Compound Monograph

Bryophyllin C

Terpenoids Cardiac Glycosides Natural (plant-derived)

Bryophyllin C is an insecticidal bufadienolide from Kalanchoe pinnata — a cardiac-glycoside-class steroid that kills silkworm larvae at 5 µg per gram of diet. It is the reduction analogue of bryophyllin A, it inhibits Na⁺/K⁺-ATPase as its class does, and the same class is the documented cause of fatal myocardial poisoning in grazing cattle.

Sources · 1

Where Does It Come From?

Bryophyllin C is a naturally occurring bufadienolide (cardiac glycoside-class steroid), found in Kalanchoe. It is flagged as poisonous.

Also found in
Kalanchoe Monograph coming soon

Concentration

Content by Source

Concentrations not reported. No percent-dry-weight or mg/g figures have been published for this compound in its source plants.

Bryophyllin C at a Glance

Bryophyllin C is a bufadienolide — a cardiac-glycoside-class steroid — first described in 2000 from the leaves of Kalanchoe pinnata (Bryophyllum pinnatum). It was not found by looking for a medicine. It came out of bioassay-guided fractionation for insecticidal activity, and it works: against third-instar silkworm larvae it has an LD50 of 5 µg per gram of diet, against 3 µg/g for its better-known relative bryophyllin A 3Reference 3Supratman U et al. · 2000AnimalNew insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata — in vivo insect assayView study →.

Structurally it is the reduction analogue of bryophyllin A, and its structure was settled partly by chemically transforming bryophyllin A into it 3Reference 3Supratman U et al. · 2000AnimalNew insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata — in vivo insect assayView study →. Pharmacologically it belongs to the same family as digoxin and digitoxin: bufadienolides inhibit the sodium–potassium ATPase, the pump that every animal cell uses to hold its ionic gradient 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 →.

That is why an insecticidal result and a cardiotoxic result are the same finding. The Bryophyllum bufadienolides are the documented cause of fatal myocardial poisoning in cattle — 41 recorded incidents affecting 379 animals in Queensland over 24 years 4Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study → — and human poisoning by bufadienolide preparations presents as, and cross-reacts with, digoxin toxicity 11Reference 11Brubacher JR et al. · 1996Case reportTreatment of toad venom poisoning with digoxin-specific Fab fragments — case reportView study →.

An Insect Poison and a Heart Poison Are the Same Molecule

The bufadienolides carry a C24 steroid nucleus with a six-membered α-pyrone at C17. They bind Na⁺/K⁺-ATPase in a manner structurally analogous to the digoxin– and ouabain–pump complexes; intracellular sodium rises, sodium–calcium exchange falters, calcium accumulates, and downstream the cell runs the intrinsic apoptotic programme — mitochondrial depolarisation, cytochrome-c release, caspase activation, PARP cleavage 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 →.

Insects have the same pump. So the dietary lethality in Bombyx mori 3Reference 3Supratman U et al. · 2000AnimalNew insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata — in vivo insect assayView study →, the cytotoxicity of the class in cultured cells 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 →, and the myocardial necrosis in grazing cattle 4Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study → are three readouts of one action, distinguished only by which organism was dosed. Bryophyllin C is not selectively an insecticide. It is a general Na⁺/K⁺-ATPase inhibitor that happened to be found in an insecticidal screen.

The screen that found it makes the point neatly: it isolated two insecticidal compounds from the leaf, and the other was bryophyllin A — the same compound described twelve years earlier as a potent cytotoxic bufadienolide orthoacetate 2,3Reference 2Yamagishi T et al. · 1988In vitroStructure and stereochemistry of bryophyllin-A, a novel potent cytotoxic bufadienolide orthoacetate from Bryophyllum pinnatum — in vitroView study →Reference 3Supratman U et al. · 2000AnimalNew insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata — in vivo insect assayView study →. One molecule, two literatures, one mechanism.

The class comparison holds in a third assay too. 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 — lacking the orthoacetate’s full arrangement — and bersaldegenin-3-acetate both weaker 13Reference 13Supratman U et al. · 2001In vitroAnti-tumor promoting activity of bufadienolides from Kalanchoe pinnata and K. daigremontiana x tubiflora — in vitroView study →. Across insecticidal potency, cytotoxicity and this assay, the ordering is the same and the structural feature that drives it is the same.

What It's Used For

Two primary papers name this molecule, both from the same group, and both are potency comparisons against bryophyllin A. The rest is class pharmacology and veterinary toxicology.

