Inhibitory effect of the antidepressant St. John's wort (Hypericum perforatum) on rat bladder contractility in vitro

Objectives. To evaluate the effect of St. John's wort (SJW), an effective and safe herbal antidepressant, on rat bladder contractility. Recent data have suggested a strong association between depression and urinary incontinence. Methods. Strips were cut from the bladder body and placed in organ baths containing Krebs solution. Contractions were induced by electrical field stimulation (EFS) and, in some experiments, by exogenous alpha,beta (alpha,beta)-methylene adenosine triphosphate. Results. St. John's wort was significantly more active in inhibiting the EFS-induced contractions than the alpha,beta-methylene adenosine triphosphate-induced contractions, suggesting both a presynaptic site of action and a direct inhibition of bladder smooth muscle. The inhibitory effect of SJW on EFS-incluced contractions was unaffected by methysergide, haloperidol, phentolamine plus propranolol (antagonists that block the action of the neurotransmitters 5-hydroxytriptamine, dopamine, and noradrenaline on their own receptors), the L-type calcium channel antagonist verapamil, capsazepine (which blocks the vanilloid receptor), or cannabinoid CB1 receptor antagonist SR141716A. However, the opioid receptor antagonist naloxone significantly reduced the inhibitory effect of SJW on EFS-induced contractions. Among the chemical constituents of SJW tested, hyperforin and, to a lesser extent, the flavonoid kaempferol showed inhibitory effects. Conclusions. The results of our study demonstrated that SJW inhibits excitatory transmission of the rat urinary bladder and also directly inhibits smooth muscle contractility. The inhibitory effect on excitatory transmission could involve, at least in part, opioid receptors. SJW may be evaluated for its possible use in treating urinary incontinence in depressed patients. (C) 2004 Elsevier Inc.