TABLE 2.
Methodological characteristics, plant material, main results of included publications on anti-contractility and smooth muscle relaxing effects of B. pinnatum.
| Reference | Title | Type of study | Bryophyllum pinnatum material | Main outcome assessment | Main results |
|---|---|---|---|---|---|
| Gwehenberger et al. (2004) | Effect of Bryophyllum pinnatum versus fenoterol on uterine contractility | Ex vivo organ bath model with (human) myometrial biopsies from term caesarean section compared to fenoterol | Leaf press juice and 5% leaf press juice solution for i.v. injection | (A) Effect on spontaneous contractions | (A) Concentration-dependent reduction in area under the curve (AUC; maximal by 16% at 104 mg/L); increase in contraction frequency |
| (B) Effect on OT-induced contraction | (B) Maximal reduction of AUC by 20% at 5 × 103 mg/L; decreased contraction frequency at 5 × 103 mg/L | ||||
| Mans et al. (2004) | Assessment of eight popularly used plant-derived preparations for their spasmolytic potential using the isolated guinea pig ileum | Ex vivo organ bath model on ability to reduce the strength of smooth muscle contraction in guinea pig ileum | Aqueous leaf extract | (A) Effect on contraction induced by acetylcholine | (A) Inhibitory effect on acetylcholine-induced contractions only observed at 10 mg/mL |
| (B) Effect on contraction induced by histamine | (B) Dose dependent inhibitory effect on contraction force induced by histamine (40%–95% at doses from 0.01 to 10 mg/mL) | ||||
| Plangger et al. (2006) | Intravenous tocolysis with Bryophyllum pinnatum is better tolerated than beta-agonist application | Retrospective matched-pair study on tocolytic effect of i.v. infused B. pinnatum compared to beta-agonist (n = 134) | 5% leaf press juice solution for i.v. injection | (A) Prolongation of pregnancy | (A) Equal in the prolongation of pregnancy and (B) Gestational age at delivery |
| (B) Gestational age at delivery | |||||
| (C) Maternal tolerability | (C) Fewer adverse effect in the Bryophyllum group (p = 0.02 a ) | ||||
| Ozolua et al. (2010) | Effects of aqueous leaf extract of Bryophyllum pinnatum on guinea pig tracheal ring contractility | Ex vivo organ bath model on effect on contractile responses of isolated guinea pig tracheal rings | Aqueous leaf extract | (A) Effect on histamine-induced contraction | 0.25–1.0 mg/mL of the extract in organ baths significantly reduced the maximal contractile responses induced by (A) histamine and (B) carbachol |
| (B) Effect on carbachol-induced contraction | |||||
| Simões-Wüst et al. (2010) | Juice of Bryophyllum pinnatum (Lam.) inhibits oxytocin-induced increase of the intracellular calcium concentration in human myometrial cells | In vitro intracellular free calcium assay in human myometrial cell line | Leaf press juice | Effect on OT-induced increase of intracellular calcium in human myometrial cells | Press juice prevented the OT-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 |
| Wächter et al. (2011) | Leaf press juice from Bryophyllum pinnatum (Lamarck) Oken induces myometrial relaxation | Ex vivo organ bath model with myometrial biopsies from term cesarean section | Leaf press juice and MPLC fractions | (A) Effect on amplitude of contraction | (A) Amplitude reduced to 78% of baseline after second addition of 2 μL press juice; reduced to 70% after second addition of a fraction tentatively assigned to flavonoids |
| (B) Effect on AUC of contraction | (B) AUC reduced to 82% after first addition of 2 μL press juice; reduced to 51% after first addition of fraction tentatively assigned to flavonoids | ||||
| Schuler et al. (2012) | Bryophyllum pinnatum inhibits detrusor contractility in porcine bladder strips - A pharmacological study towards a new treatment option of overactive bladder | Ex vivo organ bath model porcine detrusor strips compared to oxybutynin | Leaf press juice | (A) Inhibitory effect measurements with electrical field stimulation (B) Relaxant effect measurements on carbachol pre-contracted strips |
(A) Press juice 5% inhibited electrically induced contractions by 75% relative to time-matched control (B) Press juice 10% maximum relaxant effect on carbachol re-contracted strips was 19% |
| Betschart et al. (2013) | Randomized, double-blind placebo-controlled trial with Bryophyllum pinnatum versus placebo for the treatment of overactive bladder in postmenopausal women | RCT vs placebo (n = 20) | Leaf press juice tablets 50% | (A) Reduction of micturition frequency per 24 h | (A) Trend in reduction of micturition frequency per 24 h from 9.5 to 7.8 |
| (B) Quality of life | (p = 0.064) | ||||
| (B) Improvement of quality of life did not differ between the two groups | |||||
| Fürer et al. (2015a) | Inhibition of porcine detrusor contractility by the flavonoid fraction of Bryophyllum pinnatum--a potential phytotherapeutic drug for the treatment of the overactive bladder syndrome | Ex vivo organ bath model measuring repeated electrically induced contractions of porcine detrusor strips | Leave press juice and fractions prepared from methanolic leaf extract | (A) Effect of press juice | (A) After initial stimulation, press juice 10% led to a reduction of detrusor contractility to 59% |
