Testai Lara, Chericoni Silvio, Martelli Alma, Flamini Guido, Breschi Maria Cristina, Calderone Vincenzo
Department of Pharmacy, University of Pisa, Pisa, Italy.
Interdipartimental Center of Nutraceutical Research and Food for Healthy "Nutrafood", Università di Pisa, Pisa, Italy.
J Pharm Pharmacol. 2016 Sep;68(9):1177-83. doi: 10.1111/jphp.12585. Epub 2016 Jun 23.
Carvacrol, a monoterpene widely present in nature, is commonly used in the food industry and in cosmetics, besides to possess a plethora of pharmacological properties, among these also in vitro vasorelaxing effects and in vivo hypotensive responses. Although in rat aortic rings carvacrol evoked a vasodilatation both in the presence and in the absence of endothelium, in preparations with intact endothelial layer its vasoactive response markedly improved.
This study aimed at investigating the mechanism of action responsible for the endothelial component of the carvacrol-induced vasorelaxing response observed in rat isolated aortic rings.
Pharmacological characterization led us to exclude the involvement of NO pathway (neither L-NAME, NO biosynthesis inhibitor, nor ODQ, guanylate cyclase inhibitor, was able to modify the vascular effects of carvacrol) and of arachidonic acid cascade (no inhibitor intercepting the cascade influenced the endothelial-dependent vasodilatation of the monoterpene). Moreover, endothelial TRP channels were also not involved, as capsazepine did not antagonize vasorelaxing effect. Finally, endothelial potassium channels were considered as possible targets of carvacrol; indeed, two voltage-operated potassium (Kv) channel blockers, 4-aminopyridine and quinine, significantly reduced carvacrol potency and efficacy indices.
Kv channels seem to be responsible for vascular effects of the monoterpene typical of Labiatae family.
香芹酚是一种广泛存在于自然界的单萜类化合物，除了具有多种药理特性外，常用于食品工业和化妆品中，其中还包括体外血管舒张作用和体内降压反应。尽管在大鼠主动脉环中，无论有无内皮细胞，香芹酚均可引起血管舒张，但在具有完整内皮细胞层的制剂中，其血管活性反应明显增强。
本研究旨在探讨大鼠离体主动脉环中香芹酚诱导的血管舒张反应的内皮成分的作用机制。
药理学特性研究使我们排除了NO途径（L-NAME，NO生物合成抑制剂，以及ODQ，鸟苷酸环化酶抑制剂，均不能改变香芹酚的血管效应）和花生四烯酸级联反应（没有拦截该级联反应的抑制剂影响单萜类化合物的内皮依赖性血管舒张）的参与。此外，内皮瞬时受体电位通道也未参与其中，因为辣椒素不能拮抗血管舒张作用。最后，内皮钾通道被认为是香芹酚的可能靶点；实际上，两种电压门控钾（Kv）通道阻滞剂，4-氨基吡啶和奎宁，显著降低了香芹酚的效力和效能指数。
Kv通道似乎是唇形科典型单萜类化合物血管效应的原因。
