. 2019; 16(3): 303-309

Anti-Angiogenic activity of flunarizine by in ovo, in vitro and in vivo assays.

Chandana Kamili1, Ravi Shankar Kakaraparthy2, Uma Maheshwararao Vattikuti3
1Cmr College Of Pharmacy, Hyderabad- 501401 (telangana), India.
2Department Of Pharmacology, Sri Sai Aditya Institute Of Pharmaceutical Sciences And Research, Surampalem. (andra Pradesh),india.
3Department Of Pharmacognosy, Trr College Of Pharmacy, Hyderabad- 500079 (telangana), India.

INTRODUCTION: The involvement of T-type calcium channels in cell proliferation and the role of sodium channels in cell migration have been extensively studied in angiogenesis. In the present study Flunarizine, a dual sodium /calcium channel blocker; was selected to evaluate its anti-angiogenic potential. This can be therapeutically beneficial in the diseases caused due to pathologically excess angiogenesis.
METHODS: The anti-angiogenic activity of ion channel blocker was screened by chick chorioallantoic membrane assay (in ovo), Rat aortic ring assay, Endothelial Cell Proliferation Assay, Transwell Migration Assay, Matrigel Cord-Like Morphogenesis Assay (in vitro) and sponge impantation method (in vivo). The anti-angiogenic activity of the test drug was compared with the standard anti-angiogenic drug Bevacizumab and in addition, the test responses were compared with the angiogenic factor VEGF, at a maximal concentration of 500pM.
RESULTS: In the chorioallantoic membrane assay, number of branching points and angiogenic score were evaluated and significant results were observed at 10-5M and 10-4M. In the aortic ring assay reduction in the area of sprouts were observed with 5-10µM and a significant reduction in weight of sponges, number of blood vessels formed and hemoglobin content were observed at all the three tested concentrations of Flunarizine in the sponge implantation method. In the studies on Human umbilical vein endothelial cells the test drug (1-100 nM) showed significant inhibition of proliferation, migration and decrease in network length of cord like tubes in a dose dependent manner.
DISCUSSION AND CONCLUSION: Flunarizine has significant anti-angiogenic action by inhibiting the cell proliferation, migration and cord like tube formation, which have resulted by blocking the T-type calcium and sodium channels.

Keywords: Anti-angiogenesis, chick chorioallantoic membrane assay, rat aortic ring assay, sponge impantation method, HUVECs, Flunarizine


Chandana Kamili, Ravi Shankar Kakaraparthy, Uma Maheshwararao Vattikuti. Anti-Angiogenic activity of flunarizine by in ovo, in vitro and in vivo assays.. . 2019; 16(3): 303-309

Corresponding Author: Chandana Kamili, India


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