Botanical Name: Zanthoxylum americanum, Rutaceae

Botanical synonyms:  Xanthoxylum fraxineum, X. fraxinifolium, X. ramiflorum, X. tricarpum, Thylax fraxineum

Common names: Prickly Ash, Northern Prickly Ash, Toothache Bark, Toothache Tree, Toothache Bush, Yellowwood, Hercules Club, Sea Ash, Pepperwood, Wild Orange.

Similar species: Zanthoxylum clava-herculis (Southern Prickly Ash), Zanthoxylum piperitum, Zanthoxylum armatum (Tumburuh-India), Zanthoxylum bungeanum (Chuan jiao-China).  Many species of Zanthoxylum are found all over the world, and most have very similar properties.

Plant description: Zanthoxylum is an aromatic, spiny, thicket-forming deciduous shrub or small tree, typically attaining a height of between 2.5 and 3.5 meters, some specimens up to 7.5 m.  The alternate branches are armed with strong brown prickles, about 1-2 cm long, cone-shaped with a broad base, and found irregularly throughout the tree but frequently at the base of young branches. The leaves are compound, oddly pinnate, dark green leaves up to 3 cm long with 5-11 leaflets each.  Prickly ash is dioecious, the male and female flowers appearing on separate trees, borne in axillary clusters on old wood. The greenish-yellow, rather inconspicuous flowers bloom in spring before the leaves emerge, and are highly aromatic and quite attractive to bees.  Female flowers give rise to clusters of rounded, reddish-brown berry-like fruits (follicles) that mature in late summer, containing 1-2 shiny black seeds in each follicle.

Habitat, ecology and distribution: Common Prickly Ash or Northern Prickly Ash is common in woods and thickets, in moist rocky soils and along river banks from Virginia to Kansas, northward into Ontario and Quebec.  The much larger Southern Prickly Ash (Z. clava-herculis) grows along streams from southern Virginia down into Florida, westward into Texas and Arkansas.

Part used: whole plant; fruit, bark, root bark

History: Prickly Ash derives its name for its prickly branches and similar leaves to ash, which rather more resemble elder.  It was popular as a stimulant long before its virtues were extolled by the eclectics, and was an important remedy in the Thomsonian materia medica.  Although the bark is often described as officinal, Colby only mentions the fruit in his New Guide To Health (1846), which are considered by many herbalists to be the most stimulating part of the plant. Its common name Toothache Tree refers to the usage of the follicles (pericarp) and bark, which were chewed to stimulate the flow of saliva and relieve pain.  This practice extends to species found all over North America, as well as in India and China.  Its common name Yellowood refers to the genus name Zathoxylum, from the Greek xanthos, meaning yellow, and xylon for wood. All parts of the shrub are highly aromatic, pungent, and more or less medicinal, and the leaves and berries have a pleasant lemon scent.  Zanthoxylum at one time furnished the peppery taste in Chinese Szechuan cuisine, but has since been replaced by the more pungent Cayenne.

Constituents: Note: constituents for both species of Zanthoxylum (i.e. americanum and clava-herculis) are represented because they are used more or less interchangeably by herbalists.  Prickly Ash is noted for its isoquinoline alkaloids, including chelerythrine, magniflorine, lauriflorine, nitidine, candicine, tembertarine and acetylanonaine. Other important constituents include the isobutylamides herculin and neoherculin (echinacein), which provide for the characteristic tingling sensation on the tongue when Zanthoxylum is tasted.  By organolepsis the seeds appear to contain highest amounts of amounts of isobutylamides, and the bark with higher amounts of the isoquinoline alkaloids.  Other constituents include lignans (asarinin and sesamin), resins, tannins and an acrid volatile oil. The coumarins xanthyletin, xanthoxyletin and alloxanthoxyletin have been identified in Z. americanum, but appear to be absent in Z. clava-herculis (Newall et al 1996, 220; Bradley 1992, 177).

