Pawpaw
Asimina triloba (L.) Dunal. Family: Annonaceae
Pawpaw , Custard apple , Poor man's banana , Indiana banana
 
Clinical Overview
Uses
Pawpaw has historically been used for food, fishing nets, and medicine. It exhibits cytotoxic and pesticidal activities.

Dosing
Pawpaw has been used in homeopathy. Higher doses run a substantial risk of toxicity; therefore, pawpaw cannot be recommended.

Contraindications
No longer considered safe.

Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.

Interactions
None well documented.

Adverse Reactions
May cause contact dermatitis in certain people.

Toxicology
Due to its cytotoxic and pesticidal activities, pawpaw may be toxic to humans.

 
Botany
The pawpaw is a small, North American tree which grows from approximately 3 to 12 meters high. It is common in the temperate woodlands of the eastern United States. Its large leaves are droopy and give the plant a tropical appearance. The dark brown, velvety flowers, approximately 5 cm across, grow in umbrella-like whorls, similar to some magnolia species, and can bloom for up to 6 weeks. Pawpaw fruit is smooth-skinned, yellow to greenish-brown in color, measuring from approximately 8 to 15 cm long. It can reach up to 0.45 kg in weight. It resembles that of a short, thick banana, and is also similar in nutrient value. The yellow, soft, “custard-like” pulp is edible but sickly sweet in flavor and contains dark seeds. 1,  , 2,  , 3,  , 4
 
History
The pawpaw has been used as food for Native Americans. The thin, fibrous, inner bark has been used to make fish nets. 1,  , 3,  The bark was also used as medicine because it contains useful alkaloids. 3
 
Chemistry
The bark, roots, twigs, and seeds of the pawpaw plant contain acetogenins, long-chain, aliphatic compounds with 35 to 39 carbon atoms ending with a gamma-lactone, cyclized in tetrahydrofuran rings. 5,  They are polyketide-derived molecules and are unique to the Annonaceae family. Thus far, more than 230 acetogenins from Asimina and other genera have been identified. 6,  Acetogenins are known for their cytotoxic, antitumor, immunosuppressive antimalarial, pesticidal, antibacterial, and antifeedant properties. 5,  , 6
Known bioactive compounds from pawpaw bark include asimicin, bullatacin, bullatacinone, N-p-coumaroyltyramine, N-trans-feruloyltyramine, and (+)-syringaresinol. Trilobacin, a highly cytotoxic acetogenin, and trilobalicin and its ketolactones (2,4-cis and 2,4-trans-trilobacinone) have also been identified. 7,  , 8,  In addition, acetogenins cis- and trans-annonacin-a-one, cis- and trans-gigantetrocinone, trans-isoannonacin, and squamolone have been determined. 9,  The acetogenins asimin, asiminacin, and asiminecin (all structural isomers) from pawpaw stem bark extracts were determined and also found to have highly cytotoxic properties. 10,  Similar findings were described for acetogenins bis-tetrahydrofurans, 11,  asiminocin ([30s]-hydroxy-4-deoxyasimicin), 12,  (2,4-cis)- and (2,4-trans)-asimicinone. 13,  In addition, acetogenins asimilobin, cis- and trans-murisolinones, and cis- and trans-bullatacinones have been isolated from pawpaw seeds. 14,  Asiminine and analobine alkaloids have also been found. 3,  A variety of essential oils and other extracts from the plant has been reported. 15
 
Uses and Pharmacology
The pawpaw acetogenins have consistently exhibited cytotoxic, antitumor, pesticidal, and antimicrobial activities. Animal and clinical studies have not been done. Some in vitro studies have been performed.
Brine shrimp lethality bioassay or “test” (BSLT) is a screening tool used to predict cytotoxic and pesticidal activity. Young shrimp, Artemia salina , are placed in brine where their eggs hatch within 48 hours. Extracts of test-plant material are then put in shrimp-containing vials where survivors are microscopically counted. LC50 values are then calculated to determine the potential killing activity of, in this case, pawpaw extracts. 16
In several studies performed in this manner it was found that specific acetogenins exhibited potent cytotoxicity. 7,  , 9,  , 11,  , 14,  Examples include acetogenin's cytotoxic potential against lung carcinoma, breast carcinoma, and colon adenocarcinoma. 9,  Certain seed extracts also possessed cytotoxic actions comparable with doxorubicin against 6 human solid tumor cell lines. 14
Of all the acetogenins, the adjacent-bis-THF-ring compounds are the most potent, showing cytotoxic activity against human lung and breast tumor cell lines with up to a million times the potency of doxorubicin. 8,  Compound asiminocin, a pawpaw acetogenin isolate from stem bark was highly inhibitory against 3 human cell lines, with over a billion times the potency of doxorubicin. 12,  The mechanism of action is via potent inhibition of mitochondrial NADH:ubiquinone oxidoreductase, thus causing a decrease in cellular ATP levels. 6,  , 10
Various pawpaw tree parts were tested for pesticidal potential. It was found that small twigs yielded the most potent extract, while the leaves were the least potent. Unripe fruits, seeds, root wood and bark, and stem bark were also notably potent. 17 ,  A caterpillar-laden tree was sprayed with a pawpaw bark extract and 30 minutes later the majority of insects had died and fallen from the tree. Phlox plants infested with mildew fungus were also sprayed with pawpaw preparation and 10 days later improvement was markedly observed. Pawpaw tree samplings were collected, expressing monthly variation in pesticidal activity. All of these are examples of the plant's beneficial properties. The pawpaw tree is usually insect- or disease-resistant because of its acetogenin content, which deters the feeding of many organisms. 6
 
