Pharmacological Effects of Berberine and Palmatine on the Prostatic and Urethral Smooth Muscle of the Rabbit

ABSTRACT

PURPOSE: One of the major medical treatments for benign prostatic hyperplasia is targeted toward reducing bladder outlet obstruction by alpha-adrenoceptor blockade to relax the smooth muscle tone of the prostate. Berberine and palmatine, an isoquinoline alkaloids, have varied pharmacological actions and have been extensively used in folk medicine. A previous large scale screening test revealed that berberine derivatives have antagonistic effects at the alpha1-adrenoceptors, although they are less potent than prazosin. The aim of this study is to investigate the effect of the berberine and palmatine on the contractility of the isolated prostate, urethral and vascular smooth muscle tissues of the rabbit. MATERIALS AND METHODS: Muscle strips of the prostate, urethra and renal artery were obtained from 10-week-old male New Zealand White rabbits. In vitro isometric contraction was measured using organ bath study. Cumulative concentrations of phenylephrine as an agonist were added to produce concentration-response relationships. Breberin (1-500 microM) and palmatine (1-500 microM) were added to the bath before the repeated phenylephrine-induced concentration-response curve was made. Responses of developed tension to phenylephrine were plotted as percentage of the maximal increase for each concentration-response curve in the prostate, urethra and renal artery strips. RESULTS: Phenylephrine produced concentration-dependent contractions on the rabbit prostatic and urethral preparations. Berberine and palmatine induced a dose-dependent rightward shift of the dose-response curve of phenylephrine-induced contraction of both prostate and urethra with a reduction of maximal response, indicating the interactions of the two agents with phenylephrine in noncompetitive antagonism. The rank order of potency of the inhibitory effect was palmatine > berberine in the urethral tissue, while there was no significant difference between the two agents in the prostatic tissue. In the renal artery strips, both berberine and palmatine did not significantly inhibited the maximal contractile response to phenylephrine (1-50 microM). Higher concentration of berberine (500 microM) and palmatine (100-500 microM) decreased maximal contractile response induced by phenylephrine (0-10 microM), while they paradoxically increased maximal contraction induced by higher concentrations of phenylephrine (50-100 microM). CONCLUSIONS: Our results indicated that berberine or palmatine inhibited phenylephrine-induced contractions in urethral and prostatic smooth muscles, with no significant inhibition in the renal artery smooth muscle at lower concentration ranges of berberine and palmatine. A deeper understanding of the action mechanisms of berberine and palmatine would widen our therapeutic options for voiding disorders.