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Glabridin-induced vasorelaxation: Evidence for a role of BKCa channels and cyclic GMP

Research output: Contribution to journalArticle

Debrabata Chanda, Jesus Prieto-Lloret, Arjun Singh, Hina Iqbal, Pankaj Yadav, Vladimir Snetkov, Philip I Aaronson

Original languageEnglish
Pages (from-to)26-34
JournalLife Sciences
Early online date26 Sep 2016
DOIs
Accepted/In press24 Sep 2016
E-pub ahead of print26 Sep 2016
Published15 Nov 2016

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Abstract

Background and purpose

Glabridin is a major flavonoid in Glycyrrhiza glabra (licorice) root, a traditional Asian medicine. Glabridin is reported to have anti-atherogenic, anti-inflammatory and anti-nephritic properties; however its effects on vascular tone remain unexplored.
Experimental approach

We examined the effect of glabridin on rat main mesenteric artery using isometric myography and also ELISA to measure cGMP levels.
Key results

Glabridin (30 μM) relaxed arteries pre-constricted with the thromboxane A2 analog U46619 (0.2 μM) by ~ 60% in an endothelium-independent manner. Relaxation to 30 μM glabridin was abolished by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (1 μM) and by the BKCa channel blocker tetraethyammonium (1 mM) but was unaffected by the estrogen receptor antagonist ICI182780. The concentration-response curve to glabridin (0.1 to 30 μM) was downshifted by the KATP channel blocker glibenclamide (10 μM), the KV channel blocker 4-minopyridine (300 μM), and the KIR blocker BaCl2 (30 μM). In U46619-contracted arteries partially relaxed by 0.1 μM sodium nitroprusside, application of 10 and 30 nM glabridin caused additional vasorelaxation. Glabridin (30 μM) approximately doubled tissue [cyclic GMP]. Application of the phosphodiesterase inhibitor isobutylmethylxanthine caused a much larger rise in [cyclic GMP], and glabridin failed to cause vasorelaxation or a further rise in [cGMP] when co-applied with IBMX.
Conclusions and implications

Vasorelaxation to glabridin is dependent on the opening of K+ channels, particularly BKCa, probably caused by a rise in cellular [cyclic GMP] owing to phosphodiesterase inhibition. In the presence of sodium nitroprusside an effect of glabridin is observed at nM concentrations, similar those measured in plasma following human ingestion of licorice flavonoid oil.

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