JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY A RTICLE
J. Agric. Food Chem. 2009, 57, 8339–8343 DOI:10.1021/jf9018239
8339
KIRK W. POMPER,*† JEREMIAH D. LOWE,† SHERI B. CRABTREE,† AND WILLIAM KELLER‡
Downloaded by UNIV OF KENTUCKY on September 16, 2009 | http://pubs.acs.org Publication Date (Web): August 27, 2009 | doi: 10.1021/jf9018239
\daggerLand Grant Program, Atwood Research Facility, Kentucky State University, Frankfort, Kentucky 40601-2355, and\daggerHealth Sciences and Educational Services, Nature's Sunshine Products, Inc., 1655 North Main Street, Spanish Fork, Utah 84660
The North American pawpaw [Asimina triloba (L.) Dunal] is a tree fruit in the early stages of commercial production in the United States. This plant contains annonaceous acetogenins in the twigs, unripe fruit, seeds, roots, and bark tissues, which display antitumor, pesticidal, antimalarial, anthelmintic, piscicidal, antiviral, and antimicrobial effects, suggesting many potentially useful applications. However, commercial development of these compounds, based on twig extracts, has been problematic due to limited availability of biomass for extraction. Additionally, acetogenin compounds contained in fruit of pawpaw relatives (soursop or Annona muricata) and tea made from the leaves of these plants may lead to an increased risk of atypical Parkinsonism later in life with overconsumption of these compounds. Therefore, the objectives of this study were (1) to determine if extracts of ripe pawpaw fruit pulp displayed acetogenin activity, (2) to identify potential acetogenin compounds in the fruit tissue, and (3) to determine if the acetogenin activity varied in diverse pawpaw genotypes and closely related Annona species. Extracts of ripe fruit had total extract weights and bioactivity using the brine shrimp bioassay similar to those from ‘NC-1’ pawpaw twig tissue. Pulp from soursop, cherimoya, and several additional pawpaw cultivars (‘Mitchell’, ‘Overleese’, ‘NC-1’, ‘Zimmerman’, ‘Wells’, and ‘Sunflower’) also displayed bioactivity, but peach or banana pulp did not. Ripe pawpaw pulp extract subjected to HPLC-MS analysis identified three prominent acetogenins: asimicin, bullatacin, and bullatalicin. This study points to pawpaw fruit pulp serving as a new biomass source for the extraction of acetogenin compounds for product development. An assessment of the potential human health risk of overconsumption of fruit and acetogenin bioavailability and degradation studies should be pursued.
KEYWORDS: Antitumor; pesticidal; antimalarial; anthelmintic; piscicidal; antiviral; antimicrobial; pawpaw cultivars
*Author to whom correspondence should be addressed [telephone (502) 597-5942; fax (502) 597-6381; e-mail kirk.pomper@kysu.edu]. ointment for the treatment of oral herpes (HSV-1) and other skin afflictions (1).
ointment for the treatment of oral herpes (HSV-1) and other skin afflictions (1).
Acetogenins, such as asimicin and bullatacin, may prove to be important compounds for combating specific cancers in the future. Oberlies et al. (4) evaluated 14 acetogenins against the MCF-7/Adr cell line to establish their structure—activity relationships (SARs); of the 14 acetogenins, 13 were generally more potent than all three of the standard drugs. Bullatacin was 258 times more cytotoxic against the MCF-7/Adr cell line than adriamycin. Asimicin, bullatacin, and the bullatacinones were also active in laboratory mice bearing implanted L-1210 leukemia (5). Certain acetogenins are often selectively cytotoxic to one or only a few cancer cell lines (6, 7). Recently, Cuendet et al. (8) tested pawpaw twig extracts containing bullatacin, asimicin, and trilobacin in the N-methyl-N-nitrosourea-induced mammary carcinogenesis model. With Sprague-Dawley rats given a diet containing pawpaw extract (1250 and 2500 mg/kg of diet; based on maximum tolerated dose studies), mammary tumor latency was increased from 55 to 66 days. Insecticides based on
©2009 American Chemical Society
Published on Web 08/27/2009
Annonaceous acetogenins are a large class of unique structurally homogeneous polyketide (C32 or C34 fatty acid) compounds found in the Annonaceae family, which includes both genera Annona and Asimina (1, 2). These compounds are potent inhibitors of mitochondrial (complex I) as well as cytoplasmic (anaerobic) production of adenosine triphosphate (ATP) and related nucleotides. Acetogenin compounds are powerful cytotoxins and display in vivo antitumor, pesticidal, antimalarial, anthelmintic, piscicidal, antiviral, and antimicrobial properties, suggesting many potentially useful applications (1–3). Commercial development of these compounds could range from pesticides to topical or dietary supplement products. Applications and commercial products include a shampoo for treating infestations of head lice, fleas, and ticks, a series of pesticidal sprays, and an
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