Department of Toxicology and Pharmacology, Maastricht University, Maastricht, The Netherlands.
Department of Toxicology and Pharmacology, Maastricht University, Maastricht, The Netherlands; Netherlands Food and Consumer Product Safety Authority (NVWA), Utrecht, The Netherlands.
Eur J Pharmacol. 2015 Jan 5;746:132-7. doi: 10.1016/j.ejphar.2014.11.006. Epub 2014 Nov 15.
The food supplement quercetin is used as self-medication for prostate disorders and is known to induce vasorelaxation. The drug tamsulosin is used in the treatment of benign prostatic hyperplasia. A major side effect of tamsulosin is orthostatic hypotension, mediated by vasorelaxation resulting from α1-adrenoceptor blockade. The overlapping profile prompted us to investigate the pharmacodynamic interaction of quercetin with tamsulosin. Since quercetin is extensively metabolized in the intestines and the liver, the metabolites quercetin-3-glucuronide and 4'O-methyl-quercetin were also examined. Vasorelaxation induced by the compounds was tested in rat mesenteric arteries (average diameter: 360±μm) constricted by the α1-adrenoceptor agonist phenylephrine. Tamsulosin (0.1nM) decreased phenylephrine sensitivity 17-fold (n=10). Quercetin (5, 10 and 20µM) also caused a decrease (2-, 4- and 6-fold respectively) of phenylephrine sensitivity, while 10µM of quercetin-3-glucuronide and 4'O-methyl-quercetin decreased this sensitivity (1.5- and 2-fold) only slightly (n=6). The combination of tamsulosin with quercetin or quercetin metabolites proved to be far more potent than the compounds in isolation. The combination of quercetin, quercetin-3-glucuronide or 4'O-methyl-quercetin with tamsulosin decreased the phenylephrine sensitivity approximately 200-, 35- and 150-fold (n=6). The strong pharmacodynamic interaction between the food supplement quercetin and tamsulosin underlines the potential of the impact of supplement-drug interactions that warrant more research.
膳食补充剂槲皮素被用作前列腺疾病的自我药疗，已知其可引起血管舒张。药物坦索罗辛用于治疗良性前列腺增生。坦索罗辛的一个主要副作用是体位性低血压，这是由α1-肾上腺素受体阻断引起的血管舒张介导的。由于两者的作用谱重叠，我们研究了槲皮素与坦索罗辛的药效学相互作用。由于槲皮素在肠道和肝脏中广泛代谢，因此还检查了其代谢物槲皮素-3-葡萄糖醛酸苷和 4'O-甲基槲皮素。在由α1-肾上腺素受体激动剂苯肾上腺素收缩的大鼠肠系膜动脉（平均直径：360±μm）中测试了化合物引起的血管舒张。坦索罗辛（0.1nM）使苯肾上腺素的敏感性降低了 17 倍（n=10）。槲皮素（5、10 和 20µM）也分别导致苯肾上腺素敏感性降低（分别为 2、4 和 6 倍），而 10µM 的槲皮素-3-葡萄糖醛酸苷和 4'O-甲基槲皮素仅略有降低（1.5-和 2 倍）（n=6）。坦索罗辛与槲皮素或槲皮素代谢物的组合比单独使用这些化合物的效果要强得多。槲皮素、槲皮素-3-葡萄糖醛酸苷或 4'O-甲基槲皮素与坦索罗辛的组合使苯肾上腺素的敏感性降低了约 200、35 和 150 倍（n=6）。膳食补充剂槲皮素与坦索罗辛之间的这种强烈的药效学相互作用强调了补充剂-药物相互作用的潜在影响，需要进行更多的研究。
