Goldenseal

Goldenseal (Hydrastis canadensis L.)

1. Identity and Botanical Description

Botanical and Chemical Names

Botanical name: Hydrastis canadensis L. Also called orangeroot or yellow puccoon, goldenseal is a perennial herb in the buttercup family Ranunculaceae, native to North America. Additional synonyms and common names include eyebalm, eyeroot, hydrastis, orangeroot, turmeric root, and yellowroot.

Plant Morphology and Natural Habitat

A member of the Ranunculaceae family, H. canadensis is native to North America, with a natural range from southern Quebec to northern Georgia and west to Missouri. It is an herbaceous perennial found growing naturally in rich, densely shaded, deciduous forests. The plant emerges in early spring from buds that overwinter on the perennial rootstock, growing each year to a height of 8 to 14 inches. The dark-green leaf is palmate-shaped with a long petiole and can have five to seven lobes, with double-serrated margins. A single greenish-white flower blooms briefly from late April to May depending upon location; a single green berry-like fruit develops, turning red in July and containing up to 30 black seeds.

The plant 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. It is berberine that gives the rootstock its distinctive golden color. Each fall its leaves and stem die back, leaving a cup-like scar on the perennial rhizome that looks like an old wax seal, which is the origin of the name "goldenseal."

Medicinal Plant Part

The rhizome and fibrous roots constitute the primary medicinal parts used. Goldenseal roots (rather than aerial portions) are more commonly employed medicinally because of their higher alkaloid content.

Common Dosage Forms and Preparations

Goldenseal is available in liquid, tablet, and capsule forms standardized to the active components. It is commonly consumed in capsules, liquid herbal extracts, and as an herbal tea. Various preparations are used as an antiseptic wash for mouth sores, inflamed and sore eyes, and irritated skin and as a douche for vaginal infections. It has been combined with echinacea as a cold remedy. Goldenseal supplements are available in a wide range of forms, including capsules, lotions, drops, sprays, eyewashes, and feminine hygiene products.

2. Traditional and Historical Use

Native American Use

Goldenseal is a medicinal plant widely used in various traditional systems of medicine. It has been traditionally used by Native Americans as a coloring agent and as a medicinal remedy for common diseases and conditions including wounds, digestive disorders, ulcers, skin and eye ailments, and cancer.

Goldenseal was traditionally used by Native Americans as a medicinal remedy and as a colouring agent. In his Collections for an Essay Towards a Materia Medica of the United States, the American botanist Benjamin Smith Barton first mentioned the medicinal use of H. canadensis by the Cherokee.

Native Americans of the Cherokee, Catawba, Iroquois, and Kickapoo tribes used goldenseal root as an insect repellent, diuretic, stimulant, and wash for sore or inflamed eyes. It was used to treat arrow wounds and ulcers, as well as to produce yellow dye. The Cherokees also used it as a wash to treat skin diseases and sore eyes, and mixed a powder made from the root with bear fat for use as an insect repellent.

Iroquois medicine practitioners prepared infusions of the root for treating ear infections, liver ailments, and stomach troubles. They also used it as a wash for sore eyes, a practice that would persist for centuries among both indigenous and settler communities. Other tribes, including the Micmac, Chippewa, and Potawatomi, incorporated goldenseal into their pharmacopeias for treating ulcers, gonorrhea, arrow wounds, and cancerous growths.

Adoption by European Settlers and 19th-Century Eclectic Medicine

European settlers quickly adopted the herb after witnessing its uses, and by the early 19th century goldenseal became a staple in Eclectic Medicine — a popular American herbal tradition that blended Native American remedies with European botanical knowledge. Early settlers learned of these uses from Native Americans, and the root found its way into most 19th-century pharmacopeias.

In 1830, physician John King listed Hydrastis canadensis in his American Dispensatory, praising its use for "dyspeptic complaints" and gum and mouth ailments. By the late 1800s, German physician J. U. Lloyd investigated goldenseal's chemical profile and identified the signature alkaloid berberine. Around the same time, the Eclectics and Physiomedicalists recommended it for jaundice, diarrhea, and eye conditions.

The United States Pharmacopoeia required Hydrastis to yield not less than 2.5 percent of hydrastine. Goldenseal eyewashes remained in the United States Pharmacopeia until the mid-20th century.