Insecticidal at a real potency.LD50 5 µg/g of diet against third-instar Bombyx mori larvae, from a bioassay-guided fractionation designed to find exactly this 3Reference 3Supratman U et al. · 2000AnimalNew insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata — in vivo insect assayView study →.
The mechanism is Na⁺/K⁺-ATPase inhibition, shared with digoxin and with the amphibian bufadienolides, and it accounts for the insecticidal, cytotoxic and cardiotoxic effects together 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 →.
Consistently the weaker sibling.In both assays where bryophyllin A and C were compared head to head — silkworm lethality and EBV early-antigen suppression — bryophyllin C came second 3,13Reference 3Supratman U et al. · 2000AnimalNew insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata — in vivo insect assayView study →Reference 13Supratman U et al. · 2001In vitroAnti-tumor promoting activity of bufadienolides from Kalanchoe pinnata and K. daigremontiana x tubiflora — in vitroView study →.
The class kills grazing cattle by damaging myocardium, at a median lethal dose of 0.7 g dry flower matter per kg liveweight 4Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study →.
Evidence by IndicationStrength of support · Beta

Mechanisms

Target / pathwayEffectRelevant to
Na⁺/K⁺-ATPaseinhibition, by a binding mode analogous to the digoxin– and ouabain–pump complexes
insecticidalcytotoxic and cardiotoxic activity alike
Intracellular Na⁺ / Ca²⁺ handlingsodium accumulation impairs Na⁺/Ca²⁺ exchange; calcium rises
arrhythmia and myocardial necrosis in poisoned animals
Mitochondria and the intrinsic apoptotic cascadedepolarisation, cytochrome-c release, caspase activation
the cell-culture readouts
Insect Na⁺/K⁺-ATPasethe same pump, in an organism small enough for a dietary dose to be lethal
the silkworm LD50
Human vs. rodent ATPase subunitsbufadienolides are markedly less active on murine cells than human
why rodent tolerance data understate human risk

The orthoacetate arrangement of bryophyllin A appears to be what makes it the more potent of the pair, consistently across three unrelated assays 3,13Reference 3Supratman U et al. · 2000AnimalNew insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata — in vivo insect assayView study →Reference 13Supratman U et al. · 2001In vitroAnti-tumor promoting activity of bufadienolides from Kalanchoe pinnata and K. daigremontiana x tubiflora — in vitroView study →.

Pharmacokinetics

None published, in any species. The one exposure-relevant measurement for this class in this plant is dermal: applied to a skin-barrier model, Kalanchoe juice bufadienolides — bryophyllin C among the compounds profiled — did not appear in the subcutaneous filtrate 14Reference 14Hering A et al. · 2025In vitroBufadienolide Penetration Through the Skin Membrane and Antiaging Properties of Kalanchoe sppView study →. That bears on topical cosmetic use and says nothing about ingestion.

Clinical Trials

None. The human 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 →.

CompletedPlannedTerminatedPreclinical
———Insect lethality; one cell-based tumour-promotion assay; class-level mechanism and veterinary toxicology

Last checked: September 2026.

Isolate vs. Plant Studies

The isolate work is two papers, both comparative. The plant work is much larger, and it makes a point that reframes both: in B. pinnatum the useful and the dangerous chemistry are physically separable, and the separation has been done. 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 bladder activity that the plant is being developed for is not the bufadienolides.

The obstetric use runs the other way: on human myometrial strips, a bufadienolide-enriched fraction was the most potent tocolytic tested, at 1 µg/mL against 150 µg/mL for the flavonoid fraction, without loss of 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 does contribute something. 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 deliberately given to a person.

Prevalence in Nature

Bryophyllin C is reported from the leaves of Kalanchoe pinnata (Bryophyllum pinnatum), a Madagascan succulent naturalised across the tropics and subtropics, and has been detected in the pressed juices of K. pinnata and K. daigremontiana in a profiling study — though co-eluting with bersaldegenin acetate, which is a recurring analytical problem in this class 14Reference 14Hering A et al. · 2025In vitroBufadienolide Penetration Through the Skin Membrane and Antiaging Properties of Kalanchoe sppView study →. Its distribution across the genus has not been surveyed.

The class picture is better quantified and highly variable. Total bufadienolide content of B. pinnatum leaf runs 16.3–40.5 mg/100 g dry weight in Brazilian-grown plants against 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, and content 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 →. Which bufadienolide predominates changes with species: bersaldegenin-1,3,5-orthoacetate leads in 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 are the most toxic part of the plant by a factor of seven over leaf and stem 4Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study →.

Growing location, season, plant part and species each move bufadienolide content severalfold. No Kalanchoe material can be assumed equivalent to another, which is the practical reason species identification matters more than quantity here.

Discovery & Synthesis

Bryophyllin C was described in 2000. Two insecticidal bufadienolides were isolated from a methanol extract of K. pinnata leaves by bioassay-guided fractionation; the first proved to be the known bryophyllin A (bryotoxin C), and the second was new. Its structure was determined by spectroscopic methods and by chemically transforming bryophyllin A into it — the relationship that makes it the reduction analogue 3Reference 3Supratman U et al. · 2000AnimalNew insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata — in vivo insect assayView study →. A follow-up from the same group placed it in a five-compound bufadienolide comparison the following year 13Reference 13Supratman U et al. · 2001In vitroAnti-tumor promoting activity of bufadienolides from Kalanchoe pinnata and K. daigremontiana x tubiflora — in vitroView study →.

