Goldenseal

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Goldenseal
Conservation status

Apparently Secure (NatureServe)[1]
Scientific classification
Kingdom: Plantae
(unranked): Angiosperms
(unranked): Eudicots
Order: Ranunculales
Family: Ranunculaceae
Genus: Hydrastis
Species: H. canadensis
Binomial name
Hydrastis canadensis
L.

Goldenseal (Hydrastis canadensis), also called orangeroot[2] or yellow puccoon,[2] is a perennial herb in the buttercup family Ranunculaceae, native to southeastern Canada and the northeastern United States. It may be distinguished by its thick, yellow knotted rootstock. The stem is purplish and hairy above ground and yellow below ground where it connects to the yellow rhizome. The plant bears two palmate, hairy leaves with 5–7 double-toothed lobes and single, small, inconspicuous flowers with greenish white stamens in the late spring. It bears a single berry like a large raspberry with 10–30 seeds in the summer.[3]

Goldenseal has been ascribed[according to whom?] the following herbal properties (whole herb): bitter, hepatic, alterative, anticatarrhal, anti-inflammatory, antimicrobial, laxative, emmenagogue, and oxytocic.[4]

Goldenseal is often used as a multi-purpose remedy, and is thought[according to whom?] to possess many different medicinal properties. In addition to being used as a topical antimicrobial, it is also taken internally as a digestion aid.[citation needed] Goldenseal may be purchased in salve, tablet, tincture form, or as a bulk powder. Goldenseal is often used to boost the medicinal effects of other herbs with which it is blended or formulated.

A second species from Japan, previously listed as Hydrastis palmatum, is sufficiently distinct that it is now usually treated in a separate genus, as Glaucidium palmatum.

Efficacy[edit]

There is currently insufficient evidence to determine whether goldenseal is effective for any conditions.[5][6][7] According to the American Cancer Society, "evidence does not support claims that goldenseal is effective in treating cancer or other diseases. Goldenseal can have toxic side effects, and high doses can cause death."[8]

Traditional usage[edit]

Goldenseal in flower

At the time of the European colonization of the Americas, goldenseal was in extensive use among certain Native American tribes of North America, both as a medicine and as a coloring material. Prof. Benjamin Smith Barton in his first edition of Collections for an Essay Toward a Materia Medica of the United States (1798), refers to the Cherokee use of goldenseal as a cancer treatment. Later, he calls attention to its properties as a bitter tonic, and as a local wash for ophthalmia. It became a favorite of the Eclectics from the time of Constantine Raffinesque in the 1830s.

Herbalists today consider goldenseal an alterative, anti-catarrhal, anti-inflammatory, antiseptic, astringent, bitter tonic, laxative, anti-diabetic and muscular stimulant. They discuss the astringent effect it has[citation needed] on mucous membranes of the upper respiratory tract, the gastrointestinal tract, the bladder, and rectum (applied topically), and the skin. Goldenseal is very bitter, which stimulates the appetite and aids digestion, and often stimulates bile secretion.[9][10][unreliable source?][11][12]

Mechanism of action[edit]

Herbalist Paul Bergner investigated the research and has been unable to find case reports where the level of intestinal pathogens are lower after taking goldenseal.[13] In fact, a study by Rabbani[14] where men with E. coli induced diarrhea had 42–48% reduced symptoms after taking berberine showed unchanged levels of intestinal bacteria, pathogenic or otherwise.

It appears likely that goldenseal shares with Mahonia (Oregon grape) and Berberis (Barberry) the ability to inhibit the drug resistance efflux pumps (MDR pumps) of bacteria, as discussed below.

Constituents and modern pharmacology[edit]

Goldenseal contains the isoquinoline alkaloids: hydrastine, berberine, berberastine, hydrastinine, tetrahydroberberastine, canadine, and canalidine.[15] A related compound, 8-oxotetrahydrothalifendine was identified in one study.[16] One study analyzed the hydrastine and berberine contents of twenty commercial goldenseal and goldenseal-containing products and found they contained variously 0%-2.93% hydrastine and 0.82%-5.86% berberine.[17] Berberine and hydrastine act as quaternary bases and are poorly soluble in water but freely soluble in alcohol. The herb seems to have synergistic antibacterial activity over berberine in vitro, possibly due to efflux pump inhibitory activity.[18]

