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Snakeroot

Scientific Name(s): Aristolochia serpentaria L.
Common Name(s): Aristolochiae Radix, Birthwort, Caulis Aristolochiae Manshuriensis, Herba Aristolochiae Mollissima, mǎdōu líng, Pelican flower, Red River snakeroot, Sangree root, Sangrel, Snakeroot, Snakeweed, Texas snakeroot, Virginia snakeroot

Clinical Overview

Use

Despite traditional claims of efficacy for snakebite, among other uses, toxicity of Aristolochia extracts precludes their use.

Dosing

Toxicity of Aristolochia extracts precludes their use.

Contraindications

Avoid use. Aristolochia extracts are toxic. Avoid use in pregnancy.

Pregnancy/Lactation

Avoid use. Aristolochia extracts are known to be toxic. Abortifacient effects of aristolochic acids have been documented in animal studies.

Interactions

None well documented.

Adverse Reactions

Extracts of Aristolochia are known to be toxic (carcinogenic and nephrotoxic). Safety concerns regarding use of products containing aristolochic acids exist.

Toxicology

Aristolochia extracts are carcinogenic and nephrotoxic.

Botany

The genus Aristolochia (Dutchman's pipe) comprises more than 300 species of herbs and vines, including A. serpentaria (also known as Virginia snakeroot). Synonyms include Aristolochia convolvulacea, Aristolochia hastate, Aristolochia nashi, and Endodeca serpentaria. "Snakeroot" is a term also applied to the unrelated white snakeroot (Ageratina altissima), rattlesnake root (genus Prenanthes), Canadian blacksnakeroot (Sanicula canadensis), black snakeroot (Actaea racemose), and Sampson’s snakeroot (Orbexilum pedunculatum).USDA 2016

A. serpentaria is a low-growing (up to 0.6 m in height) perennial found primarily in the forests of the central and southern United States. The leaves of the plant are heart-shaped. Its exotic, brownish-purple, tube-like flowers are lined with hairs and possess a foul, fruit-like odor that attracts insects. Insects become caught in the hairs of the flowers, then become covered with pollen while struggling to escape; upon escape, the insect carries the pollen to other flowers, resulting in cross-pollination. The dried rhizome of the plant has been traditionally used as an herbal tonic for its gastric stimulant and diuretic effects.Sharp 2014

Several species of butterfly larvae feed on A. serpentaria, transferring the toxic aristolochic acids of the plant to the adult butterflies for use as a defense mechanism against predators.Pinto 2009, Wu 2000

History

Aristolochia spp. have been widely and extensively used in traditional Chinese medicine, as well as in England and the Americas. Chewed snakeroot was traditionally applied to wounds and used as a cure for snakebite by American Indians. Colonial and European physicians sometimes used snakeroot for infectious fevers, malaria, and rabies. Use in obstetrics, arthritis, eczema, cancer, and weight loss, and as an aphrodisiac, antiviral, and antibacterial agent has been recorded.Heinrich 2009, Kuo 2012, Luciano 2015, Tang 1992

Toxicity of A. serpentaria was reported as early as 1825; in 2000, the US Food and Drug Administration (FDA) issued a warning regarding preparations containing aristolochic acids.FDA 2014, Stegelmeier 2015 In 2004, the European Union ceased approving herbal preparations containing aristolochic acids. The compound has also been removed from the Pharmacopoeia of the People's Republic of China.Kuo 2012 However, products containing toxic substances such as aristolochic acids are still available, either on unregulated websites or as adulterants in other preparations.Luciano 2015

Chemistry

A. serpentaria and other members of the genus contain aristolochic acids and associated aristolactams and aporphines; protoberberine-, isoquinoline-, and benzylisoquinoline-type alkaloids; and amides, flavonoids, lignans, coumarins, terpenoids, benzenoids, and steroids. Research has focused on identifying aristolochic acids and associated chemicals because of their toxicity.Duke 1996, Kuo 2012, Michl 2014, Tang 1992

