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The medicinal plant Bryophyllum pinnatum was previously shown to block oxytocin (OT)-induced signals in myometrial cells, consistent with its tocolytic effect observed in patients. OT activates not only OT receptors but also V1A receptors, two receptors with high receptor homology that are both expressed in the myometrium and play a crucial role in myometrial contraction signaling. We aimed to study the molecular pharmacology of B. pinnatum herbal preparations using specific receptor ligands, the human myometrial cell line hTERT-C3, and cell lines expressing recombinant human OT and V1A receptors. We found that press juice from B. pinnatum (BPJ) inhibits both OT- and vasopressin (AVP)-induced intracellular calcium increases in hTERT-C3 myometrial cells. In additional assays performed with cells expressing recombinant receptors, BPJ also inhibited OT and V1A receptor-mediated signals with a similar potency (IC50 about 0.5 mg/mL). We further studied endogenous OT- and AVP-sensitive receptors in hTERT-C3 cells and found that OT and AVP stimulated those receptors with similar potency (EC50 of ~ 1 nM), suggesting expression of both receptor subtypes. This interpretation was corroborated by the antagonist potencies of atosiban and relcovaptan that we found. However, using qPCR, we almost exclusively found expression of OT receptors suggesting a pharmacological difference between recombinant OT receptors and native receptors expressed in hTERT-C3 cells. In conclusion, we show that B. pinnatum inhibits both OT and AVP signaling, which may point beyond its tocolytic effects to other indications involving a disbalance in the vasopressinergic system. [ABSTRACT FROM AUTHOR]

The placental passage of protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, 2 compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. The study compound did not affect placental viability or functionality, as glucose consumption, lactate production, and beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings. [ABSTRACT FROM AUTHOR]

Pregnancy is a critical period for medical care, during which the well-being of woman and fetus must be considered. This is particularly relevant in managing non-psychotic mental disorders since treatment with central nervous system-active drugs and untreated NMDs may have negative effects. Some well-known herbal preparations (phytopharmaceuticals), including St. Johnʼs wort, California poppy, valerian, lavender, and hops, possess antidepressant, sedative, anxiolytic, or antidepressant properties and could be used to treat mental diseases such as depression, restlessness, and anxiety in pregnancy. Our goal was to assess their safety in vitro , focusing on cytotoxicity, induction of apoptosis, genotoxicity, and effects on metabolic properties and differentiation in cells widely used as a placental cell model (BeWo b30 placenta choriocarcinoma cells). The lavender essential oil was inconspicuous in all experiments and showed no detrimental effects. At low-to-high concentrations, no extract markedly affected the chosen safety parameters. At an artificially high concentration of 100 µg/mL, extracts from St. Johnʼs wort, California poppy, valerian, and hops had minimal cytotoxic effects. None of the extracts resulted in genotoxic effects or altered glucose consumption or lactate production, nor did they induce or inhibit BeWo b30 cell differentiation. This study suggests that all tested preparations from St. Johnʼs wort, California poppy, valerian, lavender, and hops, in concentrations up to 30 µg/mL, do not possess any cytotoxic or genotoxic potential and do not compromise placental cell viability, metabolic activity, and differentiation. Empirical and clinical studies during pregnancy are needed to support these in vitro data. [ABSTRACT FROM AUTHOR]

The placental passage of humulone and protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, 2 compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Only a small portion of humulone initially present in the maternal circuit reached the fetal circuit. The humulone concentration in the maternal circuit rapidly decreased, likely due to metabolization in the placenta. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. None of the study compounds affected placental viability or functionality, as glucose consumption, lactate production, beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings. [ABSTRACT FROM AUTHOR]

