Inhibition of detrusor contractility by a flavonoid fraction of Bryophyllum pinnatum - a new option to treat the overactive bladder syndrome

Abstract

Patients with overactive bladder syndrome (OAB) suffer from urgency with/without incontinence, frequency, and nocturia. Antimuscarinic agents are used as a first-line therapy with clinical benefit, but anticholinergic side effects. Patients fail to respond adequately. Therefore, we recently investigated the inhibitory effect of Bryophyllum pinnatum leaf press juice on porcine detrusor contractility in vitro. To identify the active compounds in B. pinnatum, we tested the effects of a flavonoid and bufadienolide fraction on the contraction of the porcine bladder strips. In a previous profiling 9 different flavonoids have been isolated and identified from the MeOH extract of B. pinnatum leaves. For our experiments the MeOH extract of B. pinnatum was partitioned between CH2Cl2/H2O to separate flavonoids from lipophilic bufadienolides. The H2O-phase was separated on a Diaion HP-20 CC to receive a flavonoid fraction. Detrusor muscle strips used for the contractility experiments were prepared from porcine bladders. In an organ bath chamber, we investigated the effect of the purified flavonoid fraction as well as of oxybutynin on the contraction of the bladder strips. The contraction was induced by Electric Field Stimulation (EFS). Flavonoid fraction concentrations of 0.7, 0.8, and 1 mg/mL reduced the contraction of bladder strips stimulated by EFS to 92.3 ± 14.3%, 60.0 ± 10.0%, and 37.0 ± 8.8% after 74 min, respectively, of the contraction measured before treatment (100%). Concentrations < 0.7 mg/mL had no inhibitory effect, and concentrations > 1 mg/mL showed an irreversible alteration of the muscle contractility. Oxybutynin (10-7 M and 10-6 M) reduced the contraction to 27.9 ± 3.6% and 14.1 ± 3.3%, respectively. The flavonoid fraction of B. pinnatum inhibited the porcine detrusor contraction in a dose- and time-dependent manner. Further investigations are ongoing to study the possible synergistic inhibitory effect of the isolated bufadienolide fraction on the detrusor contractility.