# Pawpaw (Asimina triloba) *Papaw, American custard-apple; *asiminier* of the French colonists; *Asimina triloba* of Dunal, *Annona triloba* of Linnaeus, *Uvaria triloba*, *Porcelia triloba*; not the papaya, *Carica papaya*, which has borrowed the name* **Known today as.** *Asimina triloba*, the one temperate tree of the custard-apple family: ten to thirty feet high, with long thin leaves, dull purple flowers that open with or before the leaves, and oblong pulpy fruits like short bananas, native to the central belt of the United States from western New York to the Mississippi and southward, along streams where the soil is rich and the frosts come late. Kind: Plant Toxic: yes > **Caution.** The ripe pulp has been eaten in the Ohio valley for as long as there are records of it, and the seeds and bark were known to be emetic and bitter. The acetogenins measured in the pulp in 2012 are toxic to nerve cells in culture, and their risk in long use has not been studied; twig extracts sold as cancer remedies carry the same compounds in greater strength. ## What was it used for? A fruit more than a medicine. Rafinesque found the pulp, sweet, luscious, and yellow like a custard when ripe after frost, to be “sedative, laxative and healthy,” and a clear wine made of it useful for the mouth-sores of children; the Indians, he says, made strong ropes of the bark. Millspaugh, who thought the former medical uses of little or no importance, records that a tincture of the seed proves emetic and that the bitter bark was taken for a tonic; the fruit, greatly prized by the aborigines, was in his day occasionally sold in city markets, and “only fit to eat after having been touched by frost,” when it turns from yellowish-green to black and becomes inside of the colour and consistence of custard. ## What does modern science say? The pawpaw holds annonaceous acetogenins, the compounds of its tropical relatives, in twigs, unripe fruit, seeds, roots, and bark, and, a 2009 study found, in the ripe pulp too, where asimicin, bullatacin, and bullatalicin were identified and the pulp extract was as active in a brine-shrimp assay as the twig extract. In 2012 annonacin, a mitochondrial complex I inhibitor, was measured in the fruit pulp at about 0.07 milligrams a gram, and both it and the crude extract killed half of cultured rat cortical neurons in two days; the authors called for studies of the risk of chronic exposure, since related compounds in soursop and its leaf tea have been linked to atypical Parkinsonism. Twig extracts are sold as an anticancer alternative medicine; in cells they block the hypoxia signal that drives tumour blood supply, by the same inhibition of complex I. ## Pharmacognosy and toxicology - **annonaceous acetogenins**: asimicin, bullatacin, and bullatalicin identified in the ripe pulp; in twigs, unripe fruit, seeds, roots, and bark besides - **annonacin**: a complex I inhibitor measured at about 0.07 milligrams a gram of fruit pulp, toxic to cultured cortical neurons **Mechanism.** The acetogenins inhibit mitochondrial complex I; in tumour cells this blocks the hypoxia-inducible factor HIF-1 and the VEGF it drives, which is the proposed anticancer mechanism of the twig-extract products, and in cultured neurons the same inhibition kills, which is the proposed hazard. **Dose.** A fruit, eaten ripe; Millspaugh’s tincture of the ripe seeds was an emetic. No dose of the acetogenins is established for people. **Standing.** A regional fruit crop and a cancer alternative medicine, with the same compounds behind both; the question of long-term neurotoxicity from the fruit was raised in 2012 and has not been answered in any study read here. ## What lore surrounds it? A tree of two names and two smells: the custard that gives it its common name is what the frost makes of a fruit that, green, smells to Rafinesque like the thorn-apple, and the pawpaw and the papaya have been confused in every herbal since the French of Louisiana called it *asiminier*. Millspaugh, who could find no analysis of it, hoped that a preparation of the seeds, bark, and green fruit might prove of use; a century later the chemists found the whole tree, pulp included, full of the acetogenins of its tropical cousins. ## What did the older authorities say? **C. S. Rafinesque.** “Fruit with a bad smell, but when ripe after frost, the pulp is sweet, luscious, yellow, similar to Custards. It is sedative, laxative and healthy. A wine is made of it, quite clear and good, useful for aphthas of children. The skin of the fruit and the seeds are fetid, smell similar to Datura.” All these shrubs, he adds, deserve cultivation. **Charles F. Millspaugh.** A native especially of the Ohio valley, flowering from March to May, grown in a protected place in Central Park but not hardy north of Cincinnati. The ripe fruit is “soft, sweet, and insipid, having a taste somewhat between that of the May-apple and the banana”; green, it has a very unpleasant odour. “The chemical properties and physiological action have never been—to my knowledge—determined.” His tincture is of the ripe seeds. **Mrs. M. Grieve.** Her Papaw is the tropical *Carica papaya*, the source of papain, and she warns that it “must not be confounded with the custard apple, which is often called Papaw and botanically known as *Uvaria triloba*”: this tree. ## Sources - Millspaugh, C. F. (1887). *American Medicinal Plants*, vol. 1, no. 13, “Asimina triloba,” and Plate 13. Internet Archive, americanmedicina01mill_0. - Rafinesque, C. S. (1830). *Medical Flora, or Manual of the Medical Botany of the United States of North America*, vol. 2, “Asimina,” p. 194. Internet Archive, b21468710_0002. - Grieve, M. *A Modern Herbal*, “Papaw.” As published on botanical.com. - Potts, L. F., Luzzio, F. A., Smith, S. C., Hetman, M., Champy, P., & Litvan, I. (2012). Annonacin in *Asimina triloba* fruit: implication for neurotoxicity. *Neurotoxicology* 33: 53–58. doi:10.1016/j.neuro.2011.10.009 - Pomper, K. W., Lowe, J. D., Crabtree, S. B., & Keller, W. (2009). Identification of annonaceous acetogenins in the ripe fruit of the North American pawpaw (*Asimina triloba*). *Journal of Agricultural and Food Chemistry* 57: 8339–8343. doi:10.1021/jf9018239 - Coothankandaswamy, V., et al. (2010). The alternative medicine pawpaw and its acetogenin constituents suppress tumor angiogenesis via the HIF-1/VEGF pathway. *Journal of Natural Products* 73: 956–961. doi:10.1021/np100228d --- *Pawpaw.* In *Materia Medica*, edited by B. C. P. Statema. Version 1, revised 2026-10-04. The Thinking Press. https://thethinkingpress.org/materia-medica/pawpaw Historical description, not medical advice.