Scope of Traditional Applications

Today, the main applications of H. canadensis are for the prevention and treatment of skin disorders, dyspepsia, gastritis, peptic ulcer, colitis, anorexia, menorrhagia, dysmenorrhoea, sinusitis, mucosal inflammation, and other inflammatory conditions or infectious diseases. Goldenseal powder has an astringent effect on the mucous membranes of the upper respiratory tract, the gastrointestinal tract, the bladder, the rectum, and the skin; astringent herbs have been used to reduce blood loss from the reproductive tract as well as the gastrointestinal tract, respiratory tract, and skin.

3. Key Constituents and Active Compounds

Principal Alkaloids

Goldenseal contains the isoquinoline alkaloids hydrastine, berberine, berberastine, hydrastinine, tetrahydroberberastine, canadine, and canalidine. The main constituents of the goldenseal root are isoquinoline alkaloids, such as hydrastine (1.5–4%), berberine (2.5%), canadine (0.5%), and other alkaloids. Berberine is usually found in goldenseal roots as a sulphate at a concentration of 5,000–60,000 ppm. Hydrastine is also found in goldenseal in concentrations of 15,000–40,000 ppm. Secondary metabolites include sideroxylin, 8-desmethyl-sideroxylin, and 6-desmethyl-sideroxylin.

Berberine

Berberine is one of the most bioactive alkaloids identified in different parts of goldenseal. Although at least 10 isoquinoline alkaloids have been identified in goldenseal, berberine is considered the primary pharmacologically active compound. Berberine's most common historic and clinical uses include bacterial diarrhea, intestinal parasites, and ocular trachoma infections. Berberine has been shown to exhibit significant antimicrobial activity against a variety of bacteria, fungi, protozoans, helminths, chlamydia, and viruses.

Hydrastine

Hydrastine is commercially available in the form of (–)-hydrastine and has been used as an ingredient in some decongestant nose sprays and feminine hygiene products. Hydrastine, one of goldenseal's major alkaloids, has vasoconstrictive properties and can raise blood pressure.

Synergy Among Constituents

Some berberine-containing plants have been shown to produce substances which, by themselves, are completely without antimicrobial activity; however, when used in conjunction with berberine, they enhanced the activity of berberine by as much as 2,500 times. Synergistic antibacterial activity was observed between the aerial extract (FIC 0.375) and to a lesser extent the root extract (FIC 0.750) and berberine in published PMC research. Results show that when extracts are standardized to berberine content, extracts from the aerial portions of the plants synergize the antimicrobial activity of berberine. This finding indicates that some constituent(s) other than berberine in H. canadensis aerial portions synergistically enhance the antimicrobial activity of berberine.

4. Mechanisms of Action

Antimicrobial Activity

Berberine demonstrates broad-spectrum antibacterial activity against both gram-positive and gram-negative bacteria. Its mechanism of action is multifaceted, targeting bacterial DNA synthesis, protein production, and cell membrane integrity simultaneously.

A key mechanism involves efflux pump inhibition. Research has shown that canadine potently inhibits the NorA efflux pump in staphylococcal species, reducing the minimum inhibitory concentration (MIC) of berberine by 4- to 16-fold when the two compounds are combined. This synergy between alkaloids is considered significant in the plant's overall antimicrobial profile.

Antiviral Mechanisms

Studies of the mechanism underlying berberine's antiviral effect suggest that berberine acts post-translationally to inhibit virus protein trafficking/maturation, which in turn inhibits virus growth. Berberine was also evaluated for its ability to inhibit production of TNF-α and PGE₂ from influenza A-infected cells, with strong inhibition of production of both inflammatory mediators observed.

Anti-inflammatory Mechanisms

The goldenseal extract containing berberine has showed numerous therapeutic effects including antimicrobial, anti-inflammatory, hypolipidemic, hypoglycemic, antioxidant, neuroprotective, cardioprotective, and gastrointestinal protective activity in preclinical studies.

Cardiovascular Effects of Berberine

In humans, berberine has positive inotropic, negative chronotropic, antidysrhythmic, and vasodilator properties. There is experimental evidence that berberine can cause arterial hypotension.

Cytochrome P450 Inhibition

Major constituents of goldenseal include the isoquinoline alkaloids berberine, hydrastine, and hydrastinine. These constituents contain a methylenedioxyphenyl ring, a structural alert that can lead to irreversible inhibition of drug metabolizing enzymes, particularly the cytochromes P450 (CYPs).

5. Scientific Evidence by Area of Use

5.1 Overall Evidence Summary

According to the NCCIH (National Center for Complementary and Integrative Health), there is not enough evidence to determine whether goldenseal is useful for any health conditions. More research would be needed before any conclusions can be reached. No rigorous studies have been done to evaluate the effects of goldenseal on health conditions in people. Goldenseal is one of the top 20-selling herbs in the United States, in spite of the fact that no clinical trials have been conducted to assess any use of this North American indigenous plant.

