Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. The purpose of the present study is to evaluate the effect of aspartame on angiogenesis in vivo chick chorioallantoic membrane (CAM) and wound-healing models as well as in vitro 2,3-bis-2 H-tetrazolium-5-carboxanilide (XTT) and tube formation assays. In CAM assay, aspartame increased angiogenesis in a concentration-dependent manner. Compared with the control group, aspartame has significantly increased vessel proliferation ( p < 0.001). In addition, in vivo rat model of skin wound-healing study showed that aspartame group had better healing than control group, and this was statistically significant at p < 0.05. There was a slight proliferative effect of aspartame on human umbilical vein endothelial cells on XTT assay in vitro, but it was not statistically significant; and there was no antiangiogenic effect of aspartame on tube formation assay in vitro. These results provide evidence that aspartame induces angiogenesis in vitro and in vivo; so regular use may have undesirable effect on susceptible cases.

Angiogenesis is needed for tumor growth and metastasis. For this reason, it represents an exciting target for cancer treatment. Some anti-angiogenic drugs may be useful to prevent angiogenesis during cancer treatment. The aim of this study is to investigate if Ankaferd (standardized herbal extract obtained from five different plants namely Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpina officinarum, and Urtica dioica) have an effect on angiogenesis in chick embryo chorioallontoic membrane. Ankaferd was applied at 1, 5, 20, 50% concentrations to the fertilized eggs on the 6th day. On the 7th and 8th days, all the fertilized eggs were opened and vessels were examined. No significant changes were observed in 1% Ankaferd group and control group. Significant inhibition in angiogenesis was observed in 5, 20, 50% Ankaferd groups. In chick embryo chorioallontoic membrane assay, the anti-angiogenic effect of Ankaferd was shown experimentally for the first time in the literature. The antiangiogenic affect of Ancafert was analyzed on vascular endothelial growth factors (VEGF-A,VEGF-C), and hypoxia-inducible factors (HIF1-A and HIF3-A) genes which have possible roles in angiogenesis on human mesenchimal stem cells and human umbilical vein endothelial cells. Ankaferd treatment increased VEGF-A gene expression levels in HUVECs. VEGF-A gene expression levels remained unchanced in hMSCs with %5 Ankaferd treatment. HIF1-A gene expression levels decreased in HUVECs, whereas increased in hMSCs with 5% Ankaferd treatment. The gene expression levels of HIF3-A increased both in HUVECs and hMSCs. In chick embryo chorioallontoic membrane assay, the anti-angiogenic effect of Ankaferd was shown experimentally for the first time in the literature. These findings may represents the potential uses of Ankaferd in cancer treatment as an anti-angiogenic agent. Due to gene expression analyses resuts in our study, Ankaferd affects the angiogenesis in anti-angiogenic procedure on VEGF and HIF genes.

We aimed to analyze the possible roles of FA and Zn on angiogenesis in vivo culture condition. CAM study revealed that FA and Zn decreased the vessel formation on CAM model. FGF1

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