Medical Research:
•Gastrointestinal: A methanolic extract of the Zanthoxylum rhetsa stem bark, given orally to mice at doses of 250 and 500 mg/kg, significantly reduced abdominal contractions induced by acetic acid and diarrhea induced by castor oil in mice (Rahman et al 2002). A crude ethanolic extract of Zanthoxylum hyemale was determined to exhibit antispasmodic activity in isolated rat ileum, whereas isolated quinoline alkaloids and an aromatic amide from the same plant were determined to be inactive when tested individually (de Moura et al 2002). The herbal medicine Dai-Kenchu-To, composed of Zanthoxylum fruit, Ginseng root, and dried Ginger rhizome, was determined to be a clinically useful medicament for uncomplicated post-operative adhesive intestinal obstruction.  Researchers investigated the effect of Dai-Kenchu-To and determined that Zanthoxylum fruit elicited phasic contractions, primarily in the duodenum and jejunum (Shibata et al 1999)
•Central nervous system: A methanol extract of Zanthoxylum schinifolium stems showed potent inhibitory activity against monoamine oxidase (MAO) in mouse brain (Jo et al 2002).
•Cardiovascular: Six new coumarins, schinicoumarin, acetoxyaurapten, epoxycollinin, schininallylol, schinilenol and schinindiol, along with seven known coumarins, aurapten, collinin, epoxyaurapten, hydrangetin, umbelliferone, acetoxycollinin and aesculetin dimethyl ether, three known alkaloids, norchelerythrine, dictamnine and skimmianine, and two triterpenoids, beta-amyrin and friedelin, were isolated from the bark of Zanthoxylum schinifolium. The structures of these compounds were elucidated by spectral analyses. Schinicoumarin, acetoxyaurapten, schininallylol, aurapten, collinin,   (-)-acetoxycollinin and dictamnine displayed strong inhibitory activity on platelet aggregation in vitro (Chen et al 1995).  The ether fraction of an aqueous extract of the roots of Zanthoxylum xanthoxyloides (antisickling fraction), demonstrated antisickling inhibitory activity at low concentrations, while neither affecting NADP+-linked glucose-6-phosphate and 6-phosphogluconate dehydrogenasesthe nor disrupting the cell membrane to the extent of causing leakage to the media (Osoba et al 1989).
•Antiinflammatory: Zanthoxylum bungeanum was tested for its inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated J774.1 macrophages and in LPS/interferon (IFN)-gamma-stimulated mouse peritoneal exudate macrophages. A methanol extract of Zanthoxylum demonstrated significant inhibition in J774.1 macrophages, and inhibited the NO production in mouse peritoneal exudate macrophages.  The activity was found to be mainly due to the inhibition on iNOS mRNA expression (Tezuka et al 2001). A methanolic extracts of Zanthoxylum nepalensis was found to significantly inhibit the biosynthesis of leukotriene B(4) in bovine polymorphonuclear leukocytes when compared to 24 other screened plant extracts (Kumar et al 2000).
•Anticancer: Four pyranocoumarins; dipetaline, alloxanthoxyletin, xanthoxyletin and xanthyletin; and two lignans; sesamin and asarinin were isolated from Northern Prickly Ash. To varying degrees, all inhibited the incorporation of tritiated thymidine into human leukemia (HL-60) cells, with dipetaline being the most active, followed by alloxanthoxyletin, sesamin, asarinin, xanthoxyletin and xanthylletin (Ju et al 2001).
•Antimicrobial: Two benzophenanthrene alkaloids, 8-acetonyldihydronitidine and 8-acetonyldihydroavicine isolated from Zanthoxylum tetraspermum stem bark, demonstrated significant antibacterial activity, while 8-acetonyldihydronitidine, along with another isolated constituent liriodenine, demonstrated strong antifungal properties in vitro. Other constituents savinin and sesamin exhibited significant insecticidal activity (Nissanka et al 2001). A crude ethanol extract from the leaves of Zanthoxylum liebmannianum exhibited inhibitory effect on the reproduction of trophozoites of Entamoeba histolytica and Giardia lamblia (Arrieta et al 2001). A decoction of the stem bark of Zanthoxylum liebmannianum was shown to be toxic to intestinal nematode eggs and Ascaris suum in infected sheep (Navarrete and Hong 1996).  Chelerythrine has deomstrated significant antimicrobial properties against gram-positive bacteria and Candida albicans in vitro (Newall et al 1996 221).

Toxicity: No toxicity data for Zanthoxylum could be found.  The isolated constituent chelerythrine is reported to have an LD50 of 18.5 mg/kg by intravenous injection and 95 mg/kg by subcutaneous injection in mice.  The oral administration of 10 mg/kg of chelerythrine demonstrated no toxic effects after ten days of administration in animal models (Newall et al 1996 221).

