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Background & General Info
The northern prickly ash, or Zanthoxylum americanum, is a shrub belonging to Rutaceae or the citrus family, which explains the lemon-like scent of its foliage and flowers. It is native to the central and eastern forest edges, meadows, ridges, and woodlands of Canada and the United States and is in fact the northernmost representative of the citrus family in the New World. The prickly ash received its name from its compound leaves that superficially resemble those of ash trees (Fraxinus sp.) and its several prickles (or short, sharp-pointed outgrowth on its bark). 
The prickly ash is a deciduous shrub with compound dark green leaves that drop off during winter, membranous leaflets, and axillary flower clusters.  Its leaves are also described to be bitter aromatic, with crenate margins.  This plant characteristically possesses prickles (hence its name), hairy buds, and stalked follicles that transition in color from green, to red, to deep blue, to black. The fragrant, greenish or yellow-green flowers are used by the plant to attract bees and other insects for pollination. 
History & Traditional Use
Based on the ethnomedicinal system of indigenous North Americans, the prickly ash can be used for fungal infections and applied as medicine for arthritic and rheumatic conditions, digestive problems, and leg ulcers.  Its berries are purported to bear carminative (flatulence-relieving) and antispasmodic properties and can be used as laxative against dyspepsia and indigestion.  Furthermore, the prickly ash is regarded as a “warming” herb that favorably stimulates the circulation; the native North American Indians also use it to especially alleviate rheumatism and toothache.  The seeds and bark of the northern prickly ash are described as aromatic, hot, and astringent and are considered a remedy for toothache by the natives of the coasts of Virginia and the Carolinas. It has also been reported that the Indians greatly regarded the plant to “radically remove impurities of the blood,” whereas Andre Michaux reported in 1795 that the root of the tree is good “for obstructions of the liver and spleen”. 
General Herbal Uses
Extracts acquired from the bark and follicles of the prickly ash are valuable in traditional phytomedicine, which can be used as a stimulant and as remedy for gastrointestinal or digestive disorders, chronic rheumatism, skin disorders, typhoid, and diseases associated with blood impurities.  When chewed, the bark of this plant can allegedly relieve toothaches, and a tea can be produced from the follicles, which can be consumed to soothe sore throats and induce diuresis.  According to Grieve, the plant, especially its fruits, is a diaphoretic and stimulating tonic that can be helpful for debilitating conditions of the stomach and digestive system and can produce “arterial excitement,” which can be of use in the treatment of fevers, ague (malarial fever), and poor circulation. 
Ju et al. (2001) isolated four pyranocoumarins from the northern prickly ash, namely, dipetaline, alloxanthoxyletin, xanthoxyletin, and xanthyletin, aside from two lignans (sesamin and asarinin).  An activity-directed fractionation performed by a 1990 study isolated five furanocoumarins, namely, cnidilin, imperatorin, isoimperatorin, psoralen, and xanthotoxin. 
A 1990 study revealed the cytotoxicity of crude extracts derived from the berries of Zanthoxylum americanum against human tumor cells, with the furanocoumarins isoimperatorin, psoralen, and xanthotoxin having been found to be bioactive in bioassays.  Findings from a 2001 study indicated cytotoxicity against leukemia cells by pyranocoumarins and lignans isolated from the extracts of northern prickly ash. These pyranocoumarins (dipetaline, alloxanthoxyletin, xanthoxyletin, and xanthyletin) and lignans (sesamin and asarinin) effectively prevented the incorporation of tritiated thymidine into human leukemia cells, with dipetaline being the most active with an IC50 value of 0.68 ppm. 
Xanthoxyletin has been validated by Rasul et al. (2011) to be a promising anticancer or antiproliferative compound that triggers cell cycle arrest and apoptosis in human gastric adenocarcinoma SGC-7901 cells. This compound dose-dependently inhibits the cancer cells by inducing their DNA damage, apoptosis through mitochondrial dysfunction, and cell cycle arrest at S phase. Moreover, xanthoxyletin augments the production of reactive oxygen species in adenocarcinoma SGC-7901 cells.  Sesamin has also been proven to display antiproliferative and anti-angiogenic effects on cancer cells and has been confirmed in the study of Siao et al. (2015) to prevent the development of breast cancer by modulating apoptotic signal pathways and suppressing tumor cell growth. In MTT assay, a dose-dependent reduction in cell viability of human breast cancer MCF-7 cells was observed following sesamin treatment, as well as an increase in LDH release and apoptosis. 
