Bryophyllum pinnatum enhances the inhibitory effect of atosiban and nifedipine on human myometrial contractility: an in vitro study.

BACKGROUND: The herbal medicine Bryophyllum pinnatum has been used as a tocolytic agent in anthroposophic medicine and, recently, in conventional settings alone or as an add-on medication with tocolytic agents such as atosiban or nifedipine. We wanted to compare the inhibitory effect of atosiban and nifedipine on human myometrial contractility in vitro in the absence and in the presence of B. pinnatum press juice (BPJ). METHODS: Myometrium biopsies were collected during elective Caesarean sections. Myometrial strips were placed under tension into an organ bath and allowed to contract spontaneously. Test substances alone and at concentrations known to moderately affect contractility in this setup, or in combination, were added to the organ bath, and contractility was recorded throughout the experiments. Changes in the strength (measured as area under the curve (AUC) and amplitude) and frequency of contractions after the addition of all test substances were determined. Cell viability assays were performed with the human myometrium hTERT-C3 and PHM1-41 cell lines. RESULTS: BPJ (2.5 µg/mL), atosiban (0.27 µg/mL), and nifedipine (3 ng/mL), moderately reduced the strength of spontaneous myometrium contractions. When BPJ was added together with atosiban or nifedipine, inhibition of contraction strength was significantly higher than with the tocolytics alone (p = 0.03 and p < 0.001, respectively). In the case of AUC, BPJ plus atosiban promoted a decrease to 48.8 ± 6.3% of initial, whereas BPJ and atosiban alone lowered it to 70.9 ± 4.7% and to 80.9 ± 4.1% of initial, respectively. Also in the case of AUC, BPJ plus nifedipine promoted a decrease to 39.9 ± 4.6% of initial, at the same time that BPJ and nifedipine alone lowered it to 78.9 ± 3.8% and 71.0 ± 3.4% of initial. Amplitude data supported those AUC data. The inhibitory effects of BPJ plus atosiban and of BPJ plus nifedipine on contractions strength were concentration-dependent. None of the test substances, alone or in combination, decreased myometrial cell viability. CONCLUSIONS: BPJ enhances the inhibitory effect of atosiban and nifedipine on the strength of myometrial contractions, without affecting myometrium tissue or cell viability. The combination treatment of BPJ with atosiban or nifedipine has therapeutic potential.

Inhibition of porcine detrusor contractility by the flavonoid fraction of Bryophyllum pinnatum--a potential phytotherapeutic drug for the treatment of the overactive bladder syndrome.

AIMS: To determine if the phytotherapeutic agent, Bryophyllum pinnatum, could serve as an alternative drug for the overactive bladder syndrome, and to characterise the fraction responsible for the inhibition of detrusor contractility. METHODS: Fractions were prepared from the MeOH extract of B. pinnatum and further analysed by HPLC-PDA-MS. Detrusor muscle strips were prepared from porcine bladders and the electrically induced muscle contractility measured by organ bath. The effect of B. pinnatum leaf press juice (2.5-10%), a flavonoid fraction (0.1-1 mg/ml), and a bufadienolide fraction (0.1-40 µg/ml) on detrusor contractility was assessed and compared with controls (polar fraction (0.5-5 mg/ml) and oxybutynin (10(-8)-10(-6) M)). RESULTS: The press juice, at a concentration of 10% led to a reduction of detrusor contractility. Bladder strips treated with the flavonoid fraction showed a significant reduction of the contractility to 21.3 ± 5.2% (1 mg/ml) while the bufadienolide fraction had no inhibitory effect in the investigated concentrations. The polar fraction showed a reduction of the contractility in a pH-dependent fashion. At 10(-6) M concentration oxybutynin reduced the detrusor contractility to 21.9 ± 4.7%. CONCLUSIONS: The flavonoid fraction of Bryophyllum pinnatum reduces the porcine detrusor contractility in a dose- and time-dependent manner. Fractions from B. pinnatum may be a new pharmacological approach for the treatment of OAB.

Sleep quality in pregnancy during treatment with Bryophyllum pinnatum: an observational study.