A critical caveat applies to the interpretation of much of the available research: Berberine, a substance found in goldenseal, has been studied for its effects on blood sugar, blood cholesterol levels, body weight, and other health-related outcomes. However, when people take goldenseal orally, very little berberine may be absorbed by the body, so study results on berberine may not apply to goldenseal.

5.2 Antimicrobial / Infectious Disease

In vitro and preclinical evidence: In test tube studies, goldenseal has shown a wide spectrum of antibiotic activity against disease-causing organisms, such as Chlamydia, E. coli, Salmonella typhi, and Entamoeba histolytica. Among several herbs tested in vitro, goldenseal extract was the most active growth inhibitor of H. pylori. Research from 2010 shows goldenseal extracts may kill C. jejuni, a bacterium responsible for gastroenteritis that causes diarrhea and vomiting.

Limitations: Studies on goldenseal and its compounds are limited. The effect of goldenseal in the gastrointestinal tract is most likely localized, as its alkaloids (particularly berberine) are poorly absorbed into the bloodstream, limiting any systemic antibiotic effects.

5.3 Upper Respiratory Tract Infections and the Common Cold

Goldenseal is currently promoted as a dietary supplement for the common cold and other upper respiratory tract infections, hay fever, diarrhea, constipation, and other conditions. Goldenseal is one of the most popular herbs in the United States, often combined with echinacea and sold to treat or prevent colds — but there is no evidence that it works. There are currently no RCTs evaluating the efficacy of goldenseal, either alone or in combination with echinacea.

5.4 Gastrointestinal Health and Diarrhea

Human trials have used isolated berberine to treat diarrhea and gastroenteritis with good results; however, the whole root has not been clinically studied. Berberine's most common historic and clinical uses include bacterial diarrhea and intestinal parasites. The critical distinction is that these studies used purified, isolated berberine — not whole goldenseal preparations — and the extrapolation to goldenseal supplements is not established by clinical evidence.

5.5 Blood Glucose and Metabolic Effects

Berberine, a substance found in goldenseal, has been studied for its effects on blood sugar, blood cholesterol levels, body weight, and other health-related outcomes. Both human and animal studies have found that berberine in goldenseal may help lower LDL cholesterol and triglyceride levels. A 2018 review of animal studies and a 2017 review including human studies found that berberine may help reduce LDL cholesterol and triglyceride levels. Again, however, these findings pertain to isolated berberine rather than whole goldenseal, and the bioavailability caveat described above applies.

5.6 Eye Infections (Conjunctivitis)

Native American tribes, particularly the Cherokee and Iroquois, used goldenseal root decoctions as an eyewash for conjunctivitis, blepharitis, and other ocular inflammations. This practice was adopted by Eclectic physicians in the 19th century, and goldenseal eyewashes remained in the United States Pharmacopeia until the mid-20th century. Berberine has demonstrated in vitro activity against common conjunctivitis-causing organisms, including Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa. Clinical human trials on goldenseal eyewash preparations specifically are lacking.

5.7 MRSA and Efflux Pump Inhibition

Goldenseal is used to combat inflammation and infection; its antibacterial activity in vitro has been attributed to its alkaloids, the most abundant of which is berberine. In vitro research published on PMC demonstrated that goldenseal roots have higher alkaloid content than aerial portions, but when extracts are standardized to berberine content, extracts from the aerial portions synergize the antimicrobial activity of berberine. This research is in vitro only; no human clinical trials have examined goldenseal for MRSA specifically.

5.8 Immune Stimulation

Only one study found that goldenseal might help boost white blood cells (a measure of the infection-fighting ability of the immune system), and the study was not well designed. Evidence in this area is therefore insufficient to draw conclusions.

5.9 Drug Test Masking (A Popular Claim)

Goldenseal has also been used to mask illicit drugs in the urine, although it appears to be ineffective with modern laboratory methods. Several studies have reported that taking goldenseal does not change the results of a drug test.

