Medically reviewed on October 20, 2017
Scientific Name(s): Hydrastis canadensis L. Family: Ranunculaceae (buttercups)
Common Name(s): Goldenseal , yellowroot , orangeroot , eyebalm , eyeroot , goldenroot , ground raspberry , Indian turmeric , yellow puccoon , jaundice root , sceau d'or
Goldenseal may be of use in topical infections and is used as an eyewash, but clinical trials are lacking to support its effectiveness. Goldenseal has been included in cold and flu preparations for its anticatarrhal effects, but little evidence supports this use and its effects are debatable. The berberine extract of goldenseal has been used to treat diarrhea. Cardiovascular effects are not clearly defined.
Few well-controlled clinical trials are available to guide dosage. Recommended dosages vary considerably: 250 mg to 1 g 3 times daily; some product labeling suggests dosages as high as 3,420 mg/day. Ten to 30 drops of the extract 2 to 4 times a day have been recommended for influenza.
None well defined.
Documented uterine stimulant. Avoid use.
Goldenseal may affect the CYP-450 system; however, the clinical importance of this interaction is not clear.
Adverse reactions with usual doses are rare. Berberine may displace bilirubin. Very high doses of goldenseal may rarely induce nausea, anxiety, depression, seizures, or paralysis.
Research reveals little or no information regarding toxicology with the use of this product. Berberine may exhibit phototoxic ocular effects. The sodium-sparing diuretic effect of goldenseal resulted in a case report of reversible hypernatremia in a child.
Goldenseal is a perennial herb found in the rich woods of the Ohio River valley and other locations in the northeastern United States. The single, green-white flower, which has no petals, appears in the spring on a hairy stem above a basal leaf and two palmate, wrinkled leaves. The flower develops into a red-seeded berry. The plant grows from horizontal, bright yellow rhizomes, which have a twisted, knotty appearance. 1
Goldenseal root was used medicinally by American Indians of the Cherokee, Catawba, Iroquois, and Kickapoo tribes as an insect repellent, a diuretic, a stimulant, and a wash for sore or inflamed eyes. 2 It was used to treat arrow wounds and ulcers, 3 as well as to produce a yellow dye. Early settlers learned of these uses from American Indians and the root found its way into most 19th century pharmacopeias. The Eclectic medical movement was particularly enthusiastic in its adoption of goldenseal for gonorrhea and urinary tract infections. The widespread harvesting of Hydrastis in the 19th century coupled with loss of habitat, resulted in the depletion of wild populations. In 1997, Hydrastis was listed under Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora, which controls exports of the root to other countries. The final listing included roots or live plants but excluded finished products. As an alternative to wild harvesting, goldenseal is cultivated in the Skagit Valley of Washington state and is being promoted as a cash crop in New York, North Carolina, and Canada. 4 The popular notion that goldenseal can be used to affect the outcome of urinalysis for illicit drugs evolved from the novel Stringtown on the Pike by pharmacist John Uri Lloyd, in which goldenseal bitters are mistaken for strychnine in a simple alkaloid test by an expert witness in a murder trial. 5
The isoquinoline alkaloids hydrastine (4%), berberine (up to 6%), canadine, and palmatine are present in goldenseal root and are viewed as the principle bioactive components. 6 , 7 Considerable variation in alkaloid content has been noted among various commercial products available, with some not meeting the USP standards for berberine and hydrastine. 6 , 8 , 9 Some preparations contain alkaloids associated with other herbal substances. 8 , 10 Other minor alkaloids, such as canadaline and canadinic acid, 11 , 12 have been isolated. Quinic acid esters were elucidated. 13 Traces of calcium, magnesium, potassium, and zinc have been described. 14 Quantitation of the alkaloids has been accomplished in a variety of ways, including spectrophotometry, thin-layer chromatography, ion-pair dye colorimetry, high-performance liquid chromatography, capillary electrophoresis, and capillary electrophoresis-mass spectrometry. 9 , 10 , 15 , 16 , 17 , 18 , 19 , 20 , 21
Uses and Pharmacology
Despite the widespread use of goldenseal, controlled clinical trials are lacking. The alkaloids are poorly absorbed when taken orally; in vitro and animal studies must be interpreted with care. 22Antimicrobial/Antidiarrheal activity
