Isoflavones isolated from red clover (Trifolium pratense) inhibit smooth muscle contraction of the isolated rat prostate gland.
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) inhibited electrical field stimulation induced contractions of the rat prostate across a range of frequencies with an IC(50) of approximately 68 microg/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 microM) 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.
Brandli
A
A
Prostate Research Co-operative, Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Simpson
J S
JS
Ventura
S
S
D000109:Acetylcholine; D000255:Adenosine Triphosphate; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine; D010936:Plant Extracts / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D029921:Trifolium / Q000737:chemistry*
D007529:Isoflavones; D010936:Plant Extracts; D000255:Adenosine Triphosphate; D000109:Acetylcholine; D009638:Norepinephrine