Evidence for antiangiogenic potentials of Herniarin (7-methoxycoumarin) | Abstract
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Evidence for antiangiogenic potentials of Herniarin (7-methoxycoumarin)

Author(s): Narshimamurthy Anegundi and Katti Pancharatna

Coumarins are known for their diverse biological activities. In this study, antiangiogenic potentials of Herniarin (7-methoxy derivative of coumarin-7MC) were tested using embryonic angiogenesis of zebrafish (Danio rerio) as model. Laboratory raised developing embryos (in triplicate sets of 20 embryos/set) were exposed to 0, 1, 2, 3, 4, and 5mM concentrations of 7MC from 6hpf (hours post fertilization) until completion of embryogenesis. After hatching (72hpf) development trajectory of larva was traced for a week. At 72hpf, patterning of blood vessels, detection of blood flow by the presence of red blood cells (RBC) by globin expression, cardiac anomalies/heart rates, cellular apoptosis, morphological deformities and mortality rates were recorded. IC50 (50% ISV inhibitory concentration) and LC50 (50% lethal concentration) were determined for 7MC exposed larvae. Whole mount staining for alkaline phosphatase at 72 hpf indicated that formation of major blood vessels Viz. intersegmental vessels (ISV), dorsal aorta (DA), dorsal longitudinal anastomotic vessel (DLAV), posterior cardinal vein (PCV) and common cardinal veins (CCV) was perturbed and blood flow in them was disturbed in larvae of chemical exposed embryo sin comparison with corresponding controls. Exposure of embryos to higher concentrations (> 4mM 7MC) not only interfered blood vessel patterning but resulted in a decrease in heart rates, tail distortions, increased cellular apoptosis and elevated mortality rates. These results suggest that 7MC manifests antiangiogenic effects on zebrafish embryonic angiogenesis with IC50 value of 2.64mM. This biological property of 7MC may be explored in tumour suppressor therapeutics to enhance the antiangiogenic effects drugs in synergistic combination.