6. Body Systems and Health Areas of Association

• Gastrointestinal system: The rhizome of this plant has been used for the treatment of a variety of diseases including gastrointestinal disorders, ulcers, muscular debility, nervous prostration, and constipation.
• Mucous membranes (respiratory, digestive, urinary): Goldenseal was used by Native Americans as a treatment for irritations and inflammation of the mucous membranes of the respiratory, digestive, and urinary tracts.
• Skin: Lab studies indicate that goldenseal compounds have antimicrobial properties, but also suggest potential sensitivity to sunlight with topical products that contain goldenseal.
• Cardiovascular system: In humans, berberine has positive inotropic, negative chronotropic, antidysrhythmic, and vasodilator properties.
• Ocular system: Goldenseal was commonly used topically for skin and eye infections and has been used historically as a mouthwash to help heal canker sores.
• Reproductive / gynecological: Goldenseal has been used as a tonic, antiperiodic, diuretic, and as a vaginal douche.
• Musculoskeletal: Lab studies suggest goldenseal may relax muscle tissue, but human data are lacking.

7. Dosage Forms and Reported Dosages

As a dietary supplement, goldenseal can be given at a wide range of doses: decoction of dried roots, 0.5–10 g three times per day; alcoholic tincture, 2–4 mL three times per day; and fluid extract, 0.3–10 mL three times per day.

OTC preparations of goldenseal are available in doses of 100 mg up to 470 mg. Powdered goldenseal root and rhizome, 4–6 grams per day in tablet or capsule form, is sometimes recommended. Alternatively, 250–500 mg three times per day of standardized extracts supplying 8–12% alkaloids are suggested.

Regarding standardized extracts specifically, standardized root extracts of goldenseal are generally dosed in a range of 50 mg/day to 300 mg/day, with higher amounts administered in divided doses. For example, 100 mg three times daily may be used; another common approach to dosing goldenseal would be 150 mg twice daily.

In the clinical pharmacokinetic studies of CYP inhibition, a goldenseal extract (900 mg) administered three times daily for 28 days was used, which inhibited CYP2D6 and CYP3A activity by approximately 40%. In a separate study examining transporter effects, goldenseal root (1,140 mg twice daily for 14 days) had no effect on the pharmacokinetics of a single oral dose of indinavir 800 mg.

No studies can currently confirm whether any particular dosage is the most beneficial.

8. Safety Considerations and Drug Interactions

CYP450 Drug Interactions — Clinically Documented

Goldenseal appears to inhibit some cytochrome P450 (CYP) drug-metabolizing isozymes, specifically CYP3A4, CYP2D6, and probably CYP2C9. Botanical supplements containing goldenseal strongly inhibited CYP2D6 and CYP3A4/5 activity in vivo in a controlled human study involving 12 healthy volunteers who were randomly assigned to receive goldenseal for 28 days, with CYP activity measured via probe drug cocktails before and after supplementation.

Clinical studies involving healthy volunteers demonstrated that, compared to baseline, CYP2D6 and CYP3A activities were reduced by 40–60% following administration of approximately 1 g of a goldenseal extract three times daily for 14 or 28 days.

Because CYP3A4 metabolizes more drugs than any other isozyme, there is a potential for numerous interactions with goldenseal. Serious adverse interactions may result from the concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 and CYP3A4/5 substrates. Some drugs such as codeine and tamoxifen are administered as prodrugs, and CYP2D6 is required for their activation. Thus, goldenseal would theoretically reduce the efficacy of such medications.

In addition to CYP enzymes, in vitro studies using a goldenseal extract standardized to berberine predicted the extract would also inhibit the efflux transporter breast cancer resistance protein (BCRP) and uptake transporters organic anion transporting polypeptide (OATP) 1B1/3.

Effect on Metformin

A study funded by NCCIH found that levels of metformin decreased about 25 percent in healthy adults who were given goldenseal extract plus metformin. This drop was enough to potentially hinder glucose control in people with type 2 diabetes taking metformin.

Effect on Anticoagulants

Goldenseal may interact with warfarin, and berberine may enhance the anticoagulant effect of heparin.

Adverse Effects

Goldenseal can have many adverse effects, including nausea, anxiety, dyspepsia, uterine contractions, and jaundice in neonates. If taken in large amounts, goldenseal can cause seizures and respiratory failure and may affect contraction of the heart.

Pregnancy and Lactation

Goldenseal and its active isoquinoline alkaloids, hydrastine and berberine, should be avoided in pregnancy because they can stimulate uterine contractions and induce labor. Although dosage information and clinical reports are lacking, goldenseal has been used traditionally as an abortifacient.

Berberine can displace bilirubin from serum albumin, causing concern about exposure of newborn infants, because bilirubin can build up in the infant's brain, causing brain damage. No data exist on the excretion of any components of goldenseal into breastmilk or on the safety and efficacy of goldenseal in nursing mothers. Women who are pregnant or breastfeeding should not use goldenseal, and it should not be given to infants. The berberine constituent of goldenseal can be harmful to newborns.