Herbal action: capillary relaxant, nervine stimulant, circulatory stimulant, diaphoretic, antirheumatic, carminative, antispasmodic, sialogogue, alterative, antispetic

Indications: muscle spasm, intermittent claudication, chilblains, varicose veins, Raynauld's disease, arthritis, rheumatism, neuraligia, sickle cell anemia, toothaches, gum disease, gastric deficiency, colic, abdominal dystension, constipation, diarrhea, dysentery, postpartum pain, dysmenorrhea, coryza, flu, fever, lymphatic congestion, catarrh

Contraindications and cautions: pregnancy; irritation or ulceration of the gastrointestinal mucosa; concurrent usage with blood-thinning medications such as warfarin (Tillotson 181, 2001).

Medicinal uses: There is some difference between the use of the bark and the berries, likely due to the different constituent profiles of each.  The berries are far more stimulating than the bark, but do not contain the bitter properties that make the latter useful for biliary disorders.  As such, either the berries or bark should be chosen for the best purposes. In small doses, Felter and Lloyd state that Prickly Ash is indicated in atonic states of the mucus membranes, with relaxation and hypersecretory states (1893).  In larger doses however, Prickly Ash bark is indicated in depressive states of the nervous system, with capillary congestion and sluggish circulation, dryness of the mouth and pharynx, gastric deficiency with hyposecretory states, abdominal distention and gas, uterine cramping and pain, and neuralgia. Felter and Lloyd state that for "…painful bowel disorders, the preparations of the berries are to be preferred" (1893), as the stimulant properties of the plant are better employed.  Prickly Ash is much like the other capillary stimulants, stronger than Zingiber but decidedly weaker than Capsicum.  Prickly Ash works to relax the periphery by stimulating the small arteries and capillaries, directing its action to the circulation, skin, salivary glands, and lymphatic system, but also to the mucus membranes and kidneys. The bark and berries when chewed are remarkable sialagogues, and when swallowed provides for a sense of warmth in the stomach, increasing biliary and pancreatic activity (esp. the bark).  Felter and Lloyd state that "…under its action the kidneys become more active, and an increased urinary product results…cardiac action is increased, the pulse becomes slightly accelerated, and the integumentary glands give out an abundant secretion" (1893). Due to its pronounced sialagogue properties, Prickly Ash is an important remedy in disorders of the mouth and throat, as well as of the digestive tract. It can be a useful remedy in chronic pharyngitis and post-nasal catarrh, taken both internally and as a decoction to be used locally. As a treatment in toothache an extract of Prickly Ash berries can be used as mouthwash, particularly in cases of inflammation with scanty buccal secretions.  As a preventative the berries can be reduced to a fine powder and used as a dentifrice. Prickly Ash is also warranted in constipation due to deficient intestinal secretions, particularly when accompanied by colic and flatulence.  It is similarly used to restore bowel function after dysentery, and is indicated in jaundice from biliary congestion.  Prickly Ash was a favorite medicament of the eclectic John King, who found it of great service as a remedy for epidemic dysentery, Asiatic cholera, abdominal distension and peritoneal inflammation, given both orally and by injection.  For infantile colic or infectious dysentery King mixed a tincture of the berries with olive oil and massaged it over the abdomen until relief was noted (Felter and Lloyd 1893). In the treatment of rheumatic complaints Felter and Lloyd state that Prickly Ash can be combined with Phytolacca, to assist in the removal of wastes through the lymphatic and renal systems.  Combined with antispasmodics such as Cimicifuga Prickly Ash is a good treatment in "debilitated patients" particularly in sciatica and myalgia, Prickly Ash is an important remedy for functional dysmenorrhoea, with severe pain and hypersensitivities. Prickly Ash is an important diaphoretic to resolve colds, flu, and fever. As a capillary stimulant Prickly Ash is useful remedy to resolve eruptive diseases, particularly in cases of "…retrocession of the eruption" (Felter and Lloyd 1893).  As a general stimulant to the nervous system, Prickly Ash is warranted in almost any case of debility or atony, with prostration and paralysis.  In the treatment of sickle-cell anemia, herbalist Alan Tillotson states that a Nigerian species of Zanthoxylum called fagara has been investigated for its usefulness in this disorder.  In his book The One Earth Herbal Sourcebook, Tillotson provides a few case histories in which the symptoms of sickle-cell anemia were completely alleviated by the use of Prickly Ash, but only as long as the medicament was being taken.  Tillotson suggests that this property may be due the coumarins and alkaloidal constituents (2001, 182).

