Isoflavones isolated from red clover (Trifolium pratense) inhibit smooth muscle contraction of the isolated rat prostate gland
Isoflavones isolated from red clover (Trifolium pratense) inhibit smooth muscle contraction of the isolated rat prostate gland
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DOI：
10.1016/j.phymed.2010.05.006
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发表时间：
2010-09-01
期刊：
影响因子：
7.9
通讯作者：
Ventura, S.
中科院分区：
文献类型：
--
作者：
Brandli, A.;Simpson, J. S.;Ventura, S.
本研究探讨红三叶是否含有影响大鼠前列腺平滑肌收缩的生物活性成分，以确定红三叶在治疗良性前列腺增生症中的药用价值是否得到药理作用的支持。对一种市售红三叶提取物进行了化学分级，从这些提取物中分离出不同的异黄酮类化合物(染料木素、芒柄花素和生物查宁A)，并在大鼠前列腺标本上观察了它们对前列腺收缩的影响。将分离出的部分与商业上可获得的异黄酮类(染料木素、芒柄花素和Bichanin A)的收缩效果进行了比较。用药理学手段研究其改善平滑肌收缩的作用机制。红三叶粗提物(Trinovin(R))可在一定频率范围内抑制电场刺激引起的大鼠前列腺收缩，IC50约为68微克/毫升，也可抑制外源性给予乙酰胆碱、去甲肾上腺素或三磷酸腺苷(ATP)引起的大鼠前列腺收缩。通过层析分离和高效液相色谱(HPLC)的最终纯化，可以分离出大豆苷元、毛蕊异黄素、芒柄花素、李子素、Pratensin、Bichanin A和染料木素。金雀异黄素、芒柄花素和生物粘附素A(100mM)均能抑制电场刺激引起的大鼠前列腺收缩。结论：红三叶中的异黄酮除具有抗增殖作用外，还具有抑制前列腺平滑肌收缩的作用。然而，观察这些平滑肌松弛效应所需的高浓度意味着，临床使用的剂量不太可能从这一机制中获得治疗益处。皇冠版权所有(C)2010，爱思唯尔有限公司出版。版权所有。
This study investigated whether red clover contains any bioactive constituents which may affect contractility of rat prostatic smooth muscle in an attempt to determine whether its medicinal use in the treatment of benign prostatic hyperplasia is supported by pharmacological effects. A commercially available red clover extract was chemically fractionated and various isoflavones (genistein, formononetin and biochanin A) were isolated from these fractions and their effects on contractility were examined on preparations of the isolated rat prostate gland. Contractile effects of the isolated fractions were compared with commercially available isoflavones (genistein, formononetin and biochanin A). Pharmacological tools were used to investigate the mechanism of action modifying smooth muscle contraction. Crude red clover extract (Trinovin (R)) inhibited electrical field stimulation induced contractions of the rat prostate across a range of frequencies with an IC50 of approximately 68 mu g/ml. Contractions of the rat prostate elicited by exogenous administration of acetylcholine, noradrenaline or adenosine 5'-triphosphate (ATP) were also inhibited. Chromatographic separation, and final purification by high performance liquid chromatography (HPLC) permitted the isolation of the isoflavones: daidzein, calycosin, formononetin, prunetin, pratensin, biochanin A and genistein. Genistein, formononetin and biochanin A (100 mu M) from either commercial sources or isolated from red clover extract inhibited electrical field stimulation induced contractions of the isolated rat prostate. It is concluded that isoflavones contained in red clover are able to inhibit prostatic smooth muscle contractions in addition to their antiproliferative effects. However, the high concentrations required to observe these smooth muscle relaxant effects mean that a therapeutic benefit from this mechanism is unlikely at doses used clinically. Crown Copyright (C) 2010 Published by Elsevier GmbH. All rights reserved.