# Antiarigenin

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**Antiarigenin** is a highly toxic [cardenolide](/source/Cardenolide) [aglycone](/source/Aglycone) found in the [latex](/source/Latex) of *[Antiaris toxicaria](/source/Antiaris_toxicaria)* ([upas tree](/source/Upas_tree)).[1] As the [steroid](/source/Steroid) core of α-[antiarin](/source/Antiarin) and β-antiarin [glycosides](/source/Glycoside), it has been used for centuries by [indigenous peoples](/source/Indigenous_peoples) of [Southeast Asia](/source/Southeast_Asia) in [blowdart](/source/Blowgun) [arrow poisons](/source/Arrow_poison).[2] It functions as a potent [Na+/K+-ATPase](/source/Na%2B/K%2B-ATPase) inhibitor and has shown potential to induce [apoptosis](/source/Apoptosis) in [chemotherapy](/source/Chemotherapy)-resistant [cancer](/source/Cancer) cells through [orphan nuclear receptor](/source/Orphan_nuclear_receptor) [Nur77](/source/Nur77) modulation.[3]

## Natural occurrence

Antiarigenin serves as a [chemotaxonomic](/source/Chemotaxonomy) marker for the genus *[Antiaris](/source/Antiaris)* ([Moraceae](/source/Moraceae)).[4] *A. toxicaria* is a large [deciduous tree](/source/Deciduous_tree) native to [tropical](/source/Tropical) regions from [West Africa](/source/West_Africa) through the [Indian subcontinent](/source/Indian_subcontinent) and [Southern China](/source/Southern_China) to [Indonesia](/source/Indonesia) and [Northern Australia](/source/Northern_Australia).[4] The tree's milky latex contains high concentrations of cardenolides, particularly in the [bark](/source/Bark_(botany)), with lower amounts in [seeds](/source/Seed) and [leaves](/source/Leaf).[5]

Antiarigenin is rarely stored freely; [glycosyltransferase](/source/Glycosyltransferase) [enzymes](/source/Enzymes) attach [sugars](/source/Sugar), usually [L-rhamnose](/source/Rhamnose) or D-antiarose, to the C-3 [hydroxyl](/source/Hydroxyl) group, forming the parent glycosides.[1] [Biosynthesis](/source/Biosynthesis) proceeds via the [pregnane](/source/Pregnane) pathway, with [phytosterol](/source/Phytosterol) precursors undergoing [side-chain](/source/Side_chain) [cleavage](/source/Cleavage_(chemistry)), [stereoselective](/source/Stereochemistry) [reduction](/source/Redox), specific [hydroxylations](/source/Hydroxylation), and [oxidation](/source/Oxidation) of the C-19 [methyl group](/source/Methyl_group) to an [aldehyde](/source/Aldehyde).[6]

## Chemical structure

Antiarigenin has a tetracyclic [gonane](/source/Steroid) nucleus with a *[cis](/source/Cis-trans_isomerism)*–*[trans](/source/Cis-trans_isomerism)*–*cis* ring fusion pattern.[1] The A/B [ring](/source/Cyclic_compound) junction is *cis*-fused (5β-H), creating a molecular "kink" essential for binding to the [cardiac glycoside](/source/Cardiac_glycoside) receptor site on Na+/K+-ATPase.[7] Key [functional groups](/source/Functional_groups) include four [hydroxyl](/source/Hydroxyl) groups (C-3β, C-5β, C-12β, C-14β), a C-19 aldehyde (distinguishing it from [digitoxigenin](/source/Digitoxigenin)), and a [butenolide](/source/Butenolide) (unsaturated γ-[lactone](/source/Lactone)) ring at C-17β.[1][5] This places it in the [strophanthidin](/source/Strophanthidin) class of cardenolides.[1]

The structure is confirmed by [NMR](/source/Nuclear_magnetic_resonance_spectroscopy) and [X-ray crystallography](/source/X-ray_crystallography). The 1H [NMR](/source/NMR_spectroscopy) shows a characteristic aldehyde [proton](/source/Proton) at δH 9.8–10.5 [ppm](/source/Parts_per_million), while 13C NMR reveals the aldehyde [carbon](/source/Carbon) at ~208 ppm and lactone [carbonyl](/source/Carbonyl) at ~175 ppm.[1]

## Mechanism of action

Antiarigenin binds the [Na+/K+-ATPase](/source/Na%2B/K%2B-ATPase) (sodium pump), stabilizing it in the [phosphorylated](/source/Phosphorylation) E2-P [conformation](/source/Protein_structure) and blocking [ion exchange](/source/Ion_exchange).[8] In [cardiac myocytes](/source/Cardiac_muscle), this raises [intracellular](/source/Intracellular) [calcium](/source/Calcium), producing a positive [inotropic](/source/Inotropic) effect at therapeutic doses or [cardiac arrest](/source/Cardiac_arrest) at toxic doses.[5]

Antiarigenin shows [isoform](/source/Protein_isoform) selectivity among Na+/K+-ATPase α-subunits, preferentially targeting the α3 isoform enriched in [neurons](/source/Neurons) and [cardiac conduction tissue](/source/Cardiac_conduction_system).[9] This may explain prominent [neurotoxicity](/source/Neurotoxicity) in *Antiaris* poisoning.