Uses and Pharmacology

Toxicity of Aristolochia preparations precludes their use.FDA 2014

Cancer

Animal data

Ethanolic root extracts of Aristolochia ringens showed inhibition of solid tumor growth (in vivo in rodents) and were significantly active in leukemia models.Akindele 2015 In vitro, activity against leukemia has been demonstrated with aristolochic acids extracted from other plants.Goun 2002

Clinical data

Research reveals no clinical data regarding the use of Aristolochia spp. in cancer; toxicity precludes use for this purpose.

Other uses

Limited studies in rodents suggest Aristolochia extracts may exert neutralizing effects against certain snake venom.Otero 2000, Shabbir 2014

Potential use of Aristolochia extracts as an insecticide, particularly against the malarial vector Anopheles stephensi, has been investigated.Pradeepa 2015

Dosing

Toxicity of Aristolochia extracts precludes their use.FDA 2014

Pregnancy / Lactation

Avoid use. Aristolochia extracts are known to be toxic. Abortifacient effects of aristolochic acids have been documented in dogs and rodentsWang 1984; the plant has been traditionally used for this purpose.Che 1984, Ganguly 1986

Interactions

None well documented. Aristolochic acids have been shown to have antithrombin activity.Goun 2002 In vitro evidence suggests that use with Panax ginseng may increase the renal toxicity of Aristolochia.Bunel 2015

Adverse Reactions

Aristolochia extracts are carcinogenic and nephrotoxic (see Toxicology section).

Toxicology

Based on case reports of nephrotoxicity, including end-stage renal disease and aristolochic acid–related DNA adducts in the renal tissue of some patients, the FDA issued a warning in 2000 regarding the nephrotoxicity and carcinogenicity of herbal products containing aristolochic acids.Duke 2002, FDA 2014 Aristolactams and 4,5-dioxoaporphine derivatives are related chemical constituents also reported to be toxic.Michl 2014

Mechanisms of action of the toxic aristolochic acids have been describedLuciano 2015, Michl 2014, Poon 2015 and associations between aristolochic acid and urothelial carcinoma made based on formation of covalent adducts with DNA, which is rarely caused by other carcinogens.Kuo 2012, Luciano 2015, Yang 2014

