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

Abstract

BackgroundThe 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).MethodsMyometrium 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.ResultsBPJ (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.ConclusionsBPJ 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.

Identification of mundulone and mundulone acetate as natural products with tocolytic efficacy in mono- and combination-therapy with current tocolytics

“…However, when combined with atosiban the TI of mundulone dramatically improved to a favorable TI = 10, and therefore, shows potential for combination with current tocolytics. To this end, at least one other study reported improved inhibition of uterine contractility when another flavonoid containing plant extract from Bryophyllum pinnatum was combined with atosiban or nifedipine [18]. In our study, the ex vivo tocolytic efficacy and potency of mundulone in combination with atosiban significantly improved using term-pregnant mouse and human myometrial tissue.…”

“…Moreover, a recent review on natural products for tocolysis found that most plant extracts for inhibition of uterine contractions belong to flavonoid or terpene classes [16]. Interestingly, plant extracts containing flavonoids have shown tocolytic effects (J. flava, B. pinnatum, T. paniculatum), with B. pinnatum entering into a clinical trial that was, unfortunately, withdrawn early due to lack of patient enrollment [17][18][19][20][21][22]. Therefore, mundulone and MA belong to an interesting class of compounds to study for tocolytic potential.…”

Bryophyllum pinnatum Compounds Inhibit Oxytocin-Induced Signaling Pathways in Human Myometrial Cells

“…Using the myograph model, we previously showed that BPJ concentration-dependently inhibits spontaneous myometrium contractions, affecting their peak, tension, and duration ( Fürer et al, 2016 ; Santos et al, 2019a ). Stronger effects on spontaneous contractility were observed when BPJ was combined with atosiban ( Santos et al, 2019b ). However, a comparison of findings in these models should be done with caution given that the modulation of contractility in myometrium strips is a much more complex process than what can be investigated with a cell line.…”

“…Several clinical studies have shown a very good tolerability of B. pinnatum preparations for this ( Plangger et al, 2006 ; Fürer et al, 2015b ; Simões-Wüst et al, 2018 ) and other indications ( Betschart et al, 2013 ; Lambrigger-Steiner et al, 2014 ). In vitro studies showed that B. pinnatum reduces the strength of human myometrium contractions ( Santos et al, 2019a ; Santos et al, 2019b ). In human myometrial cells (hTERT-C3 cell line), leaf press juice of B. pinnatum (BPJ) lowered the OT-induced increase of intracellular calcium concentrations [(Ca 2+ ) i ] ( Simões-Wüst et al, 2010 ).…”

Effects of <b><i>Bryophyllum pinnatum</i></b> Administration on Wistar Rat Pregnancy: Biochemical and Histological Aspects

“…B. pinnatum is known to act on uterine contractility. In vitro research with human myometrial cells has been conducted at university centers in Switzerland since the early 2000s [3,29,30,55,56]. Several clinical studies have also evaluated the tocolytic effect of B. pinnatum in premature labor [44,45,57].…”