Bryophyllum pinnatum has been used since the 1970s to prevent premature labour, first in anthroposophic hospitals and, more recently, also in the main Swiss perinatal centres. However, it is not known which compounds in B. pinnatum leaves contribute to the tocolytic effect. Here we studied the effects of a flavonoid-enriched fraction, the corresponding flavonoid aglycon mixture, a bufadienolide-enriched fraction, and B. pinnatum leaf press juice on human myometrial contractility in vitro. The strength (area under the curve and amplitude) and frequency of contractions were recorded using strips of human myometrium mounted in an organ bath system. Cell viability assays were performed with the human myometrium hTERT-C3 and PHM1 – 41 cell lines. Repeated addition of the flavonoid-enriched fraction, flavonoid aglycon mixture, bufadienolide-enriched fraction, or B. pinnatum leaf press juice led to a progressive decrease of contraction strength, without jeopardising the vitality of myometrium strips. The bufadienolide-enriched fraction was the most active, since 1 µg/mL of the bufadienolide-enriched fraction lowered the area under the curve to 40.1 ± 11.8% of the initial value, whereas 150 µg/mL of the flavonoid-enriched fraction, 6.2 µg/mL of the flavonoid aglycon mixture, and 10 µg/mL of the B. pinnatum leaf press juice were required to achieve comparable inhibition. A progressive increase of contraction frequency was observed, except in the case of the flavonoid aglycon mixture, which did not affect frequency. None of the test substances decreased myometrial cell viability, even at concentrations of 500 µg/mL of the flavonoid-enriched fraction, 40 µg/mL of the flavonoid aglycon mixture, 3.8 µg/mL of the bufadienolide-enriched fraction, and 75 µg/mL of the B. pinnatum leaf press juice, i.e., higher than those used in the myometrium experiments. Given the concentrations of flavonoids in the flavonoid-enriched fraction and B. pinnatum leaf press juice, and of bufadienolides in the bufadienolide-enriched fraction and B. pinnatum leaf press juice, it appears that bufadienolides may be mainly responsible for the relaxant effect. [ABSTRACT FROM AUTHOR]

An earlier prospective, randomised, placebo-controlled clinical trial had suggested that Bryophyllum pinnatum might have potential in the treatment of overactive bladder. Here we investigated the effects of B. pinnatum leaf press juice, fractions enriched in flavonoids and bufadienolides, and a flavonoid aglycon mixture and individual aglycons on detrusor contractility as a major target in overactive bladder treatment. The strength of the detrusor contractions was investigated using porcine muscle strips stimulated with KCl. B. pinnatum leaf press juice increased the contraction force of muscle strips. Treatment with the flavonoid-enriched fraction had almost no effect on contractility, while the bufadienolide-enriched fraction and flavonoid aglycons led to a concentration-dependent lowering of the contraction force. The data indicate that several components of B. pinnatum leaf press juice may contribute to the inhibitory effect on detrusor contractility, which in turn provides support to overactive bladder treatment with B. pinnatum. [ABSTRACT FROM AUTHOR]

Bryophyllum pinnatum is a succulent perennial plant native to Madagascar which is used in anthroposophical medicine to treat psychiatric disorders and as a tocolytic agent to prevent premature labour. We performed a metabolite profiling study in order to obtain a comprehensive picture of the constituents in B. pinnatum leaves and to identify chromatographic markers for quality control and safety assessment of medicinal preparations. Preliminary HPLC-PDA-ESIMS analyses revealed that flavonoid glycosides were the main UV-absorbing constituents in the MeOH extract of B. pinnatum. Two phenolic glucosides, syringic acid β-D-glucopyranosyl ester (1) and 4'-O- β -D-glucopyranosyl-cis-p-coumaric acid (2), as well as nine flavonoids (3-11) including kaempferol, quercetin, myricetin, acacetin, and diosmetin glycosides were unambiguously identified by 1H and 2D NMR analysis after isolation from a MeOH extract. The flavonol glycosides quercetin 3-O-α-L-arabinopyranosyl-(1 → 2)-α-L-rhamnopyranoside 7-O-β-D-glucopyranoside (3) and myricetin 3-O-α-L-arabinopyranosyl-(1 → 2)-α-L-rhamnopyran-oside (4) were new natural products. With the aid of HPLC-PDA-APCIMS and authentic references isolated from the related species B. daigremontia-num, the presence of four bufadienolides, bersal-degenin-1 -acetate (12), bryophy llin A (13), bersal-degenin-3-acetate (14), and bersaldegenin-1,3,5-orthoacetate (15) was detected in B. pinnatum. [ABSTRACT FROM AUTHOR]

The placental passage of humulone and protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, 2 compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Only a small portion of humulone initially present in the maternal circuit reached the fetal circuit. The humulone concentration in the maternal circuit rapidly decreased, likely due to metabolization in the placenta. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. None of the study compounds affected placental viability or functionality, as glucose consumption, lactate production, beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings. [ABSTRACT FROM AUTHOR]