Paw paw

Paw Paw (Asimina triloba): A Comprehensive Reference

1. Identity and Botanical Classification

Scientific name: Asimina triloba (L.) Dunal. Family: Annonaceae (the custard apple family). Asimina triloba (L.) Dunal is commonly known as pawpaw, custard apple, Indiana banana, Kentucky banana, and poor man's banana.

Asimina triloba, commonly known as pawpaw, is native to North America and has edible bean-shaped fruits. It should not be confused with graviola, also known as Brazilian pawpaw, or with papaya, another fruit with a similar texture and appearance. Unlike the tropical papaya (often called pawpaw in other regions), this North American species contains unique acetogenins — bioactive compounds with potent effects on cellular metabolism, energy regulation, and abnormal cell growth control.

From Florida to Texas, north to New York, and west to Michigan, Illinois, Iowa, and Nebraska, paw paws are native to 26 states and grow as understory trees in hardwood forests near streams and rivers. In the wild, the trees grow to 15 to 30 feet and sucker, creating colonies.

The paw paw is a small tree native to eastern North America; its edible fruits (sometimes referred to as "Indiana Bananas") have nurtured mankind for centuries. The North American pawpaw (Asimina triloba L.) fruit is an underutilized specialty crop native to North America. Due to the short shelf life of the fruit, it has remained underutilized and uncommercialized.

Common Preparations and Commercial Forms

Paw paw extract is derived from the twigs and bark of the North American paw paw tree (Asimina triloba), a member of the custard apple family (Annonaceae). The small twigs (0–0.5 cm diameter) yield the most potent extract (LC50 = 0.04 ppm); the stem wood and leaves yield the poorest activities. The unripe fruits, seeds, root wood, root bark, and stem bark are notably potent and generally yield more than 2% of their dry weight as the standardized extract.

Practical applications of Asimina triloba extracts include a shampoo effective in the treatment of head lice infestation, a pesticidal spray, and an ointment for treatment of herpes (HSV-1) and other skin diseases. The extract in capsule form is used as a natural anthelmintic.

If someone is considering using pawpaw as a treatment, it is not only important to ensure that the product is from the Asimina triloba species of pawpaw, but also that the product is standardized — in other words, the manufacturer uses an extraction process for the acetogenins and ensures that a guaranteed set amount of acetogenins is actually in the product.

2. Traditional and Historical Use

Indigenous and Pre-Colonial Use

Pawpaw seeds and other remnants have been found at archaeological sites of the earliest Native Americans, in large, concentrated amounts, suggesting seasonal feasts of the fruit. The Cherokee, Shawnee, Iroquois, Miami, and other nations utilized the pawpaw in their traditional diets, incorporating it into a variety of dishes and preserving it for the winter months.

Beyond its culinary significance, the pawpaw held medicinal properties that were valued by Native American healers and medicine men. The fruit was used to treat a range of ailments, including skin conditions, digestive issues, and even as a general tonic for overall health. The Cherokee, for example, used pawpaw leaves and bark in medicinal preparations to soothe skin irritations and promote healing.

Native Americans commonly used pawpaw fruit as a nutrient-rich food source and applied poultices made from the bark and leaves to treat wounds, ulcers, and other skin ailments. The seeds and leaves, containing unique bioactive compounds, were sometimes prepared as teas or topical treatments to address parasitic infections and promote overall wellbeing.

The tough, fibrous inner bark of the pawpaw has traditionally been used by Native Americans and settlers in the Midwest for making ropes, fishing nets, and mats, and for stringing fish.

Due to the presence of acetogenins, the leaves, twigs, and bark of pawpaw trees can be used to make an organic insecticide.

Colonial and Early American Use

Jamestown colonists wrote about them in the 1600s and John Lawson, an Englishman, described them in his travels in the Carolinas in the 1700s. European settlers quickly adopted the paw paw for both its fruit and medicinal properties. Early American herbalists used infusions of the bark and leaves to treat fevers, infections, and worms. In Appalachian folk medicine, paw paw bark was occasionally used for intestinal parasites and as a digestive bitter.

During the Civil War, soldiers as well as African American slaves collected the fruit in the wild to supplement their meager diets.

In homeopathy, American pawpaw is used for treating fever, vomiting, and pain and swelling (inflammation) of the mouth and throat.