Bafi-Yeboa et al. (2005) found broad-spectrum light-dependent antifungal action from all extracts derived from the leaves, fruits, stem, bark, and roots of prickly ash. These extracts inhibited the growth of at least eight opportunistic and systemic fungal strains in a disk diffusion assay (600 µg/disk), which include Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. Overall, extracts from prickly ash fruits and leaves were considered most active, which contain high amounts of furanocoumarin.  According to Smith et al. (2004), the furanocoumarin content of extracts of northern prickly ash positively correlates to its antifungal effect. In their study, the furanocoumarins 5-methoxypsoralen and psoralen specifically inhibited DNA polymerization, suggesting that furanocoumarins suppressed the replicative functions of genomes or of regions within the genome that differ in base composition. Since the extracts from husks of northern prickly ash more greatly inhibited DNA polymerization than individual furanocoumarins, the researchers concluded that aside from furanocoumarins, there are other inhibitory or antifungal compounds present in the northern prickly ash. 
Contraindications, Interactions, And Safety
The northern prickly ash is best avoided during pregnancy except when under the supervision of a qualified healthcare practitioner since the plant is an emmenagogue, or an herb that can stimulate or increase blood flow to the pelvic area and uterus. Safety during lactation has not also been decisively established, although there has been no mention in scientific or traditional literature about concerns on its use while breastfeeding. So far, there have been no reports of cases of prickly ash toxicity or occurrence of adverse events in humans, as well as suspected drug interactions. 
 "Zanthoxylum americanum P. Mill.: common prickly-ash," Go Botany. https://gobotany.newenglandwild.org/species/zanthoxylum/americanum/
 W. H. Duncan and M. B. Duncan, Trees of the Southeastern United States, Athens: The University of Georgia Press, 1988.
 N. Bafi-Yeboa, J. Arnason, J. Baker and M. Smith, "Antifungal constituents of northern prickly ash, Zanthoxylum americanum Mill.," Phytomedicine, vol. 12, no. 5, p. 370–377, 2005. https://www.ncbi.nlm.nih.gov/pubmed/15957372
 A. Chevallier, The Encyclopedia of Medicinal Plants, London: Dorling Kindersley, 1996.
 M. Grieve, A Modern Herbal, C. Leyel, Ed., New York: Barnes & Noble Books, 1996, p. 70–71.
 "Prickly Ash, Zanthoxylum americanum; (Rutaceae)," The Complete Writings of Dr. John R. Christopher. http://online.snh.cc/files/2100/HTML/prickly_ash__zanthoxylum_americanum.htm
 S. Foster and J. Duke, A Field Guide to Medicinal Plants: Eastern and Central North America, Boston: Houghton Mifflin Company, 1990.
 M. Grieve, A Modern Herbal, London: Penguin, 1984.
 Y. Ju, C. Still, J. Sacalis, J. Li and C. Ho, "Cytotoxic coumarins and lignans from extracts of the northern prickly ash (Zanthoxylum americanum)," Phytotherapy Research, vol. 15, no. 5, p. 441–443, 2001. https://www.ncbi.nlm.nih.gov/pubmed/11507740
 Q. Saqib, Y. Hui, J. Anderson and J. McLaughlin, "Bioactive furanocoumarins from the berries of Zanthoxylum americanum," Phytotherapy Research, vol. 4, no. 6, p. 216–219, 1990. http://onlinelibrary.wiley.com/doi/10.1002/ptr.2650040604/pdf
 A. Rasul, M. Khan, B. Yu, T. Ma and H. Yang, "Xanthoxyletin, a coumarin induces S phase arrest and apoptosis in human gastric adenocarcinoma SGC-7901 cells," Asian Pacific Journal of Cancer Prevention, vol. 12, no. 5, p. 1219–1223, 2011. https://www.ncbi.nlm.nih.gov/pubmed/21875271
 A. Siao, C. Hou, Y. Kao and K. Jeng, "Effect of sesamin on apoptosis and cell cycle arrest in human breast cancer mcf-7 cells," Asian Pacific Journal of Cancer Prevention, vol. 16, no. 9, p. 3779–3783, 2015. https://www.ncbi.nlm.nih.gov/pubmed/25987037
 M. L. Smith, P. Gregory, N. F. Bafi-Yeboa and J. T. Arnason, "Inhibition of DNA polymerization and antifungal specificity of furanocoumarins present in traditional medicines," Photochemistry and Photobiology, vol. 79, no. 6, p. 506–509, 2004. http://onlinelibrary.wiley.com/doi/10.1111/j.1751-1097.2004.tb01267.x/full
 Z. Gardner and M. McGuffin, American Herbal Products Association’s Botanical Safety Handbook, 2nd ed., Boca Raton, Florida: CRC Press, 2013.
Article researched and created by Dan Albir for herbs-info.com. © herbs-info.com 2018
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