INTRODUCTION: Poor sleep quality in pregnancy is frequent. A treatment with sedatives is problematic due to possible adverse effects for mother and embryo/foetus. In the present study, we investigated the sedative effect of Bryophyllum pinnatum, a phytotherapeutic medication used in anthroposophic medicine. In previous clinical studies on its tocolytic effect, B. pinnatum showed a good risk/benefit ratio for mother and child. A recent analysis of the prescribing pattern for B. pinnatum in a network of anthroposophic physicians revealed sleep disorders as one of the most frequent diagnoses for which these preparations are prescribed. MATERIALS AND METHODS: In this prospective, multi-centre, observational study, pregnant women suffering from sleep problems were treated with B. pinnatum (350mg tablets, 50% leaf press juice, Weleda AG, Arlesheim, dosage at physician's consideration). Sleep quality, daily sleepiness and fatigue were assessed with the aid of standardised questionnaires, at the beginning of the treatment and after 2 weeks. Possible adverse drug reactions perceived by the patients during the treatment were recorded. RESULTS: The number of wake-ups, as well as the subjective quality of sleep was significantly improved at the end of the treatment with B. pinnatum. The Epworth Sleeping Scale decreased, indicating a decrease of the tiredness during the day. There was, however, no evidence for prolongation of the sleep duration, reduction in the time to fall asleep, as well as change in the Fatigue Severity Scale after B. pinnatum. No serious adverse drug reactions were detected. CONCLUSION: B. pinnatum is a suitable treatment of sleep problems in pregnancy. The data of this study encourage further clinical investigations on the use of B. pinnatum in sleep disorders.

Bryophyllum pinnatum inhibits detrusor contractility in porcine bladder strips--a pharmacological study towards a new treatment option of overactive bladder.

AIMS: A broad spectrum of synthetic agents is available for the treatment of overactive bladder. Anti-cholinergic drugs show a poor compliance due to side effects. There is an increasing use of plant extracts in medicine. We have therefore investigated the inhibitory effects of leaf press juice from Bryophyllum pinnatum (Lam.) Oken (Kalanchoe pinnata L.) on bladder strips and compared the effects to that of oxybutynin. METHODS: Strips of porcine detrusor were prepared in Krebs solution and contractility was measured in a myograph system chamber aired with O2/CO2 at 37 °C. To induce contractions, electrical field stimulation (32 Hz, 40 V) was used for the inhibitory effect measurements, and carbachol (50 µM) for the relaxant effect measurements. Recordings were obtained in the absence and presence of increasing concentrations of Bryophyllum pinnatum leaf press juice (BPJ, 0.1-10%), and oxybutynin (10⁻7-10⁻³ M) as a reference substance. RESULTS: In inhibition experiments, BPJ as well as oxybutynin inhibited electrically induced contractions of porcine detrusor. BPJ at concentrations of 5% inhibited the contraction compared to a time matched control significantly by 74.6±10.2% (p<0.001). BPJ as well as oxybutynin relaxed carbachol pre-contracted porcine detrusor strips. The maximum relaxant effect of BPJ compared to a time matched control was 18.7±3.7 (p<0.05) at a concentration of 10% BPJ. CONCLUSIONS: Our investigations show that BPJ inhibits contractions induced by electrical field stimulation and relaxes carbachol-induced contractions. However, the effect was lower than that of the reference substance oxybutynin. It is important to continue in vitro experiments as well as clinical studies with BPJ that might offer a new treatment option for patients with OAB.

Leaf press juice from Bryophyllum pinnatum (Lamarck) Oken induces myometrial relaxation.

AIMS: The use of preparations from Bryophyllum pinnatum (Lamarck) Oken (Kalanchoe pinnata (Lamarck) Persoon) in tocolysis is supported by clinical evidence. We studied here the effect of B. pinnatum leaf press juice and its chemical fractions on the response of human myometrial strips. No data are available if the influence on myometrial strips of the juice differs from that of its components in the chemical fractions, in order to increase the pharmacological effect. METHODOLOGY: In vitro study to test the effect of repeated addition of B. pinnatum leaf press juice (BPJ) and its chemical components in several dilutions (undiluted, 1-10%) on myometrium strips hang up in a myograph chamber. Chemical analysis is including HPLC, MPLC with Sephadex LH-20 and TLC. RESULTS: All test solutions are inhibiting contractility by reducing the amplitude and the area under the curve (AUC) of the contractions. Undiluted BPJ and its undiluted chemical fraction 4 are reducing most effective these two parameters: the amplitude was at 78% of the baseline (95% CI (77-89); p<0.05) at the second addition of the BPJ and at 70% (95% CI (50-90); p<0.05) of the first addition of fraction 4; the AUC was at 82% (95% CI (69-95); p<0.05) of the baseline at the first addition of the press juice and at 51% (95% CI (27-74); p<0.05) at the first addition of fraction 4. The BPJ decreased amplitude and AUC significantly faster and increased frequency significantly faster than the control. Fractions could be tentatively assigned to bufadienolids, flavonoids and cinnamic acids. Fraction 4, accounted for flavonoids, increased the frequency of the contractions most effectively: 557% of the baseline (95% CI (316-797); p<0.05) at the first addition. CONCLUSION: Leaf juice of B. pinnatum and its flavonoid fraction are most effective in relaxing myometrial strips by inducing frequency.

