Goldenseal

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

Uses

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.

Dosing

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.

Contraindications

None well defined.

Pregnancy/Lactation

Documented uterine stimulant. Avoid use.

Interactions

Goldenseal may affect the CYP-450 system; however, the clinical importance of this interaction is not clear.

Adverse Reactions

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.

Toxicology

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.

Botany

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

History

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

Chemistry

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. 22

Antimicrobial/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 , 28

Cardiovascular

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. 34

Ophthalmic

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 , 36

Other 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

Dosage

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

Pregnancy/Lactation

Documented uterine stimulant. Avoid use. 11 , 29 , 48 , 49 , 50 Berberine may displace bilirubin and should not be used in jaundiced infants. 29

Interactions

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

Adverse Reactions

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.

Toxicology

Research reveals little or no information regarding toxicology. A phototoxic reaction between berberine alkaloid and UVA light has been described. 35 , 36

Bibliography

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