Bryophyllin B

Bryophyllin B at a Glance

Bryophyllin B is a bufadienolide — one of the cardiac-glycoside-class steroids that give Kalanchoe pinnata (Bryophyllum pinnatum) its toxicity. It was isolated in 1989 and described, in a natural-products series looking for antitumour agents, as a potent cytotoxic bufadienolide ^{1Reference 1Yamagishi T et al. · 1989In vitroAntitumor agents, 110View study →}. The same report showed it can be produced from bryotoxin C — the compound also known as bryophyllin A — by acid treatment ^{1,2Reference 1Yamagishi T et al. · 1989In vitroAntitumor agents, 110View study →Reference 2Yamagishi T et al. · 1988In vitroStructure and stereochemistry of bryophyllin-A, a novel potent cytotoxic bufadienolide orthoacetate from Bryophyllum pinnatum — in vitroView study →}.

Bufadienolides work the way digoxin works: they bind and inhibit the sodium–potassium ATPase, the pump that maintains the ionic gradient across every animal cell membrane. In a cultured cell that reads as cytotoxicity; in a heart it reads as arrhythmia and myocardial necrosis ^{10Reference 10Sousa LQ et al. · 2017ReviewBufadienolides from amphibians: A promising source of anticancer prototypes for radical innovation, apoptosis triggering and Na(+)/K(+)-ATPase inhibition — reviewView study →}. These are not two properties with a trade-off between them. They are one property with two names.

The evidence for what this class does to a whole animal is unusually good, and it comes from veterinary pathology rather than pharmacology. Between 1960 and 1984, Bryophyllum species caused 41 recorded poisoning incidents affecting 379 cattle in Queensland, with myocardial degeneration and necrosis as the life-threatening lesion ^{4Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study →}. That is the frame this molecule belongs in.

What a Bufadienolide Does

Bufadienolides are C24 steroids carrying a six-membered α-pyrone ring at C17. Structurally and functionally they are the amphibian-and-plant counterpart of the cardenolides — digoxin and digitoxin — and they act at the same target.

The mechanism is Na⁺/K⁺-ATPase inhibition. Bufadienolides bind the pump in a manner structurally analogous to the digoxin– and ouabain–ATPase complexes, and the consequences follow the cardiac-glycoside script: intracellular sodium rises, the sodium–calcium exchanger runs less effectively, calcium accumulates, contractility increases and then conduction destabilises ^{10Reference 10Sousa LQ et al. · 2017ReviewBufadienolides from amphibians: A promising source of anticancer prototypes for radical innovation, apoptosis triggering and Na(+)/K(+)-ATPase inhibition — reviewView study →}. Downstream, the class also triggers mitochondrial depolarisation, cytochrome-c release, caspase activation, PARP cleavage and cell-cycle arrest — the apoptotic cascade that gets written up as anticancer activity ^{10Reference 10Sousa LQ et al. · 2017ReviewBufadienolides from amphibians: A promising source of anticancer prototypes for radical innovation, apoptosis triggering and Na(+)/K(+)-ATPase inhibition — reviewView study →}.

Species differences make the animal data hard to transfer, in both directions. Bufadienolides show weaker activity on murine cells than on human ones, attributed to structural differences between the mouse and human ATPase subunits ^{10Reference 10Sousa LQ et al. · 2017ReviewBufadienolides from amphibians: A promising source of anticancer prototypes for radical innovation, apoptosis triggering and Na(+)/K(+)-ATPase inhibition — reviewView study →}. A rodent tolerance result therefore under-predicts human sensitivity — the opposite of the usual reassuring direction.

Human bufadienolide poisoning is documented, and it is cardiac. Six previously healthy men who ingested a topical preparation containing Chan Su — a traditional Chinese medicine made from toad venom, a bufadienolide source — developed vomiting and bradycardia; four died of cardiac dysrhythmias, and the two who survived did so after treatment with digoxin-specific Fab fragments ^{11Reference 11Brubacher JR et al. · 1996Case reportTreatment of toad venom poisoning with digoxin-specific Fab fragments — case reportView study →}. Their apparent digoxin assays were positive, which is the practical point: bufadienolide poisoning presents as, and cross-reacts with, digoxin toxicity.