Juice of Bryophyllum pinnatum (Lam.) inhibits oxytocin-induced increase of the intracellular calcium concentration in human myometrial cells.

The use of preparations from Bryophyllum pinnatum in tocolysis is supported by both clinical (retrospective comparative studies) and experimental (using uterus strips) evidence. We studied here the effect of B. pinnatum juice on the response of cultured human myometrial cells to stimulation by oxytocin, a hormone known to be involved in the control of uterine contractions by increasing the intracellular free calcium concentration ([Ca2+]i). In this work, [Ca2+]i was measured online during stimulation of human myometrial cells (hTERT-C3 and M11) with oxytocin, which had been pre-incubated in the absence or in the presence of B. pinnatum juice. Since no functional voltage-gated Ca2+ channels could be detected in these myometrial cells, the effect of B. pinnatum juice was as well studied in SH-SY5Y neuroblastoma cells, which are known to have such channels and can be depolarised with KCl. B. pinnatum juice prevented the oxytocin-induced increase in [Ca2+]i in hTERT-C3 human myometrial cells in a dose-dependent manner, achieving a ca. 80% inhibition at a 2% concentration. Comparable results were obtained with M11 human primary myometrial cells. In hTERT-C3 cells, prevention of the oxytocin-induced increase in [Ca2+]i was independent of the extracellular Ca2+ concentration and of voltage-dependent Ca2+-channels. B. pinnatum juice delayed, but did not prevent the depolarization-induced increase in [Ca2+]i in SH-SY5Y cells. Taken together, the data suggest a specific and concentration-dependent effect of B. pinnatum juice on the oxytocin signalling pathway, which seems to corroborate its use in tocolysis. Such a specific mechanism would explain the rare and minor side-effects in tocolysis with B. pinnatum as well as its high therapeutic index.

Nifedipine concentration in maternal and umbilical cord blood after nifedipine gastrointestinal therapeutic system for tocolysis.

OBJECTIVE: To determine nifedipine concentrations in maternal plasma at steady state, and maternal and umbilical cord plasma at delivery, after tocolysis with nifedipine gastrointestinal therapeutic system (GITS) tablets. DESIGN: Prospective clinical pharmacokinetic study. SETTING: Department of Obstetrics at the Zurich University Hospital. POPULATION: Pregnant women treated for threatened preterm labour. METHODS: GITS dosage titrated to clinical response (30-150 mg/day). Nifedipine concentrations by high-performance liquid chromatography and turbo ion spray tandem mass spectrometry. MAIN OUTCOME MEASURES: Steady-state nifedipine concentrations in maternal blood and nifedipine concentrations in maternal and corresponding umbilical cord blood at delivery. RESULTS: Steady-state nifedipine concentrations (micrograms/l, mean +/- SE) were 54 +/- 6 (all doses, n = 31), 38 +/- 8 (60 mg/day, n = 13), and 92 +/- 12 (150 mg/day, n = 7) (P < 0.002). Umbilical cord and maternal concentrations both declined in a ln-linear regression with elimination half-lives of 20.4 and 17.4 hours. Linear regression showed a correlation between umbilical and maternal concentrations of 0.77 +/- 0.1 (n = 21, mean +/- SE). CONCLUSIONS: Steady-state plasma nifedipine concentrations after repeated dosing with nifedipine GITS 30-150 mg/day in pregnant women with preterm labour do not exceed 100 micrograms/l; fetal levels are 77% of maternal levels.

[Natural remedies during pregnancy and lactation]. / Naturheilmittel während Schwangerschaft und Stillzeit.

Up to date there is a lack of systematically gathered data on the use of natural remedies (phytotherapeutic, homeopathic, anthroposophic, spagyric, Bach and Schussler remedies) during pregnancy and lactation. The aim of this non-representative pilot study on 139 women, who came for delivery to three institutions between mid-1997 and the beginning of 1998, was to receive data about how often and within which spectrum natural remedies are used during pregnancy and lactation. During pregnancy 96% and within the lactation period 84% of the women consumed at least 1 natural remedy. Phytotherapeutic drugs were used most frequently. In contrast to the widespread use of natural remedies by pregnant women and nursing mothers in this study, little information on the effectiveness and possible risks is available. Therefore it seems necessary to examine and evaluate natural remedies used during pregnancy and lactation.