Glabridin-induced vasorelaxation: Evidence for a role of BKCachannels and cyclic GMP.
OBJECTIVE
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.


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


RESULTS
Glabridin (30μM) relaxed arteries pre-constricted with the thromboxane A2analog U46619 (0.2μM) by ~60% in an endothelium-independent manner. Relaxation to 30μM glabridin was abolished by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (1μM) and by the BKCachannel blocker tetraethyammonium (1mM) but was unaffected by the estrogen receptor antagonist ICI182780. The concentration-response curve to glabridin (0.1 to 30μM) was downshifted by the KATPchannel blocker glibenclamide (10μM), the KVchannel blocker 4-aminopyridine (300μM), and the KIRblocker BaCl2(30μM). In U46619-contracted arteries partially relaxed by 0.1μM sodium nitroprusside, application of 10 and 30nM glabridin caused additional vasorelaxation. Glabridin (30μM) 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
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.
In-vivo Testing Facility, Molecular Bioprospection Department, Biotechnology Division CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, Uttar Pradesh, India.
Debrabata
D
Chanda
Division of Asthma, Allergy & Lung Biology, School of Medicine, King's College London, London WC2R 2LS, United Kingdom.
Jesus
J
Prieto-Lloret
In-vivo Testing Facility, Molecular Bioprospection Department, Biotechnology Division CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, Uttar Pradesh, India.
Arjun
A
Singh
In-vivo Testing Facility, Molecular Bioprospection Department, Biotechnology Division CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, Uttar Pradesh, India.
Hina
H
Iqbal
In-vivo Testing Facility, Molecular Bioprospection Department, Biotechnology Division CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, Uttar Pradesh, India.
Pankaj
P
Yadav
Division of Asthma, Allergy & Lung Biology, School of Medicine, King's College London, London WC2R 2LS, United Kingdom.
Vladimir
V
Snetkov
Division of Asthma, Allergy & Lung Biology, School of Medicine, King's College London, London WC2R 2LS, United Kingdom. Electronic address: Philip.aaronson@kcl.ac.uk.
Philip I
PI
Aaronson
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000502:physiology*; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D007529:Isoflavones; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D010636:Phenols; D000242:Cyclic AMP; C107601:glabridin
BK(Ca) channels; Cyclic GMP; Glabridin; Mesenteric artery; Rat
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