Bryophyllum pinnatum fractions inhibit the oxytocin-induced increase of intracellular calcium concentration in human myometrial cells

Bryophyllum pinnatum is used in the treatment of premature labour [1]. Previous work with myometrial cells showed that B. pinnatum juice (BPJ) inhibits the increase of intracellular calcium concentration ([Ca²⁺]_i) induced by oxytocin (OT) [2]. We here compared the effects on this increase of BPJ, a bufadienolide-enriched fraction (BEF [3]), a flavonoid-enriched fraction (FEF [3]), the corresponding flavonoid aglycon mixture (A-Mix [3]), bersaldegenin-1,3,5-orthoacetate (BO), and the combination of BEF and FEF.

hTERT-C3 and PHM1-41 cells loaded with a calcium specific fluorescent probe were pre-incubated with test substances and stimulated with OT. [Ca²⁺]_i was measured by real-time fluorescence spectrophotometry. Atosiban was used as a positive control.

BPJ led to concentration-dependent decrease of the OT-induced increase of [Ca²⁺]_i in both cell lines (p<0.0001), achieving ca. 75% inhibition at 20 µg/mL concentration. BEF, FEF, BO, A-Mix, and the combination of BEF and FEF led to a concentration-dependent decrease of the OT-induced increase of [Ca²⁺]_i in hTERT-C3 cells (p<0.05). BEF (2.2 µg/mL), FEF (17.4 µg/mL), BO (0.04 µg/mL), and A-Mix (0.7 µg/mL), at concentrations corresponding to 20 µg/mL BPJ led to ca. 25% decrease of the OT-induced increase of [Ca²⁺]_i. The combination of BEF plus FEF led to a decrease of 55.3%.

In conclusion, the data confirm previous observations showing that BPJ promotes a specific and concentration-dependent effect on the OT signalling pathway. Compounds present in BEF and in FEF seem to have a synergistic effect on the inhibition of the oxytocin-induced increase of [Ca²⁺]_i, which is similar to the effect of BPJ.

• References

• 1 Fürer K, Simões-Wüst AP, von Mandach U, Hamburger M, Potterat O. Bryophyllum pinnatum and related species used in anthroposophic medicine: constituents, pharmacological activities, and clinical efficacy. Planta Med 2016; 82: 930-941.
• 2 Simões-Wüst AP, Grãos M, Duarte CB, Breinneisen R, Hamburger M, Mennet M. et al. Juice of Bryophyllum pinnatum (Lam.) inhibits oxytocin-induced increase of the intracellular calcium concentration in human myometrial cells. Phytomedicine 2010; 17: 980-986.
• 3 Santos S, Haslinger C, Klaic K, Faleschini MT, Mennet M, Potterat O. et al. A bufadienolide-enriched fraction of Bryophyllum pinnatum inhibits human myometrial contractility in vitro . Planta Med 2019; 85: 385-393.