A second mechanism involves [Nur77](/source/Nur77) modulation. Antiarigenin triggers [nuclear export](/source/Nuclear_export) of Nur77, which then binds [Bcl-2](/source/Bcl-2) at the [mitochondrial](/source/Mitochondrion) membrane, converting it from an anti-apoptotic to a pro-apoptotic protein.[3] This leads to [cytochrome c](/source/Cytochrome_c) release and [caspase](/source/Caspase) activation, effective even in Bcl-2-overexpressing chemoresistant [cancer cells](/source/Cancer_cells).[3]

## Ethnobotany

Indigenous groups in Southeast Asia, notably the [Dayak](/source/Dayak_people) of [Borneo](/source/Borneo), have used *A. toxicaria* latex in blowdart poisons (*ipoh*, *tajum*) for [hunting](/source/Hunting) and [warfare](/source/Warfare).[2] Preparation required careful [dehydration](/source/Dehydration) to concentrate cardenolides without [hydrolyzing](/source/Hydrolysis) heat-labile [glycosidic bonds](/source/Glycosidic_bond).[4]

*Antiaris* latex was typically combined with *[Strychnos](/source/Strychnos)* extracts containing [strychnine](/source/Strychnine) and [brucine](/source/Brucine).[10] This [synergy](/source/Drug_synergy) ensured rapid immobilization: antiarigenin caused cardiotoxicity while strychnine, a [glycine receptor](/source/Glycine_receptor) [antagonist](/source/Receptor_antagonist), induced tetanic [convulsions](/source/Convulsions).[10]

## See also

- [Cardiac glycoside](/source/Cardiac_glycoside)
- [Cardenolide](/source/Cardenolide)
- [Digitalis](/source/Digitalis)
- [Strophanthin](/source/Strophanthin)
- [Ouabain](/source/Ouabain)
- [Antiaris toxicaria](/source/Antiaris_toxicaria)

## References

1. Carter, C.A.; Forsberg, L.S.; Xu, J.; Matainaho, T.; Kikuchi, H.; Clardy, J. (2013). "Antiproliferative Cardiac Glycosides from the Latex of *Antiaris toxicaria*". *J. Nat. Prod.*. **76** (10): 1838–1843. [doi:10.1021/np4005147](https://doi.org/10.1021/np4005147). [PMID 24093516](https://pubmed.ncbi.nlm.nih.gov/24093516)

1. Quisumbing, E. (1978). ["Blowpipe dart poison in Borneo and the secret of its production: the latex of *Antiaris toxicaria*"](https://nomadicpixel.com/wp-content/uploads/2015/08/Blowpipe-Dart-Poison-in-Borneo.pdf). Retrieved 12 February 2026.

1. Lin, B.; Kolluri, S.K.; Lin, F. (2018). "Induction of apoptosis and suppression of tumor growth by Nur77-derived Bcl-2 converting peptide in chemoresistant lung cancer cells". *Oncotarget*. **9** (40): 26072–26085. [PMC 5995251](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995251). [PMID 29899852](https://pubmed.ncbi.nlm.nih.gov/29899852)

1. ["*Antiaris toxicaria*"](https://prosea.prota4u.org/view.aspx?id=159). PROSEA – Plant Resources of South East Asia. Retrieved 12 February 2026.

1. Dai, H.F.; Gan, Y.J.; Que, D.M.; Wu, J.; Wen, Z.C.; Mei, W.L. (2010). "Cardiac Glycosides from *Antiaris toxicaria* with Potent Cardiotonic Activity". *Planta Med*. **76** (14): 1905–1907. [doi:10.1055/s-0030-1250036](https://doi.org/10.1055/s-0030-1250036). [PMC 2917517](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917517). [PMID 20533172](https://pubmed.ncbi.nlm.nih.gov/20533172)

1. Li, S.; Chen, J.; Zhang, Y. (2025). "A high-quality chromosome-level genome assembly of *Antiaris toxicaria*". *Sci Data*. **12**: 241. [doi:10.1038/s41597-025-03682-9](https://doi.org/10.1038/s41597-025-03682-9). [PMC 11934813](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934813). [PMID 38589421](https://pubmed.ncbi.nlm.nih.gov/38589421)

1. Hložek, T. & Kuchař, M. (2021). "Structural Insights into the Interactions of Digoxin and Na+/K+-ATPase". *Molecules*. **26** (12): 3672. [doi:10.3390/molecules26123672](https://doi.org/10.3390/molecules26123672). [PMC 8234910](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234910)

1. Laursen, M.; Gregersen, J.L.; Yatime, L. (2015). "Structures and characterization of digoxin- and bufalin-bound Na+,K+-ATPase". *Proc Natl Acad Sci USA*. **112** (6): 1755–1760. [doi:10.1073/pnas.1422997112](https://doi.org/10.1073/pnas.1422997112). [PMC 4330780](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330780)

1. Katz, A.; Lifshitz, Y.; Bab-Dinitz, E. (2016). "Isoform specificity of cardiac glycosides binding to human Na+,K+-ATPase". *Sci Rep*. **6**. [doi:10.1038/srep29759](https://doi.org/10.1038/srep29759). [PMC 4948948](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948948)

1. ["*Antiaris toxicaria* (PROSEA)"](https://plantuse.plantnet.org/en/Antiaris_toxicaria_(PROSEA)). Pl@ntUse. Retrieved 12 February 2026.

## External links

- [PubChem entry for Antiarigenin](https://pubchem.ncbi.nlm.nih.gov/compound/49799517)

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Adapted from the Wikipedia article [Antiarigenin](https://en.wikipedia.org/wiki/Antiarigenin) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Antiarigenin?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.