There is a second, slower form of bufadienolide poisoning worth distinguishing. In South Africa, Cotyledon, Tylecodon and Kalanchoe species cause “krimpsiekte” — a chronic paretic/paralytic condition from cumulative neurotoxic bufadienolides (cotyledoside, the tyledosides, orbicusides and lanceotoxins), a different structural subgroup from the bryophyllins, and one whose residues in edible tissues from affected animals pose a documented risk to people ^{12Reference 12Botha C · 2016ReviewPotential Health Risks Posed by Plant-Derived Cumulative Neurotoxic Bufadienolides in South Africa — reviewView study →}.

The Livestock Poisonings

The Bryophyllum poisoning literature is the best whole-animal evidence this compound class has, and it is precise about dose, season and plant part.

Flowering plants are the dangerous form. In the Queensland series, poisoning occurred between May and October — the flowering season — and flowers were the most toxic part by a wide margin. The median lethal doses of B. tubiflorum were 0.7 g dry matter/kg liveweight for flowers, 2.3 g/kg for roots and 5.0 g/kg for leaf plus stem ^{4Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study →}. Cattle showed anorexia, depression, ruminal atony, diarrhoea, heart-rate and rhythm abnormalities, dyspnoea and death, with myocardial degeneration and necrosis plus cardiac and alimentary haemorrhage at post-mortem ^{4Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study →}.

The toxicity tracks measured bufadienolide content, but not completely. A follow-up study dosed calves with flower heads or whole plants of six Bryophyllum species and assayed bryotoxins A, B and C by HPLC. Toxicity ran, in descending order, the B. daigremontianum × B. tubiflorum hybrid, then B. pinnatum, then B. tubiflorum, B. fedtschenkoi, B. daigremontianum and B. proliferum. Comparing the calf results with the assays, the authors concluded the bryotoxins probably account for the disease — but that B. pinnatum and B. fedtschenkoi contain at least one further cardiac glycoside not covered by the assay ^{5Reference 5McKenzie RA et al. · 1987The toxicity to cattle and bufadienolide content of six Bryophyllum species — animal studyView study →}. B. fedtschenkoi poisoned calves with no bryotoxins detectable at all.

Species identification matters more than dose here. Content varies markedly between Kalanchoe species and between plant parts; the predominant bufadienolide differs from species to species, and B. tubiflorum leaves carry very little of the compounds that dominate B. daigremontianum leaves ^{6Reference 6Oufir M et al. · 2015Quantification of Bufadienolides in Bryophyllum pinnatum Leaves and Manufactured Products by UHPLC-ESIMS/MSView study →}. An ornamental Kalanchoe is not interchangeable with the medicinal one.

What It's Used For

Bryophyllin B itself has one primary paper. Everything else here is the class it belongs to, and the class is where the useful information is.

Its two siblings in the same plant have been studied a little further, and both results point the same way. Of five Kalanchoe bufadienolides screened against phorbol-ester-induced Epstein–Barr virus early-antigen activation, bryophyllin A was the most active at IC50 0.4 µM, with bryophyllin C — its reduction analogue — and bersaldegenin-3-acetate weaker ^{13Reference 13Supratman U et al. · 2001In vitroAnti-tumor promoting activity of bufadienolides from Kalanchoe pinnata and K. daigremontiana x tubiflora — in vitroView study →}.

And bryophyllin C is frankly insecticidal, killing third-instar silkworm larvae at an LD50 of 5 µg per gram of diet, against 3 µg/g for bryophyllin A ^{3Reference 3Supratman U et al. · 2000AnimalNew insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata — in vivo insect assayView study →}.

A compound class that kills insects, kills cultured cells and stops cattle hearts is expressing one property in three assays.

