Goepel M, Hecker U, Krege S, Rübben H, Michel M C
Department of Urology, University of Essen, Germany.
Prostate. 1999 Feb 15;38(3):208-15. doi: 10.1002/(sici)1097-0045(19990215)38:3<208::aid-pros5>3.0.co;2-4.
We wanted to test whether phytotherapeutic agents used in the treatment of lower urinary tract symptoms have alpha1-adrenoceptor antagonistic properties in vitro.
Preparations of beta-sitosterol and extracts of stinging nettle, medicinal pumpkin, and saw palmetto were obtained from several pharmaceutical companies. They were tested for their ability to inhibit [3H]tamsulosin binding to human prostatic alpha1-adrenoceptors and [3H]prazosin binding to cloned human alpha1A- and alpha1B-adrenoceptors. Inhibition of phenylephrine-stimulated [3H]inositol phosphate formation by cloned receptors was also investigated.
Up to the highest concentration which could be tested, preparations of beta-sitosterol, stinging nettle, and medicinal pumpkin were without consistent inhibitory effect in all assays. In contrast, all tested saw palmetto extracts inhibited radioligand binding to human alpha1-adrenoceptors and agonist-induced [3H]inositol phosphate formation. Saturation binding experiments in the presence of a single saw palmetto extract concentration indicated a noncompetitive antagonism. The relationship between active concentrations in vitro and recommended therapeutic doses for the saw palmetto extracts was slightly lower than that for several chemically defined alpha1-adrenoceptor antagonists.
Saw palmetto extracts have alpha1-adrenoceptor-inhibitory properties. If bioavailability and other pharmacokinetic properties of these ingredients are similar to those of the chemically defined alpha1-adrenoceptor antagonists, alpha1-adrenoceptor antagonism might be involved in the therapeutic effects of these extracts in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction.
我们想要测试用于治疗下尿路症状的植物治疗剂在体外是否具有α1 -肾上腺素能受体拮抗特性。
从几家制药公司获得了β -谷甾醇制剂以及荨麻、药用南瓜和锯叶棕提取物。测试它们抑制[3H]坦索罗辛与人前列腺α1 -肾上腺素能受体结合以及[3H]哌唑嗪与克隆的人α1A -和α1B -肾上腺素能受体结合的能力。还研究了它们对克隆受体刺激的苯肾上腺素诱导的[3H]肌醇磷酸形成的抑制作用。
在可测试的最高浓度下，β -谷甾醇、荨麻和药用南瓜制剂在所有测定中均无一致的抑制作用。相比之下，所有测试的锯叶棕提取物均抑制放射性配体与人α1 -肾上腺素能受体的结合以及激动剂诱导的[3H]肌醇磷酸形成。在单一锯叶棕提取物浓度存在下的饱和结合实验表明存在非竞争性拮抗作用。锯叶棕提取物的体外活性浓度与推荐治疗剂量之间的关系略低于几种化学定义的α1 -肾上腺素能受体拮抗剂。
锯叶棕提取物具有α1 -肾上腺素能受体抑制特性。如果这些成分的生物利用度和其他药代动力学特性与化学定义的α1 -肾上腺素能受体拮抗剂相似，α1 -肾上腺素能受体拮抗作用可能参与这些提取物对提示良性前列腺梗阻的下尿路症状患者的治疗效果。