References

Akindele AJ, Wani Z, Mahajan G, et al. Anticancer activity of Aristolochia ringens Vahl. (Aristolochiaceae). J Tradit Complement Med. 2015;5(1):35-41.26151007
Aristolochia serpentaria. USDA, NRCS. The PLANTS Database (http://plants.usda.gov, July 2016). National Plant Data Team, Greensboro, NC 27401-4901 USA. Accessed July 2016.
Bunel V, Antoine MH, Nortier J, Duez P, Stévigny C. In vitro effects of Panax ginseng in aristolochic acid-mediated renal tubulotoxicity; apoptosis versus regeneration. Planta Med. 2015;81(5):363-372.25798640
Che CT, Ahmed MS, Kang SS, et al. Studies on Aristolochia III. Isolation and biological evaluation of constituents of Aristolochia indica roots for fertility-regulating activity. J Nat Prod. 1984;47(2):331-341.6539809
Duke J. Dr. Duke's Phytochemical and Ethnobotanical Databases. Agricultural Research Service website. http://www.ars-grin.gov/duke/. Updated June 13, 1996.
Duke J, Bogenschutz-Godwin M, duCellier J, Duke P. Handbook of Medicinal Herbs. 2nd ed. Boca Raton, FL: CRC Press; 2002.
Ganguly T, Pakrashi A, Pal AK. Disruption of pregnancy in mouse by aristolic acid: I. Plausible explanation in relation to early pregnancy events. Contraception. 1986;34(6):625-637.3829677
Goun E, Cunningham G, Solodnikov S, Krasnykch O, Miles H. Antithrombin activity of some constituents from Origanum vulgare. Fitoterapia. 2002;73(7–8):692-694.12490231
Heinrich M, Chan J, Wanke S, Neinhuis C, Simmonds MS. Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2--a global assessment based on bibliographic sources. J Ethnopharmacol. 2009;125(1):108-144.19505558
Kuo PC, Li YC, Wu TS. Chemical constituents and pharmacology of the Aristolochia (mădōu ling) species. J Tradit Complement Med. 2012;2(4):249-266.24716140
Letter to Health Professionals regarding safety concerns related to the use of botanical products containing aristolochic acid. Food and Drug Administration website. http://www.fda.gov/Food/RecallsOutbreaksEmergencies/SafetyAlertsAdvisories/ucm111200.htm. Updated June 4, 2014. Accessed January 18, 2016.
Luciano RL, Perazella MA. Aristolochic acid nephropathy: epidemiology, clinical presentation, and treatment. Drug Saf. 2015;38(1):55-64.25446374
Michl J, Ingrouille MJ, Simmonds MS, Heinrich M. Naturally occurring aristolochic acid analogues and their toxicities. Nat Prod Rep. 2014;31(5):676-693.24691743
Otero R, Núñez V, Barona J, et al. Snakebites and ethnobotany in the northwest region of Colombia. Part III: neutralization of the haemorrhagic effect of Bothrops atrox venom. J Ethnopharmacol. 2000;73(1-2):233-241.11025161
Pinto CF, Troncoso AJ, Urzúa A, Niemeyer H. Aristolochic acids affect the feeding behaviour and development of Battus polydamas archidamas larvae (Lepidoptera: Papilionidae: Troidini). Eur J Entomol. 2009;106(3):357-361.
Poon SL, Huang MN, Choo Y, et al. Mutation signatures implicate aristolochic acid in bladder cancer development. Genome Med. 2015;7(1):38.26015808
Pradeepa V, Sathish-Narayanan S, Kirubakaran SA, Thanigaivel A, Senthil-Nathan S. Toxicity of aristolochic acids isolated from Aristolochia indica Linn (Aristolochiaceae) against the malarial vector Anopheles stephensi Liston (Diptera: Culicidae). Exp Parasitol. 2015;153:8-16.25660198
Shabbir A, Shahzad M, Masci P, Gobe GC. Protective activity of medicinal plants and their isolated compounds against the toxic effects from the venom of Naja (cobra) species. J Ethnopharmacol. 2014;157:222-227.25291011
Sharp J, Whitson M. Aristolochia serpentaria. Virginia Snakeroot. Encyclopedia of Life. http://www.eol.org/. Updated 2014. Accessed Jan 18, 2016.
Stegelmeier BL, Brown AW, Welch KD. Safety concerns of herbal products and traditional Chinese herbal medicines: dehydropyrrolizidine alkaloids and aristolochic acid. J Appl Toxicol. 2015;35(12):1433-1437.26152912
Tang W, Eisenbrand G, eds. Aristolochia spp. Chinese Drugs of Plant Origin: Chemistry, Pharmacology, and Use in Traditional and Modern Medicine. Berlin: Springer; 1992:145-157.
Wang WH, Zheng JH. The pregnancy terminating effect and toxicity of an active constituent of Aristolochia mollissima Hance, aristolochic acid A. Yao Xue Xue Bao. 1984;19(6):405-409.6536147
Wu TS, Leu YL, Chan YY. Aristolochic acids as a defensive substance for the aristolochiaceous plant-feeding swallowtail butterfly, Pachilopta aristolochiae interpositus. J Chin Chem Soc (Taipei). 2000;47(1):221-226.
Yang HY, Chen PC, Wang JD. Chinese herbs containing aristolochic acid associated with renal failure and urothelial carcinoma: a review from epidemiologic observations to causal inference. Biomed Res Int. 2014;2014:569325.25431765

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This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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