Evidence by IndicationStrength of support · Beta

01Cardiac Glycoside ToxicityPromising48%Class-level: Na⁺/K⁺-ATPase mechanism, controlled cattle dosing with content assays, fatal human bufadienolide poisonings ^{4,5,10,11Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study →Reference 5McKenzie RA et al. · 1987The toxicity to cattle and bufadienolide content of six Bryophyllum species — animal studyView study →Reference 10Sousa LQ et al. · 2017ReviewBufadienolides from amphibians: A promising source of anticancer prototypes for radical innovation, apoptosis triggering and Na(+)/K(+)-ATPase inhibition — reviewView study →Reference 11Brubacher JR et al. · 1996Case reportTreatment of toad venom poisoning with digoxin-specific Fab fragments — case reportView study →}

02Cytotoxicity in Cancer Cell LinesShaky16%A single 1989 isolation report describing the compound as potently cytotoxic, with no follow-up in thirty-five years ^{1Reference 1Yamagishi T et al. · 1989In vitroAntitumor agents, 110View study →}

Mechanisms

One row is doing all the work. A compound that stops the sodium pump does not choose which cell it stops it in.

Pharmacokinetics

None published for bryophyllin B, in any species. The only exposure-relevant datum for the class in this plant is dermal: after Kalanchoe juices were applied to a skin-barrier model, no bufadienolide was detected in the subcutaneous filtrate — the compounds did not cross ^{14Reference 14Hering A et al. · 2025In vitroBufadienolide Penetration Through the Skin Membrane and Antiaging Properties of Kalanchoe sppView study →}. That speaks to topical cosmetic use and says nothing about oral intake.

Clinical Trials

None. The clinical literature on Bryophyllum pinnatum concerns the standardised 50% leaf press juice used in anthroposophic obstetrics, not any isolated bufadienolide ^{7Reference 7Fürer K et al. · 2016ReviewBryophyllum pinnatum and Related Species Used in Anthroposophic Medicine: Constituents, Pharmacological Activities, and Clinical Efficacy — reviewView study →}.

Last checked: September 2026.

Isolate vs. Plant Studies

The isolate record is one paper. The plant record is far larger and points in an instructive direction: the useful activities and the dangerous chemistry in B. pinnatum are physically separable, and someone separated them. When fractions of the leaf were tested on porcine detrusor muscle, the flavonoid fraction reduced contractility to 21.3% of baseline — comparable to oxybutynin — while the bufadienolide fraction had no inhibitory effect at the concentrations tested ^{9Reference 9Fürer K et al. · 2015In vitroInhibition of porcine detrusor contractility by the flavonoid fraction of Bryophyllum pinnatum—a potential phytotherapeutic drug for the treatment of the overactive bladder syndrome — in vitroView study →}.

The obstetric use runs the other way. On human myometrial strips, a bufadienolide-enriched fraction was the most active tocolytic tested by two orders of magnitude — 1 µg/mL lowering the area under the contraction curve to 40% of baseline, against 150 µg/mL of the flavonoid fraction for comparable inhibition — without reducing myometrial cell viability ^{8Reference 8Santos S et al. · 2019In vitroA Bufadienolide-Enriched Fraction of Bryophyllum pinnatum Inhibits Human Myometrial Contractility In VitroView study →}. So the class is not inert in a useful direction either. But that is a fraction, in vitro, on isolated tissue; the preparation with actual human use is the whole standardised press juice ^{7Reference 7Fürer K et al. · 2016ReviewBryophyllum pinnatum and Related Species Used in Anthroposophic Medicine: Constituents, Pharmacological Activities, and Clinical Efficacy — reviewView study →}, and no isolated bufadienolide has ever been given to a person deliberately.

Prevalence in Nature

Bryophyllin B occurs in Kalanchoe pinnata (Bryophyllum pinnatum), a succulent native to Madagascar and naturalised widely through the tropics and subtropics. Beyond that, its distribution is uncharacterised — no survey has looked for it across the genus.

