کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2535746 | 1559124 | 2008 | 8 صفحه PDF | دانلود رایگان |
In this study, we have investigated the actions of cryptotanshinone, an active, lipophilic component of the medicinal herb danshen (Salvia miltiorrhiza), on rat isolated coronary artery rings precontracted with 1 μM 5-hydroxytryptamine (5-HT) and its action compared to the ethanol-extractable fraction of the herb. Extraction of the ethanol-soluble fraction from danshen provided a yield of 1%. The amount of cryptotanshinone determined in this ethanol extract was 3.682%, and it was 6 times more potent than the extract in relaxing 5-HT-precontracted coronary artery rings; IC50 values were 2.65 ± 0.15 μg/ml and 15.82 ± 1.07 μg/ml, respectively. Involvement of endothelium-dependant mechanisms in their dilator effects were investigated by pretreatment of the artery rings with a cyclooxygenase inhibitor flurbiprofen (10 μM), a nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME, 100 μM), a muscarinic receptor antagonist atropine (100 nM), and by mechanical removal of the endothelium; none of these procedures produced a significant change on their dilator actions. Involvement of endothelium-independent mechanisms was investigated in endothelium-denuded artery rings pretreated with a β-adrenoceptor antagonist propranolol (100 nM), an adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ22536, 100 μM), a guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 μM), and a potassium channel inhibitor tetraethylammonium (TEA, 100 mM); these also produced no change on their dilator actions. The possible involvement of Ca2+ channels was investigated in artery rings incubated with Ca2+-free buffer and primed with 1 μM 5-HT for 5 min prior to adding CaCl2 to elicit contraction. The danshen ethanol extract (100 μg/ml) abolished the CaCl2-induced vasoconstriction, whereas, cryptotanshinone (30 μg/ml) produced 59% inhibition. These findings suggest their vasorelaxant effects are independent of pathways mediated by the endothelium, muscarinic receptors, β-adrenoceptors, adenylyl cyclase, and guanylyl cyclase, whereas, inhibition of Ca2+ influx in the vascular smooth muscle cells is important for their vasodilator actions. The high vasodilator potency and the quantity of salvianolic acid B contained in danshen ethanolic extract suggest it is an important constituent in this medicinal herb.
Journal: European Journal of Pharmacology - Volume 578, Issues 2–3, 14 January 2008, Pages 253–260