Modern Commercial Interest

Interest in paw paw's therapeutic potential surged in the 1990s and 2000s when researchers began isolating and testing acetogenins for their anticancer activity. This led to the development of commercial paw paw extract supplements, particularly marketed for immune support and as a natural adjunct to chemotherapy.

3. Key Constituents and Active Compounds

Annonaceous Acetogenins

The annonaceous acetogenins are derivatives of long-chain (C32 or C34) fatty acids. They are potent inhibitors of mitochondrial (complex I) as well as cytoplasmic (anaerobic) production of adenosine triphosphate (ATP) and the related nucleotides.

Extracts of paw paw (Asimina triloba, Annonaceae) are among the most potent of the 3,500 species of higher plants screened for bioactive compounds at Purdue University. Activity-directed fractionation of the paw paw extracts, using the brine shrimp lethality bioassay, led to the isolation and molecular characterization of over 50 unique annonaceous acetogenins. Fractionation of extracts from related species resulted in the identification of over 150 additional acetogenins.

Key individually identified acetogenins from A. triloba include annonacin, annonacin A, 10-hydroxyglaucanetin, squamocin, asimicin, asitrocin, asitrilobins A–D, asimilobin, and gigantetrocinone. Only a few alkaloids have been reported from this plant, including coreximine, asimilobine, isocorydine, squamolone, anolobine, liriodenine, norushinsunine, and squamolone.

Phenolic Compounds and Flavonoids

The fruit contains phenolic compounds, annonaceous acetogenins, alkaloids, carotenoids, and phytosterols. Analysis of 17 phenolic compounds in pawpaw extracts revealed that epigallocatechin, epicatechin, and p-coumaric acid were the major compounds, and the amounts of all components significantly decreased with ripening. A study of polyphenolic compounds in 10 varieties of pawpaw pulp reported that the predominant substances were three phenolic acids (protocatechuic acid hexoside, p-coumaroyl hexoside, and 5-O-p-coumaroylquinic acid) and three flavonols (epicatechin, B-type procyanidin dimers, and trimers).

Alkaloids

The root, bark, seed, and fruit pulp contain alkaloids, including asiminine, analobine, and acimilobine, which have potential therapeutic properties. A 2021 in vitro study published in the South African Journal of Botany assessed the cytotoxicity and neurotoxicity of alkaloid constituents derived from Asimina triloba twigs, confirming their biological activity.

Mechanistic Overview: How Acetogenins Act

At the molecular level, acetogenins are potent inhibitors of mitochondrial electron transport chain (ETC) complex I. The inhibition of mitochondrial respiration and subsequent ATP production may account for the broad biological activities exhibited by acetogenins and pawpaw extracts, ranging from anticancer, antimalarial, antiviral, antimicrobial, antiparasitic, to pesticidal activities.

Pawpaw extract and acetogenins inhibited HIF-1 activation by blocking the hypoxic induction of nuclear HIF-1α protein. The inhibition of HIF-1 activation was associated with the suppression of mitochondrial respiration at complex I.

4. Scientific Evidence by Area of Use

4.1 Anticancer Activity

In Vitro (Cell Culture) Evidence

In lab studies, the extract killed cancer cells resistant to commonly used chemotherapy drugs such as adriamycin. It also appeared to be more toxic to cancer cells than to normal cells. However, studies on these effects have not been conducted in humans.

Products containing twig extracts of pawpaw (Asimina triloba, Annonaceae) are widely consumed anticancer alternative medicines. Pawpaw crude extract and purified acetogenins inhibited hypoxia-inducible factor-1 (HIF-1)-mediated hypoxic signaling pathways in tumor cells. In T47D cells, pawpaw CE and the acetogenins 10-hydroxyglaucanetin, annonacin, and annonacin A inhibited hypoxia-induced HIF-1 activation with IC50 values of 0.02 μg/mL, 12 nM, 13 nM, and 31 nM, respectively. This inhibition correlates with the suppression of the hypoxic induction of HIF-1 target genes VEGF and GLUT-1.

In one study, the growth-inhibitory effects of pawpaw (Asimina triloba [L.] Dunal) extracts were tested against gastric (AGS) and cervical (HeLa) cancer cells, and the inhibitory effects against inflammatory factors (NO, TNF-α, IL-6, iNOS, and COX-2) were investigated. Pawpaw extracts from unripe fruit, rich in acetogenins, produced induction of apoptosis and had a cytotoxic effect on AGS tumoral gastric cells (IC50 82.01 µg/L) and HeLa cells (cervical cancer) (IC50 97.73 µg/mL).