The class context is better quantified. Total bufadienolide content of B. pinnatum leaf ranges 16.3–40.5 mg/100 g dry weight in Brazilian-grown plants and only 3.8–12.5 mg/100 g in German-grown ones, with press juices at 0.89–1.16 and 0.09–0.16 mg/100 mL respectively; content is markedly higher in young leaves ^{6Reference 6Oufir M et al. · 2015Quantification of Bufadienolides in Bryophyllum pinnatum Leaves and Manufactured Products by UHPLC-ESIMS/MSView study →}. Across the genus the predominant compound changes with species — bersaldegenin-1,3,5-orthoacetate dominates B. daigremontianum leaf and B. tubiflorum stem, while B. tubiflorum leaves carry very little of any of them ^{6Reference 6Oufir M et al. · 2015Quantification of Bufadienolides in Bryophyllum pinnatum Leaves and Manufactured Products by UHPLC-ESIMS/MSView study →}. Flowers carry the highest toxicity of any part, by a factor of seven over leaf and stem in the cattle work ^{4Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study →}.

That variability is the practical point: growing location, season, plant part and species all move bufadienolide content severalfold, so no Kalanchoe material can be assumed equivalent to another.

Discovery & Synthesis

Bryophyllin B was described in 1989, in the Antitumor Agents series, as a novel potent cytotoxic bufadienolide from Bryophyllum pinnatum; its structure was settled by 2D-NMR and the difference nuclear-Overhauser method, and the paper discusses its formation from bryotoxin C by acid treatment ^{1Reference 1Yamagishi T et al. · 1989In vitroAntitumor agents, 110View study →}. It followed the previous year’s characterisation of bryophyllin A — bryotoxin C itself — as a cytotoxic bufadienolide orthoacetate ^{2Reference 2Yamagishi T et al. · 1988In vitroStructure and stereochemistry of bryophyllin-A, a novel potent cytotoxic bufadienolide orthoacetate from Bryophyllum pinnatum — in vitroView study →}. The relationship is chemically legible: bryophyllin A carries a strained orthoacetate, and acid opens it.

That acid sensitivity raises a question the literature has not answered — how much bryophyllin B is present in intact plant tissue as opposed to generated during extraction. It is a known hazard in this class: bufadienolide profiles in Kalanchoe juices are reported as pairs that co-elute or interconvert, such as bryophyllin A with bryotoxin C and bersaldegenin acetate with bryophyllin C ^{14Reference 14Hering A et al. · 2025In vitroBufadienolide Penetration Through the Skin Membrane and Antiaging Properties of Kalanchoe sppView study →}.

No total synthesis of bryophyllin B has been published, and there is no commercial source. It exists as an isolate in a small number of laboratories.

Patents: not yet researched.

Toxicity & Safety

Bryophyllin B carries a poisonous flag on class grounds, and the class grounds are strong.

