We evaluated the protective effects of crocetin against angiogenesis induced by vascular endothelial growth
factor (VEGF). Crocetin, the aglycone of crocin carotenoids, is found in saffron crocus (Crocus sativus L.) and gardenia
fruit (Gardenia jasminoides Ellis). The effects of crocetin on VEGF-induced angiogenesis were examined by in vitro tube
formation assays and following 14-day co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts.
The anti-angiogenic mechanism of crocetin was evaluated by examining its effects on VEGF-induced proliferation and
migration of human retinal microvascular endothelial cells (HRMECs) and phosphorylation of p38. Vascular endothelial
(VE)-cadherin, zonula occludens (ZO-1) and occludin, which are adherens and tight junction proteins, respectively, play a
major role in the control of vascular permeability. Therefore, we tested effects of crocetin on adhesion molecule
dissociation induced by VEGF. Crocetin significantly suppressed VEGF-induced tube formation by HUVECs and
migration of HRMECs. It also significantly inhibited phosphorylation of p38 and protected VE-cadherin expression.
These findings indicate that crocetin suppresses the VEGF-induced angiogenesis by inhibiting migration and that the
inhibition of phosphorylated-p38 and protection of VE-cadherin expression may be involved in its underlying mechanism
Keywords: Angiogenesis, carotenoid, crocetin, HRMEC, p38, VE-cadherin, vascular endothelial growth factor, saffron crocus, umbilical vein, endothelial cells, Crocetin, fibroblasts, permeability, atherosclerosis, abnormal angiogenesis, ophthalmologic field
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