No total synthesis has been published, and there is no commercial supply. The compound exists as an isolate, and its analytical behaviour is awkward: bufadienolide pairs in Kalanchoe juice co-elute and interconvert, with bersaldegenin acetate and bryophyllin C among the pairs reported together rather than separately 14Reference 14Hering A et al. · 2025In vitroBufadienolide Penetration Through the Skin Membrane and Antiaging Properties of Kalanchoe sppView study →.

Patents: not yet researched.

Toxicity & Safety

Bryophyllin C carries a poisonous flag on class grounds, reinforced by its own measured lethality in an animal.

Safety at a Glance
Poisonous
  • A cardiac glycoside. Bufadienolides inhibit Na⁺/K⁺-ATPase as digoxin does; the therapeutic-to-toxic margin is narrow even for the purified pharmaceutical members of this target class, and no margin has been established for this compound 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 →.
  • Lethal to a test animal at microgram doses. LD50 5 µg per gram of diet in silkworm larvae — the assay it was discovered in 3Reference 3Supratman U et al. · 2000AnimalNew insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata — in vivo insect assayView study →.
  • Documented fatal poisoning in livestock and in people. 41 Bryophyllum incidents and 379 cattle in one Queensland series with myocardial necrosis 4Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study →; four deaths of six in a human bufadienolide-preparation series 11Reference 11Brubacher JR et al. · 1996Case reportTreatment of toad venom poisoning with digoxin-specific Fab fragments — case reportView 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 →.
  • No mammalian toxicology of its own. No acute or repeat-dose study, no genotoxicity, no reproductive data and no pharmacokinetics for the isolated molecule.
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 pulmonary atelectasis and emphysema in severe dyspnoea; plasma urea, creatinine and glucose rose and chloride fell in the experimental animals 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 →.

A slower form exists. In South Africa, Cotyledon, Tylecodon and Kalanchoe species cause “krimpsiekte”, a chronic paretic and paralytic condition from cumulative neurotoxic bufadienolides — cotyledoside, the tyledosides, orbicusides and lanceotoxins, a different structural subgroup from the bryophyllins. Consumption of edible tissues from affected animals is a documented risk to people 12Reference 12Botha C · 2016ReviewPotential Health Risks Posed by Plant-Derived Cumulative Neurotoxic Bufadienolides in South Africa — reviewView study →.

Treatment evidence. Bufadienolides cross-react with digoxin immunoassays, so apparent-digoxin levels are positive in poisoning 11Reference 11Brubacher JR et al. · 1996Case reportTreatment of toad venom poisoning with digoxin-specific Fab fragments — case reportView study →, and digoxin-specific Fab fragments were effective in the two treated survivors of the toad-venom series — the one piece of treatment evidence this 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 C. For cardiac glycosides generally, anything that lowers serum potassium — loop and thiazide diuretics, corticosteroids — raises toxicity at a given exposure, and any concurrent cardiac glycoside is additive at the same pump. That 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 proposed mechanistic basis for the plant’s obstetric tocolytic use 8Reference 8Santos S et al. · 2019In vitroA Bufadienolide-Enriched Fraction of Bryophyllum pinnatum Inhibits Human Myometrial Contractility In VitroView study →. That is a fraction-level finding on isolated tissue and not a property established for this molecule; no reproductive or developmental toxicity study of any isolated bryophyllin exists.

What the grading rests on. It rests on the compound’s class, its measured insect lethality, and the veterinary and human record of bufadienolide poisoning — not on a toxicology package for the molecule, which does not exist.

Dosage

There is no dose. Bryophyllin C has no therapeutic use and no human administration of any kind. The figures on record:

SettingFormFigure
Silkworm larval lethalityCompound in dietLD50 5 µg/g (bryophyllin A 3 µg/g) 3Reference 3Supratman U et al. · 2000AnimalNew insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata — in vivo insect assayView study →
EBV early-antigen inhibitionIn-vitro cultureLess active than bryophyllin A at IC50 0.4 µM 13Reference 13Supratman U et al. · 2001In vitroAnti-tumor promoting activity of bufadienolides from Kalanchoe pinnata and K. daigremontiana x tubiflora — in vitroView study →
Cattle lethality, B. tubiflorum flowersGrazed plant materialLD50 0.7 g dry matter/kg liveweight 4Reference 4McKenzie RA · 1986Hearts and flowers: Bryophyllum poisoning of cattle — animal studyView study →
Total leaf bufadienolides, B. pinnatumDried leaf3.8–40.5 mg/100 g, by growing location 6Reference 6Oufir M et al. · 2015Quantification of Bufadienolides in Bryophyllum pinnatum Leaves and Manufactured Products by UHPLC-ESIMS/MSView study →
Total bufadienolides, press juiceStandardised press juice0.09–1.16 mg/100 mL 6Reference 6Oufir M et al. · 2015Quantification of Bufadienolides in Bryophyllum pinnatum Leaves and Manufactured Products by UHPLC-ESIMS/MSView study →

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/