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Antihypertensive activity of diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate: A continuation study in L-NAME treated wistar rats. Eur J Pharmacol 2019 Sep 05;858:172482

Date

06/25/2019

Pubmed ID

31233749

DOI

10.1016/j.ejphar.2019.172482

Scopus ID

2-s2.0-85067594435 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

In the present study, we report that neolignan1 (Diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate) relaxes the superior mesenteric artery in a concentration dependent manner (pD2 value 5.392 ± 0.04; n = 8 for endothelium intact and 5.204 ± 0.03; n = 8 for endothelium denuded mesenteric rings, respectively). The relaxation response of neolignan1 was found to be endothelium independent and sensitive to 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-on (ODQ; 1 μM) and tetraethyl ammonium (TEA; 1 mM). In-silico studies showed good LibDock score (92.66) of neolignan1 with BKCa channel and are in well corroboration with ex-vivo study. Further, neolignan1 significantly decreased the systolic blood pressure, diastolic blood pressure and mean arterial pressure in the Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 50 mg/kg) treated Wistar rats at the dose of 30 and 100 mg/kg given once orally for 15 days. In addition, neolignan1 is well tolerated up to 100 mg/kg when given as a repeated dose, once orally for 28 days in Swiss albino mice. Neolignan1 was well absorbed from oral route, reached peak at 4 h and eliminated below detection level by 12 h after administration. Our present study concludes that neolignan1 produced relaxation in superior mesenteric artery by opening of BKCa channel and produced significant antihypertensive activity in L-NAME treated Wistar rats and was well tolerated by the experimental animal.

Author List

Singh A, Kumar BS, Iqbal H, Alam S, Yadav P, Verma AK, Khan F, Shanker K, Hanif K, Negi AS, Chanda D

Author

Hina Iqbal PhD Postdoctoral Researcher 2 in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antihypertensive Agents
Coumaric Acids
Female
Humans
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
Lignans
Male
Mesenteric Arteries
Mice
Molecular Docking Simulation
NG-Nitroarginine Methyl Ester
Protein Conformation
Rats
Rats, Wistar
Vasodilation