Goldenseal alkaloids have shown modest antimicrobial activity in vitro against Staphylococcus aureus , Klebsiella and Candida species, Helicobacter pylori , and Mycobacterium tuberculosis . 13 , 23 , 24 , 25 , 26 Berberine sulfate (400 mg single dose) significantly reduced the mean stool volume after 8 hours and stopped diarrhea caused by enterotoxigenic Escherichia coli in more patients after 24 hours than the control patients. 27 Activity of berberine against diarrhea caused by cholera has been demonstrated to be minimal in comparison with tetracycline. 27 , 28Cardiovascular
Animal experiments have shown goldenseal and berberine to exhibit effects on the cardiovascular system, although the mechanisms remain poorly understood. Positive inotropic, negative chronotropic, vasodilatory, and hypotensive effects have been described. 29 , 30 , 31 The sodium-sparing diuretic effect of goldenseal resulted in a case report of reversible hypernatremia in a child. 31 Goldenseal decreased low-density lipoproteins in hyperlipidemic rats. 32 , 33 Berberine improved the lipid profile and exerted a hypoglycemic action in a small trial of patients with type 2 diabetes. 34Ophthalmic
Goldenseal has traditionally been used for eye ailments. 35 Berberine has been evaluated against sulfacetamide in ocular trachoma infections with comparable effects. 29 A phototoxic reaction leading to decreased lens epithelial cell viability between berberine alkaloid and ultraviolet A (UVA) light has been described; therefore, exercise caution until further data are available. 35 , 36Other uses
Immunostimulation has been described for berberine. 29 , 37 Berberine has been reported to inhibit uptake of glucose by cancer cells 38 and to inhibit tumor promotion by phorbol esters in a mouse skin carcinogenesis model. 39 Berberine showed weak activity in an antioxidant model. 40 , 41 Although hydrastine is closely related to the convulsant isoquinoline alkaloid bicuculline, it had no activity in a gamma-aminobutyric acid–receptor binding assay at high concentrations. 42
One study investigated the inhibitory activity of Hydrastis alkaloids on isolated rabbit aorta stimulated by epinephrine, finding a weak synergistic effect for berberine, canadine, and canadaline, but no activity with hydrastine. 43 In isolated guinea pig ileum preparations, the same group found that berberine, canadine, and canadaline evoked contractions, while hydrastine was inactive. 44 A third study found a relaxant effect of berberine on rabbit prostate strips stimulated by norepinephrine or phenylephrine 45 ; however, an adrenergic mechanism was considered unlikely. Adrenergic effects on guinea pig trachea have been described. 46
Few quality clinical trials are available to guide dosage.
Recommended dosages vary considerably: 250 mg to 1 g 3 times daily; some product labeling suggest dosages as high as 3,420 mg/day. 32 Ten to 30 drops of the extract 2 to 4 times a day have been recommended for influenza. 47
Data are inconclusive regarding the potential for drug interactions with goldenseal constituents. Studies show interaction via the CYP-450 pathway possible for at least 3 complexes (CYP2D6, CYP3A4, and CYP3A5). 47 , 51 , 52 , 53 Areas under the curve for indinavir and digoxin were decreased, but the clinical importance of this effect is unclear. 54 , 55 , 56 , 57
There has been a case report of photosensitivity with the use of a combination product containing ginseng, goldenseal, and bee pollen. 58 Very high doses of goldenseal may rarely induce nausea, anxiety, depression, seizures, or paralysis. Because of the actions of the alkaloids, exercise caution in patients being treated with cardiovascular agents.
Bibliography1. Hydrastis canadensis L. USDA, NRCS. 2007. The PLANTS Database USA. (http://plants.usda.gov, April, 2008). National Plant Data Center, Baton Rouge, LA 70874-74490
2. Hobbs C. Golden seal in early American medical botany. Pharm Hist . 1990;32(2):79-82.
3. Bolyard J. Medicinal Plants and Home Remedies of Appalachia . Springfield, IL: Charles C. Thomas; 1981.
4. Davis J. Advances in goldenseal cultivation. North Carolina Cooperative Extension Service . Horticultural Information Leaflet No. 131; 1996.
5. Foster S. Goldenseal. Hydrastis canadensis . Botanical Series, No. 309. 2nd ed. Austin, TX: American Botanical Council; 1996.
6. Weber HA, Zart MK, Hodges AE, et al. Chemical comparison of goldenseal ( Hydrastis canadensis L.) root powder from three commercial suppliers. J Agric Food Chem . 2003;51(25):7352-7358.
7. Inbaraj JJ, Kukielczak BM, Bilski P, He YY, Sik RH, Chignell CF. Photochemistry and photocytotoxicity of alkaloids from goldenseal ( Hydrastis canadensis L.). 2. Palmatine, hydrastine, canadine, and hydrastinine. Chem Res Toxicol . 2006;19(6):739-744.
8. Edwards DJ, Draper EJ. Variations in alkaloid content of herbal products containing goldenseal. J Am Pharm Assoc . 2003;43(3):419-423.
9. Govindan M, Govindan G. A convenient method for the determination of the quality of goldenseal. Fitoterapia . 2000;71(3):232-235.