Multiple bacteria and fungi, along with selected protozoa and chlamydia are susceptible to berberine in vitro.[19] Berberine alone has weak antibiotic activity in vitro since many microorganisms actively export it from the cell (although a whole herb is likely to work on the immune system as well as on attacking the microbes and hence have a stronger clinical effect than the antibiotic activity alone would suggest).[citation needed] Interestingly, there is some evidence for other berberine-containing species synthesizing an efflux pump inhibitor that tends to prevent antibiotic resistance, a case of solid scientific evidence that the herb is superior to the isolated active principle.[20] However, it is not yet known whether goldenseal contains a drug resistance efflux pump inhibitor, although many antimicrobial herbs do.[citation needed]

Toxicity[edit]

Most of the research that is popularly attributed to goldenseal has actually been into the constituent berberine, which goldenseal has in common with a variety of other medicines including oregon-grape, coptis, phellodendron, barberry (Berberis vulgaris) and yellowroot. However, constituents frequently act differently in isolation than a whole herb acts in the body. In 1996, the committee of the European Union that regulates drugs placed barberry in a table of Herbal Drugs with Serious Risks without any Accepted Benefit because it contains berberine.[citation needed] Paul Bergner investigated the literature and was able to find only a single report of potential adverse effects of berberis species, berberine-containing plants, or berberine itself in a computer search of the MEDLINE and TOXLINE databases of the U.S. National Library of Medicine. This was a study in China that showed that berberine sulfate is inappropriate for the treatment of newborn infants with prenatal jaundice.[21] However that is not a likely scenario in a country where babies born jaundiced are hospitalized, but it does lend credence to the traditional advice not to take goldenseal or other berberine herbs during pregnancy.[22]

Research into the toxicology and pharmacology of goldenseal has focused on berberine and hydrastine, which are antimicrobial, chloretic and each have a variety of other properties helping immunity. But toxicity in a concentrated constituent does not translate to toxicity of the whole herb, which contains many other compounds. In one study, the lethal dose (LD50) for rats was 12 times lower with hydrastine than with goldenseal extract.[23][24]

A study where pregnant rats fed were about 47 times the usual human dose of 26 mg/kg concluded, "Maternal liver weights were increased at ≥6250 ppm, suggesting possible enzyme induction. There was no definitive evidence of developmental toxicity in this study."[25] Another study, where mice were fed ~300 times the estimated human intake from dietary supplements, concluded, "Maternal liver weights were increased at greater than 12,500 ppm, but in the absence of treatment-related histopathological lesions. At the high dose, definitive evidence of developmental toxicity was limited to a statistically significant (~8%) reduction in average fetal body weight per litter."[26]

The lethal dose (LD50) of berberine isolates in humans is thought to be 27.5 mg/kg. Berberine is absorbed slowly orally; it achieves peak concentrations in 4 hours and takes 8 hours to clear[27] Berberine is excreted in the urine and human studies of berberine show evidence it can be absorbed through the skin. Pharmacokinetic data is not available for hydrastine or goldenseal root powder. Berberine in humans can cause blocking of receptors in smooth muscle, blocking potassium channels in the heart and reducing ventricular tachycardia, inhibiting intestinal ion secretion and toxin formation in the gut and increasing bile secretion.[28]

While goldenseal, like all alkaloid-rich herbs including coffee and tobacco should be avoided during pregnancy and given to very young children with care, it appears that goldenseal is unlikely to be toxic in normal doses. Interactions with drugs with narrow therapeutic windows like warfarin, ciclosporin, protease inhibitors and cardiac glycosides are potential concerns.

Side effects of goldenseal may include "digestive complaints, nervousness, depression, constipation, rapid heartbeat, diarrhea, stomach cramps and pain, mouth ulcers, nausea, seizures, vomiting, and central nervous system depression. High doses may cause breathing problems, paralysis, and even death. Long-term use may lead to vitamin B deficiency, hallucinations, and delirium."[8] In addition, goldenseal may cause brain damage to newborn babies if given to them directly or if taken by their breastfeeding or pregnant mothers,[5] and may affect blood pressure unpredictably because it contains several different compounds that have opposite effects on blood pressure.[8]

Cautions[edit]

Goldenseal has an affinity for mucosa, and is cooling so should not be used if an infection is at an early stage or there are more chills than fever.[citation needed] Goldenseal should be used with caution only while sick with illnesses that respond to hydrastine and berberine. It should generally not be taken for an early stage Upper Respiratory Infection (URI), but reserved for illnesses in which there is yellow or green phlegm.[citation needed] Generally a two-week maximum dosage is suggested.[citation needed] Taking goldenseal over a long period of time can reduce absorption of B vitamins. Avoid goldenseal during pregnancy and lactation, with gastrointestinal inflammation, and with proinflammatory disorders.[12] A recent study (2011) found rats fed with Goldenseal constantly for two years had a greater tendency towards tumor formation.[29]

Goldenseal has been found to have inhibited cytochrome P450 CYP2D6, CYP3A4, and CYP3A5 activity by approximately 40%, a statistically and clinically significant reduction.[30] CYP2D6 specifically is a known metabolizer of many commonly used pharmaceuticals, such as antidepressants (including all SSRIs except for fluvoxamine), neuroleptics, and codeine.[31] Combining Goldenseal with such medications should be done with caution and under the supervision of a doctor as it can lead to serious - perhaps fatal - toxicity.[32] Those with a genetic deficiency in these enzymes are at particular risk.

