Trans-resveratrol inhibits early blood vessel formation (vasculogenesis) without impairment of embryonic growth.
Resveratrol is a stilbene compound found in grapes and other sources. In this study we examined the effects of trans-resveratrol (4.38 - 438 microM/implant) in the vasculogenesis of yolk-sac membranes and its capacity to improve chick embryo growth. High concentrations of the stilbene (43.8 - 438 microM) significantly inhibited early vessel formation, decreasing the percentage vitelline vessels of 3.5-day embryos by 50% compared to the control. In addition, basic fibroblast growth factor-stimulated vasculogenesis (140% of vessels as compared to control) was partially reversed by t-resveratrol (35% of inhibition) and treatments with cyclooxygenase inhibitors (acetylsalicylic acid and indomethacin) as well a protein-kinase C (PKC) activator (phorbol-12,13-dibutyrate) decreased the vessel number to 60%, 50%, and 44%, respectively. Treatments with t-resveratrol (4.38 - 43.8 microM/implant) significantly increased the body length of embryos incubated in vitro uncoupled from any impairment in the body shape or detectable embryotoxic effect. We suggest that the antivasculogenic activity and the enhancement in embryonic growth promoted by non acute treatments with t-resveratrol were, at least in part, due to PKC inhibition. We suggest that t-resveratrol can be usable not only as a reliable functional nutriment, but also is useful for the development of prophylactic and/or therapeutic agents for treatment of angiogenic-degenerative diseases.
Laboratory of Medicinal Plants Pharmacology, Department of Pharmacology, Biological Sciences Center (CCB), Federal University of Santa Catarina (UFSC), University Campus, Trindade, Florianópolis, SC, Brazil. paulus@mbox1.ufsc.br
Paulo Fernando
PF
Dias
Fernanda Vieira
FV
Berti
Jarbas Mota
JM
Siqueira
Marcelo
M
Maraschin
Antônio Ricardo
AR
Gagliardi
Rosa Maria
RM
Ribeiro-do-Valle
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002642:Chick Embryo; D047108:Embryonic Development / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D013267:Stilbenes; D016222:Fibroblast Growth Factor 2; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D000077185:Resveratrol