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

Stefanie Santos,Ana Paula Simões-Wüst,Olivier Potterat,Mónica Mennet,Leonie Zurfluh,Ursula Von Mandach,Matthias Hamburger

doi:10.3389/fphar.2021.632986

Abstract

Bryophyllum pinnatum has been used in the treatment of premature labor, first in anthroposophic hospitals and, recently, in conventional settings as an add-on medication. In vitro work with hTERT human myometrial cells showed that B. pinnatum leaf press juice inhibits the increase of intracellular free calcium concentration induced by oxytocin, a hormone known to play a role in labor. Our aim was to identify fractions/compounds in B. pinnatum press juice that contribute to this inhibitory effect, and to investigate their effect on oxytocin-driven activation of the MAPK cascade. Several fractions/compounds from B. pinnatum press juice led to a concentration-dependent decrease of oxytocin-induced increase of intracellular free calcium concentration, but none of them was as strong as B. pinnatum press juice. However, the combination of a bufadienolide and a flavonoid-enriched fraction was as effective as B. pinnatum press juice, and their combination had a synergistic effect. B. pinnatum press juice inhibited oxytocin-driven activation of MAPKs SAPK/JNK and ERK1/2, an effect also exerted by the bufadienolide-enriched fraction. The effect of B. pinnatum press juice on oxytocin-induced signaling pathways was comparable to that of the oxytocin-receptor antagonist and tocolytic agent atosiban. Our findings further substantiate the use of B. pinnatum press juice preparations in the treatment of preterm labor.

Highlights

Every year, around 15 million neonates worldwide are born too early
The combination of Bufadienolide-enriched fraction (BEF) and Flavonoide-enriched fraction (FEF) has an effect on the canonical signaling pathway that is comparable to that of Bryophyllum pinnatum Leaf Press Juice (BPJ), and the combination of these fractions enriched in bufadienolides (BEF) and flavonoid glycosides (FEF) is synergistic
Another OT-induced pathway, namely the activation of the mitogen-activated protein kinase (MAPK) SAPK/JNK and extracellular signal-regulated kinases 1 and 2 (ERK1/2) is inhibited by BPJ, whereby the bufadienolide fraction seems to be responsible for the inhibition of ERK1/2 phosphorylation, and the combination of BEF plus FEF for the inhibition of SAPK/JNK phosphorylation

Summary

Introduction

Prematurity, (i.e. birth before 37 weeks of pregnancy) is the number one cause of neonatal deaths, and the leading cause of death in children under 5 years of age. A number of pharmacological agents known as tocolytics—including beta-sympathomimetic drugs, oxytocin receptor (OTR) antagonists, and calcium channel. Treatment with the usual tocolytic agents is often accompanied by various, in part serious side-effects. These include tachycardia, dyspnea, palpitation, pulmonary edema, and hyperglycemia [in the case of the sympathomimetic drugs (Arrowsmith et al, 2010)], nausea, dizziness, headache, and tachycardia [OTR antagonists (Flenady et al, 2014a)] and flushing, hypotension, and suppression of heart rate [calcium channel blockers (Flenady et al, 2014b)]

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