10. Van Berkel GJ, Tomkins BA, Kertesz V. Thin-layer chromatography/desorption electrospray ionization mass spectrometry: investigation of goldenseal alkaloids. Anal Chem . 2007;79(7):2778-2789.
11. Genest K, Hughes DW. Natural products in Canadian pharmaceuticals. IV. Hydrastis canadensis . Can J Pharm Sci . 1969;4:41-445.
12. Galeffi C, Cometa MF, Tomassini L, Nicoletti M. Canadinic acid: an alkaloid from Hydrastis canadensis . Planta Med . 1997;63(2):194.
13. Gentry E, Jampani HB, Keshavarz-Shokri A, et al. 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. J Nat Prod . 1998;61(10):1187-1193.
14. Grippo AA, Hamilton B, Hannigan R, Gurley BJ. Metal content of ephedra-containing dietary supplements and select botanicals. Am J Health Syst Pharm . 2006;63(7):635-644.
15. Callie G, et al. Dosage spectrophotofluormetrique des alcaloides berberine, tetrahydroberberine, hydrastine et application a l'extrait sec et a la teinture d' Hydrastis canadensis L. Can J Pharm Sci . 1970;5:55.
16. Datta DD, Bose PC, Ghosh D. Thin layer chromatography and U. V. spectrophotometry of alcoholic extracts of Hydrastis canadensis . Planta Med . 1971;19(3):258-263.
17. El-Masry S, Korany MA, Abou-Donia AH. Colorimetric and spectrophotometric determinations of hydrastis alkaloids in pharmaceutical preparations. J Pharm Sci . 1980;69(5):597-598.
18. Leone M, Cometa MF, Palmery M, Saso L. HPLC determination of the major alkaloids extracted from Hydrastis canadensis L. Phytother Res . 1996;10(suppl 1):S45-S46.
19. Unger M, Stöckigt J. Improved detection of alkaloids in crude extracts applying capillary electrophoresis with field amplified sample injection. J Chromatogr A . 1997;791(1):323-331.
20. Sturm S, Stuppner H. Analysis of isoquinoline alkaloids in medicinal plants by capillary electrophoresis-mass spectrometry. Electrophoresis . 1998;19(16-17):3026-3032.
21. Abourashed EA, Khan IA. High-performance liquid chromatography determination of hydrastine and berberine in dietary supplements containing goldenseal. J Pharm Sci . 2001;90(7):817-822.
22. Yao M, Ritchie HE, Brown-Woodman PD. A reproductive screening test of goldenseal. Birth Defects Res B Dev Reprod Toxicol . 2005;74(5):399-404.
23. Scazzocchio F, Cometa MF, Palmery M. Antimicrobial activity of Hydrastis canadensis extract and its major isolated alkaloids. Fitoterapia . 1998;69:58-59.
24. Amin AH, Subbaiah TV, Abbasi KM. Berberine sulfate: antimicrobial activity, bioassay, and mode of action. Can J Microbiol . 1969;15(9):1067-1076.
25. Sun D, Courtney HS, Beachey EH. Berberine sulfate blocks adherence of Streptococcus pyogenes to epithelial cells, fibronectin, and hexadecane. Antimicrob Agents Chemother . 1988;32(9):1370-1374.
26. Mahady GB, Pendland SL, Stoia A, Chadwick LR. In vitro susceptibility of Helicobacter pylori to isoquinoline alkaloids from Sanguinaria canadensis and Hydrastis canadensis . Phytother Res . 2003;17(3):217-221.
27. Rabbani GH, Butler T, Knight J, Sanyal SC, Alam K. Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae . J Infect Dis . 1987;155(5):979-984.
28. Kin-Maung U, Myo-Khin, Nyunt-Nyunt-Wai, Aye-Kyaw, Tin-U. Clinical trial of berberine in acute watery diarrhoea. Br Med J (Clin Res Ed) . 1985;291(6509):1601-1605.
29. Berberine. Altern Med Rev . 2000;5(2):175-177.
30. Lau CW, Yao XQ, Chen ZY, Ko WH, Huang Y. Cardiovascular actions of berberine. Cardiovasc Drug Rev . 2001;19(3):234-244.
31. Bhowmick SK, Hundley OT, Rettig KR. Severe hypernatremia and hyperosmolality exacerbated by an herbal preparation in a patient with diabetic ketoacidosis. Clin Pediatr . 2007;46(9):831-834.
32. Abidi P, Chen W, Kraemer FB, Li H, Liu J. The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms. J Lipid Res . 2006;47(10):2134-2147.
33. Zhou JY, Zhou SW, Zhang KB, et al. Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats. Biol Pharm Bull . 2008;31(6):1169-1176.
34. Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism . 2008;57(5):712-717.