Safety at a Glance

☠️ Poisonous

• A cardiac glycoside. Bufadienolides inhibit Na⁺/K⁺-ATPase as digoxin does; the therapeutic-to-toxic margin for this class is narrow even for the purified pharmaceutical members, and no margin has ever been established for this one ^{10Reference 10Sousa LQ et al. · 2017ReviewBufadienolides from amphibians: A promising source of anticancer prototypes for radical innovation, apoptosis triggering and Na(+)/K(+)-ATPase inhibition — reviewView study →}.
• Documented fatal poisoning in livestock. 41 incidents and 379 cattle in one Queensland series, with myocardial degeneration and necrosis; flowers are the most toxic part at an LD50 of 0.7 g dry matter/kg ^{4Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study →}.
• Fatal in people, in the form of related bufadienolide preparations. Four of six men died of dysrhythmias after ingesting a toad-venom product; the two survivors were treated with digoxin-specific Fab fragments ^{11Reference 11Brubacher JR et al. · 1996Case reportTreatment of toad venom poisoning with digoxin-specific Fab fragments — case reportView study →}.
• Cytotoxicity is not selectivity. The 1989 report is the only molecule-specific study, and pump inhibition affects every nucleated cell ^{1,10Reference 1Yamagishi T et al. · 1989In vitroAntitumor agents, 110View study →Reference 10Sousa LQ et al. · 2017ReviewBufadienolides from amphibians: A promising source of anticancer prototypes for radical innovation, apoptosis triggering and Na(+)/K(+)-ATPase inhibition — reviewView study →}.
• Species and plant part decide the exposure. Bufadienolide content varies severalfold between Kalanchoe species, growing regions, seasons and plant parts, and flowers are the hazard ^{4,5,6Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study →Reference 5McKenzie RA et al. · 1987The toxicity to cattle and bufadienolide content of six Bryophyllum species — animal studyView study →Reference 6Oufir M et al. · 2015Quantification of Bufadienolides in Bryophyllum pinnatum Leaves and Manufactured Products by UHPLC-ESIMS/MSView study →}.

Full Safety & Interactions Detail

Presentation of poisoning. Bufadienolide toxicity is cardiac glycoside toxicity. In cattle: anorexia, depression, ruminal atony, diarrhoea, heart-rate and rhythm abnormalities, dyspnoea and death, with myocardial degeneration and necrosis, cardiac and alimentary haemorrhage, and in severe cases pulmonary atelectasis and emphysema; raised plasma urea, creatinine and glucose with lowered chloride were measured experimentally ^{4Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study →}. In people, the documented bufadienolide cases presented with vomiting and bradycardia progressing to fatal dysrhythmia ^{11Reference 11Brubacher JR et al. · 1996Case reportTreatment of toad venom poisoning with digoxin-specific Fab fragments — case reportView study →}.

The digoxin assay cross-reacts, and that is clinically useful. Patients poisoned by bufadienolides showed positive apparent-digoxin levels ^{11Reference 11Brubacher JR et al. · 1996Case reportTreatment of toad venom poisoning with digoxin-specific Fab fragments — case reportView study →}, and bufadienolides in traditional Chinese medicines are detectable — with caveats — by digoxin immunoassays ^{11Reference 11Brubacher JR et al. · 1996Case reportTreatment of toad venom poisoning with digoxin-specific Fab fragments — case reportView study →}. Digoxin-specific Fab fragments were effective in the two treated survivors, which is the one piece of treatment evidence the class has ^{11Reference 11Brubacher JR et al. · 1996Case reportTreatment of toad venom poisoning with digoxin-specific Fab fragments — case reportView study →}.

Interactions, by class logic rather than by study. No interaction study exists for bryophyllin B. For cardiac glycosides generally, anything that lowers serum potassium — loop and thiazide diuretics, corticosteroids — increases toxicity at a given exposure, and concurrent digoxin or another cardiac glycoside is additive at the same pump. This is class reasoning applied to an untested molecule, not a measured interaction.

Reproductive note. A bufadienolide-enriched fraction of B. pinnatum inhibits human myometrial contractility in vitro, which is the mechanistic basis proposed for the plant’s use as an obstetric tocolytic ^{8Reference 8Santos S et al. · 2019In vitroA Bufadienolide-Enriched Fraction of Bryophyllum pinnatum Inhibits Human Myometrial Contractility In VitroView study →}. That is an effect on uterine tissue, established for a fraction and not for this molecule, and it is not a safety finding in either direction — no reproductive or developmental toxicity study of any isolated bryophyllin exists.

What is not known. There is no acute or repeat-dose toxicology, no genotoxicity assay and no pharmacokinetics for bryophyllin B in any species. The flag rests on the compound’s class, its measured cytotoxicity, and the veterinary and human record of bufadienolide poisoning.

Dosage

There is no dose. Bryophyllin B has no therapeutic use, no established safe exposure and no human administration of any kind. The figures below are the class figures that bear on exposure:

These are toxicology and content figures, not a personal recommendation, and none of them describes a safe intake.