Antiangiogenic Activity

Annonacin was submitted to the rat aortic ring bioassay for evaluation of antiangiogenic activity and was found to inhibit microvessel growth (IC50 value of 3 μM). Both the extract and the purified acetogenins blocked the angiogenesis-stimulating activity of hypoxic T47D cells in vitro. Thus, the inhibition of HIF-1 activation and hypoxic tumor angiogenesis constitutes a novel mechanism of action for these anticancer alternative medicines.

Animal Studies

Test tube studies suggest pawpaw may have activity against cancer cells, but experiments in mice produced conflicting results.

Human/Clinical Evidence

Cancer treatment: test tube studies suggest pawpaw may have activity against cancer cells, but experiments in mice produced conflicting results. There are no published clinical studies in humans that test safety or effectiveness of pawpaw as a cancer treatment. Although antiangiogenic, cytotoxic, antimicrobial, antioxidant, and pesticidal activities have been observed in vitro and in animal studies, published clinical trials are lacking to support its use for any indication.

Evidence strength summary: Preclinical (in vitro and limited animal) only. No published peer-reviewed human trials are available. Evidence for anticancer use is preliminary and cannot be extrapolated to clinical efficacy.

4.2 Pediculicidal Use (Head Lice Treatment)

Extracts of pawpaw twigs and leaves have been used in anti-lice shampoos and as pesticides. Early research suggests that applying a shampoo that contains American pawpaw, thymol, and tea tree oil to the head up to three times over 16 days can eliminate lice in adults and children.

A study published in Phytomedicine (2002) by McCage et al. evaluated the pawpaw herbal shampoo formulation: a 2002 study out of Spanish Fork, Utah evaluated the effects of an herbal shampoo containing pawpaw extract on lice and nits. According to the study, the shampoo was 100 percent effective at removing lice and nits in 16 people when applied topically.

Evidence strength summary: One small clinical study (n=16) using a multi-ingredient shampoo (pawpaw combined with thymol and tea tree oil), reported 100% efficacy. Because the formulation contained multiple active ingredients, the specific contribution of pawpaw extract alone cannot be isolated. Evidence is very limited but represents the most direct human-use data available.

4.3 Anti-Inflammatory Activity

The inhibitory effects of pawpaw extracts against inflammatory factors (NO, TNF-α, IL-6, iNOS, and COX-2) were investigated in vitro. Due to the high content of phenolic compounds, the twig, root, and unripe fruit extracts of pawpaw reduced the activity of inflammatory agents (NO, TNF-α, IL-6, and iNOS); at concentrations of 50 µg/mL, they produced 50% inhibition of TNF-α.

Evidence strength: In vitro only. No human studies.

4.4 Antioxidant Activity

The phenolic components, antioxidant, and antimicrobial activities of ripe and unripe pawpaw fruit were analyzed using five different solvents. The total phenolic content and total flavonoid content were the highest in the 95% ethanol and 80% ethanol extracts of the unripe fruit, respectively. In all antioxidant assays, the 95% ethanol extract of the unripe fruit showed the highest antioxidant activity (EC50 0.22 to 0.93 mg/mL).

These results showed that the unripe fruit of pawpaw has abundant phenolic compounds and superior antioxidant activity.

Evidence strength: In vitro only. No human intervention studies.

4.5 Antimicrobial Activity

The pawpaw extracts were more sensitive against Corynebacterium xerosis and Clostridium perfringens. The 95% ethanol extract of the ripe fruit showed a strong inhibitory effect against various microorganisms.

Evidence strength: In vitro (laboratory) only. No clinical trials.

4.6 Anti-Obesity Activity

Asimina triloba (pawpaw) contains various bioactive phytochemicals, including alkaloids, polyphenols, and acetogenins. One study investigated the effects of pawpaw seed extract (PSE) on obesity and plasma lipid concentrations in mice with high-fat diet (HFD)-induced obesity. Male C57BL/6J mice were fed a normal diet or a HFD for two weeks; groups were then fed an experimental diet containing 250 mg and 500 mg PSE/kg of HFD, respectively, for two weeks.