35. Inbaraj JJ, Kukielczak BM, Bilski P, Sandvik SL, Chignell CF. Photochemistry and photocytotoxicity of alkaloids from goldenseal ( Hydrastis canadensis L.) 1. Berberine. Chem Res Toxicol . 2001;14(11):1529-1534.
36. Chignell CF, Sik RH, Watson MA, Wielgus AR. Photochemistry and photocytotoxicity of alkaloids from goldenseal ( Hydrastis canadensis L.) 3: effect on human lens and retinal pigment epithelial cells. Photochem Photobiol . 2007;83(4):938-943.
37. Kim JS, Tanaka H, Shoyama Y. Immunoquantitative analysis for berberine and its related compounds using monoclonal antibodies in herbal medicines. Analyst . 2004;129(1):87-91.
38. Creasey WA. Biochemical effects of berberine. Biochem Pharmacol . 1979;28(7):1081-1084.
39. Nishino H, Kitagawa K, Fujiki H, Iwashima A. Berberine sulfate inhibits tumor-promoting activity of teleocidin in two-stage carcinogenesis on mouse skin. Oncology . 1986;43(2):131-134.
40. Misík V, Bezáková L, Máleková L, Kostálová D. Lipoxygenase inhibition and antioxidant properties of protoberberine and aporphine alkaloids isolated from Mahonia aquifolium . Planta Med . 1995;61(4):372-373.
41. Periera da Silva A, Rocha R, Silva CM, Mira L, Duarte MF, Florêncio MH. Antioxidants in medicinal plant extracts. A research study of the antioxidant capacity of Crataegus , Hamamelis and Hydrastis . Phytother Res . 2000;14(8):612-616.
42. Kardos J, Blaskó G, Kerekes P, Kovács I, Simonyi M. Inhibition of [3H]GABA binding to rat brain synaptic membranes by bicuculline related alkaloids. Biochem Pharmacol . 1984;33(22):3537-3545.
43. Palmery M, Cometa MF, Leone MG. Further studies of the adrenolytic activity of the major alkaloids from Hydrastis canadensis L. on isolated rabbit aorta. Phytother Res . 1996;10(suppl 1):S47-S49.
44. Commetta M, et al. Acute effect of alkaloids from Hydrastis canadensis L. on guinea pig ileum: structure-activity relationships. Phytother Res . 1996;10:S56-S58.
45. Baldazzi C, et al. Effects of the major alkaloid of Hydrastis canadensis L., berberine, on rabbit prostate strips. Phytother Res . 1998;12:589-591.
46. Abdel-Haq H, Cometa MF, Palmery M, Leone MG, Silvestrini B, Saso L. Relaxant effects of Hydrastis canadensis L. and its major alkaloids on guinea pig isolated trachea. Pharmacol Toxicol . 2000;87(5):218-222.
47. Chatterjee P, Franklin MR. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos . 2003;31(11):1391-1397.
48. Brinker FJ. Herb Contraindications and Drug Interactions . 2nd ed. Sandy, OR: Eclectic Medical Publications; 1998.
49. Newall CA, Anderson LA, Phillipson JD, eds. Herbal Medicines: A Guide for Health-Care Professionals . London: Pharmaceutical Press; 1996.
50. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG . 2002;109(3):227-235.
51. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther . 2005;77(5):415-426.
52. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine . 2003;10(4):334-342.
53. Raner GM, Cornelious S, Moulick K, Wang Y, Mortenson A, Cech NB. Effects of herbal products and their constituents on human cytochrome P450(2E1) activity. Food Chem Toxicol . 2007;45(12):2359-2365.
54. Gurley BJ, Swain A, Barone GW, et al. Effect of goldenseal ( Hydrastis canadensis ) and kava kava ( Piper methysticum ) supplementation on digoxin pharmacokinetics in humans. Drug Metab Dispos . 2007;35(2):240-245.
55. Sandhu RS, Prescilla RP, Simonelli TM, Edwards DJ. Influence of goldenseal root on the pharmacokinetics of indinavir. J Clin Pharmacol . 2003;43(11):1283-1288.
56. Mills E, Montori V, Perri D, Phillips E, Koren G. Natural health product-HIV drug interactions: a systematic review. Int J STD AIDS . 2005;16(3):181-186.
57. Lee LS, Andrade AS, Flexner C. Interactions between natural health products and antiretroviral drugs: pharmacokinetic and pharmacodynamic effects. Clin Infect Dis . 2006;43(8):1052-1059.
58. Palanisamy A, Haller C, Olson KR. Photosensitivity reaction in a woman using an herbal supplement containing ginseng, goldenseal, and bee pollen. J Toxicol Clin Toxicol . 2003;41(6):865-867.
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