Potential Toxicology

Few studies have also suggested the possible neurotoxic, hepatotoxic, and phototoxic activities of goldenseal extract and its alkaloids. Animal studies have suggested potential liver toxicity with goldenseal root, but this occurred at very high doses over long-term ingestion. Laboratory studies demonstrating phototoxicity suggest this would be more likely from topical rather than supplement use.

Women who are pregnant or breastfeeding, neonates, and people who have seizure disorders or problems with blood clotting should not take goldenseal.

Product Adulteration

As a consequence of the high cost of genuine goldenseal, some commercial products contain little or no goldenseal plant material. Coptis chinensis has been sold in place of "Chinese goldenseal" and has been found as an adulterant of goldenseal. Other species that contain berberine, such as Coptis japonica, Berberis aquifolium, Berberis spp., Rumex spp., and Xanthorhiza simplicissima, have been used to adulterate goldenseal. Botanical identity and composition are confirmed by macroscopic and microscopic examinations of rhizome and root, as well as by thin-layer chromatography (TLC).

Evidence Quality and Research Gaps

Large randomized, double-blind clinical studies need to be conducted on goldenseal supplements and their main alkaloids to provide more evidence on the mechanisms responsible for pharmaceutical activity, clinical efficacy, and safety of these products.

9. Conservation Status

Goldenseal is listed as "vulnerable" on the International Union for Conservation of Nature (IUCN) Red List of Threatened Species and is included in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) due to concerns of over-harvesting for commerce and decline in the wild.

Overharvesting of goldenseal has caused serious reductions in populations reported in Illinois, Ohio, Indiana, and eastern Kentucky. In 1997, goldenseal was listed on Appendix II of the Convention for International Trade on Endangered Species (CITES), an international treaty monitoring trade in threatened and endangered species. Designed to protect the species, this listing imposed controls on goldenseal trade.

Goldenseal is listed as an endangered species in Georgia, North Carolina, Vermont, Connecticut, Massachusetts, and Minnesota. The U.S. Fish and Wildlife Service has stated that goldenseal is either endangered, threatened, imperiled, rare, or uncommon in all 27 U.S. states which have native populations.

Wild goldenseal has been overharvested and is available in limited amounts. The plant is grown commercially but is expensive to cultivate. The United Plant Savers organization has placed goldenseal on its "At Risk" list, the most urgent conservation category, and actively promotes cultivation as an alternative to wild harvesting.

References

• National Center for Complementary and Integrative Health (NCCIH) — Goldenseal: Usefulness and Safety
• NIH/NCBI Bookshelf — Exposure Data: Some Drugs and Herbal Products (Hydrastis canadensis)
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• Ettefagh KA et al. — Goldenseal (Hydrastis canadensis L.) extracts synergistically enhance the antibacterial activity of berberine via efflux pump inhibition. PMC/PubMed, 2011
• Gurley BJ et al. — In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Drug Metabolism and Disposition. 2005
• Nguyen JT et al. — Assessing Transporter-Mediated Natural Product-Drug Interactions via In vitro-In vivo Extrapolation: Clinical Evaluation with a Probe Cocktail. PMC, 2021
• Gurley BJ et al. — Clinical assessment of CYP2D6-mediated herb-drug interactions in humans. PMC, 2008
• Chatterjee P, Franklin MR — Human cytochrome P450 inhibition and metabolic-intermediate complex formation by goldenseal extract. Drug Metabolism and Disposition. 2003
• Hamsa TP et al. — Inhibition of H1N1 influenza A virus growth and induction of inflammatory mediators by berberine and extracts of goldenseal. PubMed, 2011
• MSD Manual Professional Edition — Goldenseal
• Memorial Sloan Kettering Cancer Center — Goldenseal (Integrative Medicine)
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• ClinicalTrials.gov — Assessing Goldenseal-Drug Interactions Using a Probe Drug Cocktail Approach (NCT03772262)
• United Plant Savers — Goldenseal (Hydrastis canadensis) At-Risk Species Profile
• IUCN — Unregulated Wild Collection and Habitat Loss Lead to Vulnerable Status for Medicinal Goldenseal
• Houston E et al. — Identification of Goldenseal Habitat and Indicators in Pennsylvania, USA. Ecology and Evolution. 2025
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• Briggs GG et al. — Goldenseal. Drugs in Pregnancy and Lactation, Tenth Edition
• Pharmacy Times — Goldenseal Drug Interactions