A significant decrease in body weight was observed in the high-dose PSE group compared to the HFD group. The perirenal, testicular, and total visceral fat masses of mice in the H-PSE group were consistently lower than those of mice in the HFD group. Administration of high-dose PSE decreased the expression of Fasn (encoding fatty acid synthase) and Dgat2 (encoding diglyceride acyltransferase 2) in testicular fat tissues. However, PSE administration did not decrease blood glucose and plasma cholesterol levels. These findings suggest that administration of PSE suppresses HFD-induced obesity in mice, while its hypoglycemic or cholesterol-lowering actions are less pronounced.

Evidence strength: Animal study (mice) only, published 2025. No human data.

4.7 Antiparasitic and Pesticidal Uses

The inhibition of mitochondrial respiration and subsequent ATP production may account for the broad biological activities exhibited by acetogenins and pawpaw extracts, ranging from anticancer, antimalarial, antiviral, antimicrobial, antiparasitic, to pesticidal activities. Due to the presence of acetogenins, the leaves, twigs, and bark of pawpaw trees can be used to make an organic insecticide.

Evidence strength: In vitro and laboratory bioassay data support pesticidal activity. No controlled human clinical studies.

5. Body Systems and Health Areas Associated with Paw Paw

• Oncology / Cellular metabolism: Inhibition of ATP synthesis in rapidly dividing cells via mitochondrial complex I blockade; antiangiogenic effects via HIF-1/VEGF pathway suppression (in vitro and animal models only).
• Immune surveillance: Proposed modulation based on in vitro data; no clinical confirmation.
• Dermatology / Ectoparasitology: Pediculicidal (anti-lice) activity; one small human study with a multi-ingredient shampoo formulation.
• Gastrointestinal system: Traditional use for digestive complaints, intestinal parasites; no clinical trial data.
• Metabolic health: Preliminary animal research suggesting anti-obesity effects via modulation of fatty acid synthesis gene expression.
• Antimicrobial defense: In vitro activity against certain bacterial strains (C. xerosis, C. perfringens).
• Neurological system (adverse — see Safety): Documented neurotoxic effects of acetogenins, particularly annonacin, on cortical neurons in vitro.

6. Dosage Forms and Dosages Reported in Studies

Clinical trials are lacking to provide guidance on dosing, and concerns of toxicity exist. The appropriate dose of American pawpaw depends on several factors such as the user's age, health, and several other conditions. At this time there is not enough scientific information to determine an appropriate range of doses for American pawpaw.

The following dosage parameters appear in the published research literature:

• Anti-lice shampoo (human study): Applying a shampoo that contains American pawpaw, thymol, and tea tree oil to the head up to three times over 16 days.
• Anti-obesity mouse study: L-PSE and H-PSE groups were fed an experimental diet containing 250 mg and 500 mg PSE/kg of HFD, respectively, for two weeks.
• In vitro anti-HIF-1 assay: Pawpaw crude extract and the acetogenins 10-hydroxyglaucanetin, annonacin, and annonacin A inhibited hypoxia-induced HIF-1 activation with IC50 values of 0.02 μg/mL, 12 nM, 13 nM, and 31 nM, respectively, in T47D cells.
• Annonacin concentration in fruit pulp: The average concentration of annonacin in the fruit pulp was 0.0701 ± 0.0305 mg/g.
• Neurotoxic acetogenin concentrations by LC-HRMS: The extraction of annonacin and squamocin from lyophilized fruit pulp was optimal at 100°C with 7.72 and 0.162 mg/g, respectively.

No standardized therapeutic dosing regimen has been established in any peer-reviewed clinical guideline.

7. Safety Considerations and Interactions

Neurotoxicity

The acetogenin annonacin, from the tropical annonaceous plant Annona muricata, is a lipophilic, mitochondrial complex I inhibitor reported to be more toxic than rotenone to mesencephalic neurons. Pawpaw fruit contains a high concentration of annonacin, which is toxic to cortical neurons. Crude fruit extract also induced neurotoxicity, highlighting the need for additional studies to determine the potential risks of neurodegeneration associated with chronic exposure to pawpaw products.

Purified annonacin (30.07 μg/mL) and crude EtOAc extract (47.96 μg/mL) induced 50% death of cortical neurons 48 hours post-treatment. Annonacin toxicity was enhanced in the presence of crude extract.

