin and nanocurcumin (NC), and found that nanocurcumin can inhibit angiogenesis more effectively than curcumin in zebrafish. Tests of proliferation and apoptosis showed no difference between nanocurcumin-treated and wildtype embryos. Results: qPCR and in situ hybridization experiments indicated that the VEGF signaling pathway genes, vegfa, VEGF-C and flt4 were all down-regulated after nanocurcumin treatment, and vegfa over-expression rescued the vascular defective phenotype. Moreover, hif1a expression also decreased and hif1a over-expression also rescued the vascular defective phenotype but the Notch signaling pathway had no difference after nanocurcumin treatment. Conclusion: These results indicate that nano curcumin inhibits angiogenesis in zebrafish by downregulating hif1a/vegfa signaling pathway. Hence, our work reveals the key role of nanocurcumin in angiogenesis in vivo.