Pharmacy and dosage:
•Fresh Plant Tincture: berries and/or bark, 1:2, 95% alcohol, 2-30 gtt, up to 3 mL
•Dry Plant Tincture: berries and/or bark, 1:5, 25% alcohol, 3 gtt upwards to 5 mL
•Decoction: 1:20, 30-120 mL
•Powder: 0.5-3 g
•Enema: decoction, 1:20, applied tepid and retained as long as possible

REFERENCES

Arrieta J, Reyes B, Calzada F, Cedillo-Rivera R, Navarrete A. 2001. Amoebicidal and giardicidal compounds from the leaves of Zanthoxylum liebmannianun Fitoterapia Mar;72(3):295-7
Bradley, Peter R. ed. 1992. British Herbal Compendium. Bournemouth, UK: British Herbal Medicine Association.
Cook, WM. H. 1869. The Physiomedical Dispensatory.  Cincinnati: self-published.  Digitized version available from http://medherb.com/cook/home.htm.
de Moura NF, Morel AF, Dessoy EC, Zanatta N, Burger MM, Ahlert N, Porto GP, Baldisserotto B. 2002. Alkaloids, amides and antispasmodic activity of Zanthoxylum hyemale. Planta Med Jun;68(6):534-8
Felter, HW and JU Lloyd. 1893. King's American Dispensatory. Digitized version available from http://www.ibiblio.org/herbmed/eclectic/kings/main.html.
Jo YS, Huong DT, Bae K, Lee MK, Kim YH. 2002 Monoamine oxidase inhibitory coumarin from Zanthoxylum schinifolium. Planta Med Jan;68(1):84-5
Ju Y, Still CC, Sacalis JN, Li J, Ho CT. 2001. Cytotoxic coumarins and lignans from extracts of the northern prickly ash (Zanthoxylum americanum). Phytother Res Aug;15(5):441-3
Kumar S, Ziereis K, Wiegrebe W, Muller K. 2000. Medicinal plants from nepal: evaluation as inhibitors of leukotriene biosynthesis. J Ethnopharmacol Jun;70(3):191-5
Navarrete A, Hong E. 1996. Anthelmintic properties of alpha-sanshool from Zanthoxylum liebmannianum. Planta Med Jun;62(3):250-1
Newall, Carol A., Linda A. Anderson and J.D. Phillipson. 1996. Herbal Medicines: A Guide for Health-Care Professionals. London: The Pharmaceutical Press.
Nissanka AP, Karunaratne V, Bandara BM, Kumar V, Nakanishi T, Nishi M, Inada A, Tillekeratne LM, Wijesundara DS, Gunatilaka AA. 2001. Antimicrobial alkaloids from Zanthoxylum tetraspermum and caudatum. Phytochemistry Apr;56(8):857-61
Osoba OA, Adesanya SA, Durosimi MA. 1989. Effect of Zanthoxylum xanthoxyloides and some substituted benzoic acids on glucose-6-phosphate and 6-phosphogluconate dehydrogenases in Hbss red blood cells. J Ethnopharmacol Nov;27(1-2):177-83
Rahman M, Alimuzzaman M, Ahmad S, Chowdhury A. 2002 Antinociceptive and antidiarrhoeal activity of Zanthoxylum rhetsa. Fitoterapia Jul;73(4):340
Shibata C, Sasaki I, Naito H, Ueno T, Matsuno S. 1999. The herbal medicine Dai-Kenchu-Tou stimulates upper gut motility through cholinergic and 5-hydroxytryptamine 3 receptors in conscious dogs. Surgery Nov;126(5):918-24
Tezuka Y, Irikawa S, Kaneko T, Banskota AH, Nagaoka T, Xiong Q, Hase K, Kadota S. 2001. Screening of Chinese herbal drug extracts for inhibitory activity on nitric oxide production and identification of an active compound of Zanthoxylum bungeanum.
 J Ethnopharmacol Oct;77(2-3):209-17
Tillotson, Alan. 2001. The One Earth Herbal Sourcebook. New York: Twin Streams/Kensington.