| (B) Effect of a fraction enriched in flavonoids | (B) After initial stimulation, a fraction enriched in flavonoids showed a significant reduction of the contractility to 21% at a concentration of 1 mg/mL | ||||
| (C) Effect of a fraction enriched in bufadienolides | (C) A fraction enriched in bufadienolides had stimulatory effects (max. concentration tested 40 μg/mL) | ||||
| Mans et al. (2015) | Evaluation of surinamese medicinal plants for their potential bronchospasmolytic effects in isolated guinea pig tracheal chains | Ex vivo organ bath model on effect on contractile responses of isolated guinea pig tracheal rings | Aqueous leaf extract | (A) Effect on acetylcholin-induced contraction | Aqueous extract (10 mg/mL) reduced the force of contraction of the tracheal chains caused by both (A) acetylcholine and (B) histamine by 40%–70% |
| (B) Effect on histamine-induced contraction | |||||
| Bachmann et al. (2017) | Potential of Bryophyllum pinnatum as a detrusor relaxant: an in vitro exploratory study | Ex vivo organ bath model measuring KCl-induced contractility of porcine detrusor strips | Leaf press juice, fractions enriched in flavonoids or bufadienolides, flavonoid aglycon mix | (A) Effect of leaf press juice on contraction force | (A) Press juice increased the contraction force |
| (B) Effect of bufadienolide- and (C) Flavonoide-enriched fractions on contractions force | (B) A purified bufadienolide-enriched fraction (0.1–1.0 mg/mL) led to significant inhibition of detrusor contractility | ||||
| (C) A flavonoid-enriched fraction did not affect contraction force and flavonoid aglycons (0.15–0.5 mg/mL) led to a concentration-dependent lowering of the contraction force | |||||
| Santos et al. (2018) | A bufadienolide-enriched fraction of Bryophyllum pinnatum inhibits human myometrial contractility in vitro | Ex vivo organ bath model with myometrial biopsies from term cesarean section | Leaf press juice, fractions enriched in flavonoids or bufadienolides, flavonoid aglycon mix | (A) Effect of leaf press juice on contraction strength | (A) 10 mg/mL of leave press juice |
| (B) Effect of bufadienolide- and (C) Flavonoide-enriched fractions and aglycon mix on contractions strength | (B) 1 μg/mL bufadienolide-enriched fraction | ||||
| (C) 150 μg/mL of flavonoid-enriched fraction and 6.2 μg/mL of flavonoid aglycon mixture lead to reduction of contraction strength of about 40% | |||||
| Simões-Wüst et al. (2018) | Two randomised clinical trials on the use of Bryophyllum pinnatum in preterm labor: results after early discontinuation | Trial I: RCT vs placebo (double blind; n = 26) Trial II: RCT vs nifedipine (open-label; n = 27) | Trial I: ethanolic tincture 33% | (A) Trial I: prophylaxis of preterm labor in patients at risk | (A) and (B) Trials discontinued early due to slow patient recruitments, data not sufficient for concluisions on efficacy |
| Trial II: leaf press juice tablets 50% | (B) Difference in patient response to tocolysis | (C) Overall a good tolerability was observed | |||
| (C) Tolerability | |||||
| Santos et al. (2019) | Bryophyllum pinnatum enhances the inhibitory effect of atosiban and nifedipine on human myometrial contractility: An in vitro study | Ex vivo organ bath model with (human) myometrial biopsies from term cesarean section viability assays in human myometrial cells | Leaf press juice | (A) Effect on contraction strength in combination with standard tocolytics | (A) Press juice plus atosiban promoted a decrease to 49%; press juice and atosiban alone lowered it to 71% and 81%, respectively. Press juice plus nifedipine decreased strength to 40%, press juice and nifedipine alone lowered it to 79% and 71% (B) Test substances showed no effect on cell viability |
| (B) Cell toxicity | |||||
| Santos et al. (2021) | Bryophyllum pinnatum compounds inhibit oxytocin-induced signaling pathways in human myometrial cells | In vitro cell signaling assays in human myometrial cells | Leaf press juice, fractions enriched in flavonoids or bufadienolides, flavonoid aglycon mix | (A) Effect on OT-stimulated intracellular calcium increase | (A) Concentration-dependent decrease of OT-induced increase of intracellular free calcium concentration was observed for all test substances but none of them was as strong as press juice (inhibition of 70%); significant inhibition was obtained with 4.335 μg/mL of flavonoid fraction and 0.055 μg/mL bufadienolide fraction (B) inhibition of OT-driven activation of MAPKs ERK1/2 and SAPK/JNK by press juice and bufadienolide-enriched fraction |
| (B) Effect on OT-driven activation of MAPKs | |||||
| Mirzayeva et al. (2023) | Bryophyllum pinnatum and improvement of nocturia and sleep quality in women: a multicentre, nonrandomized prospective trial | Multicenter, nonrandomized prospective clinical trial (n = 49) | Leaf press juice tablets 50% | (A) Nocturia (voids per night) | (A) Nocturia diminished from 3.2 to 2.3 voids per night (p < 0.001) |
| (B) Sleep disorders (PSQI score) | (B) PSQI score decreased from 7.7 to 6.6 (p = 0.004) |
a
Only in case of clinical studies p-values are shown.