References

1. Yamagishi T, Haruna M, Yan XZ, et al. (1989). Antitumor agents, 110. Bryophyllin B, a novel potent cytotoxic bufadienolide from Bryophyllum pinnatum — in vitro. J Nat Prod. https://pubmed.ncbi.nlm.nih.gov/2607348/
2. Yamagishi T, Yan XZ, Wu RY, et al. (1988). Structure and stereochemistry of bryophyllin-A, a novel potent cytotoxic bufadienolide orthoacetate from Bryophyllum pinnatum — in vitro. Chem Pharm Bull (Tokyo). https://pubmed.ncbi.nlm.nih.gov/3416378/
3. Supratman U, Fujita T, Akiyama K, et al. (2000). New insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata — in vivo insect assay. Biosci Biotechnol Biochem. https://pubmed.ncbi.nlm.nih.gov/10923811/
4. McKenzie RA, Dunster PJ (1986). Hearts and flowers: Bryophyllum poisoning of cattle — animal study. Aust Vet J. https://pubmed.ncbi.nlm.nih.gov/3778371/
5. McKenzie RA, Franke FP, Dunster PJ (1987). The toxicity to cattle and bufadienolide content of six Bryophyllum species — animal study. Aust Vet J. https://pubmed.ncbi.nlm.nih.gov/3439945/
6. Oufir M, Seiler C, Gerodetti M, et al. (2015). Quantification of Bufadienolides in Bryophyllum pinnatum Leaves and Manufactured Products by UHPLC-ESIMS/MS. Planta Med. https://pubmed.ncbi.nlm.nih.gov/26132852/
7. Fürer K, Simões-Wüst AP, von Mandach U, et al. (2016). Bryophyllum pinnatum and Related Species Used in Anthroposophic Medicine: Constituents, Pharmacological Activities, and Clinical Efficacy — review. Planta Med. https://pubmed.ncbi.nlm.nih.gov/27220081/
8. Santos S, Haslinger C, Klaic K, et al. (2019). A Bufadienolide-Enriched Fraction of Bryophyllum pinnatum Inhibits Human Myometrial Contractility In Vitro. Planta Med. https://pubmed.ncbi.nlm.nih.gov/30562827/
9. Fürer K, Eberli D, Betschart C, et al. (2015). Inhibition of porcine detrusor contractility by the flavonoid fraction of Bryophyllum pinnatum—a potential phytotherapeutic drug for the treatment of the overactive bladder syndrome — in vitro. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/25636885/
10. Sousa LQ, Machado KD, Oliveira SF, et al. (2017). Bufadienolides from amphibians: A promising source of anticancer prototypes for radical innovation, apoptosis triggering and Na(+)/K(+)-ATPase inhibition — review. Toxicon. https://pubmed.ncbi.nlm.nih.gov/28069354/
11. Brubacher JR, Ravikumar PR, Bania T, et al. (1996). Treatment of toad venom poisoning with digoxin-specific Fab fragments — case report. Chest. https://pubmed.ncbi.nlm.nih.gov/8915235/
12. Botha C (2016). Potential Health Risks Posed by Plant-Derived Cumulative Neurotoxic Bufadienolides in South Africa — review. Molecules. https://pubmed.ncbi.nlm.nih.gov/27102163/
13. Supratman U, Fujita T, Akiyama K, et al. (2001). Anti-tumor promoting activity of bufadienolides from Kalanchoe pinnata and K. daigremontiana x tubiflora — in vitro. Biosci Biotechnol Biochem. https://pubmed.ncbi.nlm.nih.gov/11388478/
14. Hering A, Cal K, Kowalczyk M, et al. (2025). Bufadienolide Penetration Through the Skin Membrane and Antiaging Properties of Kalanchoe spp. Juices in Dermal Applications — in vitro. Molecules. https://pubmed.ncbi.nlm.nih.gov/40005113/

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