Use for masking illicit drug use in urine drug tests[edit]

Goldenseal became a part of American folklore associated with chemical testing errors, from pharmacist John Uri Lloyd's 1900 novel Stringtown on the Pike. In the book, the victim's habit of taking goldenseal in the form of digestive bitters, causes this herb to appear as the poison strychnine in a chemical test - thus suggesting murder. It has been used on occasions in this century to attempt to mask the use of morphine in race horses (without success).[33]

Two studies have demonstrated no effect of oral goldenseal on urine drug assays over water alone.[34] Subjects who drank large amounts of water had the same urine drug levels as subjects who took goldenseal capsules along with the water.

Endangered status[edit]

Goldenseal became popular in the mid-nineteenth century. By 1905, the herb was much less plentiful, partially due to overharvesting and partially to habitat destruction. Wild goldenseal is listed in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES),[35] which by definition means harvest from public land is prohibited and may require a permit to export, although trade of the plants is still deemed to be undetrimental to the wildlife population and is otherwise unregulated. More than 60 million goldenseal plants are picked each year without being replaced.[36] The process of mountain top removal mining has recently put the wild goldenseal population at major risk due to loss of habitat, illegality of removing goldenseal for transplant without registration while destruction in the process of removing the mountain top is permitted, and increased economic pressure on stands outside of the removal area.[37]

Many herbalists urge caution in choosing products containing goldenseal, as they may have been harvested in an unsustainable manner as opposed to having been organically cultivated.[citation needed]

There are several berberine-containing plants that can serve as useful alternatives, including Chinese coptis, yellowroot, or Oregon grape root.[38]

See also[edit]

References[edit]

