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

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• 作者：Debrabata Chanda^b ; Jesus Prieto-Lloret^a ; Arjun Singh^b ; Hina Iqbal^b ; Pankaj Yadav^b ; Vladimir Snetkov^a ; Philip I Aaronson^a ; ^{Philip.aaronson@kcl.ac.uk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BKCa channels ; Cyclic GMP ; Glabridin ; Mesenteric artery ; Rat
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：165
• 期：Complete
• 页码：26-34
• 全文大小：2952 K

文摘

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.

c_2">Experimental approach

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

c_3">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 BK_Ca 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 K_ATP channel blocker glibenclamide (10 μM), the K_V channel blocker 4-aminopyridine (300 μM), and the K_IR 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.

c_4">Conclusions and implications

Vasorelaxation to glabridin is dependent on the opening of K⁺ channels, particularly BK_Ca, 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.