Both the crude fruit extract and annonacin, a major constituent of pawpaw, cause neurotoxicity in vitro.

Fruits, seeds, twigs, and leaves of several plants in the Annonaceae family contain neurotoxic compounds called acetogenins. Overconsumption of at least one of these fruits, graviola (Annona muricata), caused an atypical form of Parkinson's disease on the islands of Guadeloupe, Guam, and New Caledonia. The pawpaw (Asimina triloba) fruit might be of special concern in North America. Even though there are no epidemiological studies on the fruit, it has been suggested that it may also be neurotoxic. It contains much more annonacin than graviola, as well as many other acetogenins.

Pawpaw fruit contains neurotoxins (e.g., annonacin, squamocin) and has been linked to Parkinsonism in some reports; however, case studies are lacking.

Contact Dermatitis

The crude extract of the stem bark may cause contact dermatitis.

Pregnancy and Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Known Drug Interactions

No drug interactions are well documented. However, given that acetogenins are potent inhibitors of mitochondrial complex I — the same pathway targeted by some pharmaceutical agents — the theoretical potential for pharmacodynamic interactions with mitochondria-affecting drugs exists, though this has not been formally characterized in human studies.

Standardization Concerns

Acetogenin levels vary even by location of Asimina triloba trees, with some groves producing higher levels than others. Thus, it is important to ensure that any product is from the Asimina triloba species and that it is standardized — using an extraction process for acetogenins that ensures a guaranteed set amount is in the product.

Overall Safety Rating from Drugs.com

Although antiangiogenic, cytotoxic, antimicrobial, antioxidant, and pesticidal activities have been observed in vitro and in animal studies, published clinical trials are lacking to support its use for any indication. Clinical trials are lacking to provide guidance on dosing, and concerns of toxicity exist.

References

• McLaughlin JL. "Paw paw and cancer: annonaceous acetogenins from discovery to commercial products." Journal of Natural Products, 2008. PubMed.
• Coothankandaswamy V, et al. "The Alternative Medicine Pawpaw and Its Acetogenin Constituents Suppress Tumor Angiogenesis via the HIF-1/VEGF Pathway." Journal of Natural Products, 2010. PMC.
• Woo MH, et al. "Biologically active acetogenins from stem bark of Asimina triloba." PubMed, 1995.
• Potts LF, et al. "Annonacin in Asimina triloba fruit: Implication for neurotoxicity." Neurotoxicology, 2012. ScienceDirect.
• Luzzio FA & Monsen PJ. "Determination of Neurotoxic Acetogenins in Pawpaw (Asimina triloba) Fruit by LC-HRMS." PubMed, 2015.
• Nam JS, et al. "The growth-inhibitory effects of pawpaw (Asimina triloba [L.] Dunal) roots, twigs, leaves, and fruit against human gastric (AGS) and cervical (HeLa) cancer cells and their anti-inflammatory activities." Molecular Biology Reports, 2021. PubMed.
• Nam JS, et al. "Phenolic Profiles, Antioxidant and Antimicrobial Activities of Pawpaw Pulp (Asimina triloba [L.] Dunal) at Different Ripening Stages." Journal of Food Science, 2019. PubMed.
• Ratnayake S, et al. "Evaluation of various parts of the paw paw tree, Asimina triloba (Annonaceae), as commercial sources of the pesticidal annonaceous acetogenins." PubMed, 1992.
• Takano S, et al. "Pawpaw (Asimina triloba) Seed Extract Suppresses High-Fat Diet-Induced Obesity in Mice." International Journal of Molecular Sciences, 2025. PMC.
• Memorial Sloan Kettering Cancer Center. "American Pawpaw." Integrative Medicine Herb Database.
• Drugs.com. "Pawpaw Uses, Benefits & Dosage." Natural Products Database (medically reviewed April 21, 2026).
• ScienceDirect. "North American pawpaw (Asimina triloba L.) fruit: A critical review of bioactive compounds and their bioactivities." Food Research International, 2024.
• McLaughlin JL. "Paw Paw and Cancer: Annonaceous Acetogenins from Discovery to Commercial Products." Journal of Natural Products (ACS), 2008.
• Wikipedia. "Asimina triloba." (Used for general botanical and ethnobotanical context only.)