Administration & Dosage
Pawpaw has been used in homeopathy. Higher doses run a substantial risk of toxicity; therefore, pawpaw cannot be recommended.
 
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.
 
Interactions
None well documented.
 
Adverse Reactions
Handling the fruit may produce a skin rash in sensitive individuals. 3,  The sensitizing potential of the pawpaw was examined in guinea pigs; the crude extract of the stem bark was found to be a weak sensitizer and to elicit allergic contact dermatitis. This report also determined the active compound asimicin to be a weak irritant. 18
 
Toxicology
Due to its cytotoxic and pesticidal activities, pawpaw may be toxic to humans.
 
References
 

1. Hocking G. A Dictionary of Natural Products . Medford, NY: Plexus Publishing Inc., 1997;80.  PubMed

 

2. Davidson A. Fruit-A Connoisseur's Guide and Cookbook . NY, NY: Simon and Schuster, 1991;123-124.

 

3. NNGA library. http://www.icserv.com/nnga/pawpaw.htm . Pawpaw and acetogenins.

 

4. Univ. of Kentucky. http://www.pawpaw.kysu.edu . The return of the pawpaw.

 

5. Bruneton J. Pharmacognosy, Phytochemistry, Medicinal Plants . Paris, France: Lavoisier, 1995;156.

 

6. Johnson H, et al. Progress in New Crops . Arlington, VA: ASHS Press, 1996;609-614.

 

7. Zhao G, et al. Additional bioactive compounds and trilobacin, a novel highly cytotoxic acetogenin, from the bark of Asimina triloba. J Nat Prod . 1992;55:347-356.  PubMed

 

8. He K, et al. Additional bioactive annonanaceous acetogenins from Asimina triloba (Annonaceae). Bioorg Med Chem . 1997;5:501-506.  PubMed

 

9. Zhao G, et al. Biologically active acetogenins from stem bark of Asimina triloba. Phytochemistry . 1993;33:1065-1073.  PubMed

 

10. Zhao G, et al. Asimin, asiminacin, and asiminecin: novel highly cytotoxic asimicin isomers from Asimina triloba. J Med Chem . 1994;37:1971-1976.  PubMed

 

11. He K, et al. Three new adjacent bis-tetrahydrofuran acetogenins with four hydroxyl groups from Asimina triloba. J Nat Prod . 1996;59:1029-1034.  PubMed

 

12. Zhao G, et al. The absolute configuration of adjacent bis-THF acetogenins and asiminocin, a novel highly potent asimicin isomer from Asimina. Bioorg Med Chem . 1996;4:25-32.

 

13. Zhao G, et al. (2,4–cis)-asimicinone and (2,4–trans)-asimicinone: two novel bioactive ketolactone acetogenins from Asimina triloba (Annonaceae). Nat Toxins . 1996;4:128-34.

 

14. Woo M, et al. Asimilobin and cis- and trans-murisolinones, novel bioactive Annonaceous acetogenins from the seeds of Asimina triloba. J Nat Prod . 1995;58:1533-1542.  PubMed

 

15. Derevinskaya T, et al. Some problems of the quality of drug-technical raw material of Asimina triloba. Farm Zh . 1983;38:49-52.

 

16. Colegate S, et al. Bioactive Natural Products. Boca Raton, FL: CRC Press, 1993;15-17.

 

17. Ratnayake S, et al. Evaluation of various parts of the paw paw tree, Asimina triloba (Annonaceae), as commercial sources of the pesticidal annonaceous acetogenins. J Econ Entomol . 1992;85:2353-2356.  PubMed

 

18. Avalos J, et al. Guinea pig maximization test of the bark extract from pawpaw, Asimina triloba (Annonaceae). Contact Dermatitis . 1993;29:33-35.  PubMed