  1. ^ "Hydrastis canadensis". NatureServe Explorer. NatureServe. Retrieved 2007-03-20. 
  2. ^ a b "USDA GRIN Taxonomy". 
  3. ^ Foster S. and Duke J. (2000): A Field guide to Medicinal Plants and Herbs of Eastern and Central North America. New York, Houghton Mifflin
  4. ^ Hoffman David (2003): Medical Herbalism. Rochester, Vermont, Healing Arts Press
  5. ^ a b Goldenseal, WebMD.
  6. ^ Goldenseal, NCCAM.
  7. ^ Goldenseal, NYU Langone Medical Center.
  8. ^ a b c Goldenseal, American Cancer Society.
  9. ^ Tierra Michael (1998): The Way of Herbs. New York, Pocket Books
  10. ^ Grieve M. (1971): A Modern Herbal. New York, Dover Publications, Inc
  11. ^ Mills S. and Bone K. (2000): Principles and Practice of Phytotherapy. Philadelphia, Churchill Livingstone
  12. ^ a b http://www.med.unc.edu/phyrehab/ncmedicinalherbs/goldenseal/Goldenseal-hp.pdf
  13. ^ [1] Bergner, Paul Goldenseal and the Antibiotic Myth Medical Herbalism: A Journal for the Clinical Practitioner Volume 8, Number 4, Winter 1996–1997
  14. ^ Rabbani GH, Butler T, Knight J, Sanyal SC, Alam K (May 1987). "Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae". The Journal of Infectious Diseases 155 (5): 979–84. doi:10.1093/infdis/155.5.979. PMID 3549923. 
  15. ^ Weber HA, Zart MK, Hodges AE, et al. (December 2003). "Chemical comparison of goldenseal (Hydrastis canadensis L.) root powder from three commercial suppliers". Journal of Agricultural and Food Chemistry 51 (25): 7352–8. doi:10.1021/jf034339r. PMID 14640583. 
  16. ^ Gentry EJ, Jampani HB, Keshavarz-Shokri A, et al. (October 1998). "Antitubercular natural products: berberine from the roots of commercial Hydrastis canadensis powder. Isolation of inactive 8-oxotetrahydrothalifendine, canadine, beta-hydrastine, and two new quinic acid esters, hycandinic acid esters-1 and -2". Journal of Natural Products 61 (10): 1187–93. doi:10.1021/np9701889. PMID 9784149. 
  17. ^ Edwards DJ, Draper EJ, Variations in alkaloid content of herbal products containing goldenseal, J Am Pharm Assoc (2003). 2003 May-Jun;43(3):419-23.
  18. ^ Ettefagh K.A., Burns J.T., Junio H.A., Kaatz G.W., Cech N.B., "Goldenseal (Hydrastis canadensis L.) Extracts Synergistically Enhance the Antibacterial Activity of Berberine via Efflux Pump Inhibition", Planta Medica 2010
  19. ^ Mills, Simon; Bone, Kerry (2000). Principles and practice of phytotherapy: modern herbal medicine. Edinburgh: Churchill Livingstone. ISBN 978-0-443-06016-8. [page needed]
  20. ^ Lewis K (April 2001). "In search of natural substrates and inhibitors of MDR pumps". Journal of Molecular Microbiology and Biotechnology 3 (2): 247–54. PMID 11321580. 
  21. ^ Chan E (1993). "Displacement of bilirubin from albumin by berberine". Biology of the Neonate 63 (4): 201–8. doi:10.1159/000243932. PMID 8513024. 
  22. ^ [2] Bergner, Paul Goldenseal Substitutes Medical Herbalism: A Journal for the Clinical Practitioner Volume 8, Number 4, Winter 1996–1997
  23. ^ Tice Raymond (1997): Goldenseal and two of its constituent alkaloids: berberine and hydrastine Research Triangle Park, National Institute of Environmental Health Sciences, in Seiger E: Review of Toxilogical Literature.
  24. ^ Mills Simon and Bone Kerry (2000): Principles and Practice of Phytotherapy. Philadelphia, Churchill Livingstone.
  25. ^ (2003): Developmental Toxicity Evaluation for Goldenseal Root Powder (Hydrastis Canadensis) Administered in the Feed to Sprague-Dawley (CD) Rats on Gestational Days 6 to 20 Research Triangle Park, NC: National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health
  26. ^ Developmental Toxicity Evaluation for Goldenseal (Hydrastis canadensis) Root Powder Administered in the Feed to Swiss (CD-1) Mice on Gestational Days 6-17
  27. ^ Jellin J.M., Gregory P.J., Batz F. and Hitchens K. (2004): Pharmacist's Letter/ Prescriber's Letter Natural Medicines Comprehensive Database. Stockton, CA, Therapeutic Research Faculty. Accessed: 1/12/2004, http://www.naturaldatabase.com/member_home.asp?ph_img=memberhome.gif&ex=0&ex=0
  28. ^ Mills Simon and Bone Kerry (2000): Principles and Practice of Phytotherapy. Philadelphia, Churchill Livingstone.
  29. ^ Dunnick JK, "Investigating the Potential for Toxicity from Long-Term Use of the Herbal Products, Goldenseal and Milk Thistle." Toxicol Pathol. 2011 Feb 7;
  30. ^ http://www.ncbi.nlm.nih.gov/pubmed/15900287?dopt=Abstract
  31. ^ http://www.fass.se/LIF/produktfakta/fakta_lakare_artikel.jsp?articleID=18352
  32. ^ http://www.mendeley.com/research/fatal-intoxication-cases-cytochrome-p450-2d6-and-2c19-genotype-distributions/
  33. ^ Black Cohosh, Cimicifuga racemosa, Actaea racemosa, article and photos by Steven Foster
  34. ^ Jellin J.M., Gregory P.J., Batz F. and Hitchens K. (2004): Pharmacist's Letter/ Prescriber's Letter Natural Medicines Comprehensive Database. Stockton, CA, Therapeutic Research Faculty. http://www.naturaldatabase.com/member_home.asp?ph_img=memberhome.gif&ex=0&ex=0
  35. ^ Foster Steven and Tyler Varro E. (1999): Tyler's Honest Herbal: A sensible guide to the use of herbs and related remedies. Binghamton, NY, The Haworth Herbal Press
  36. ^ Dworkin, Norine (1999). "Where Have All the Flowers Gone? - herbal supplements threaten some herb species". Vegetarian Times. 
  37. ^ http://cms.herbalgram.org/herbalgram/issue73/article3080.html?ts=1390375664&signature=31b6c6d2eaf40423702e4e49661ce6db Dean Myles Saving Wild Ginseng, Goldenseal, and other Native Plants from Mountain Top Removal. HerbalGram. 2007;73:50 © American Botanical Council
  38. ^ Bergner, Paul. The Healing Powers of Echinacea, Goldenseal and Other Immune System Herbs. Prima 1997 ISBN 978-0-7615-0809-0

Literature[edit]

External links[edit]