Goldenseal

Native American peoples of eastern North America used the rhizome for diarrhoea, dyspepsia, liver trouble, fevers, whooping cough, pneumonia and earache, to improve the appetite, and as a tonic ^{34Reference 34Ford · 1997Hydrastis canadensis — flora treatment (Ranunculaceae, family treatment by AView study →}.

It was applied as a wash for inflammation and sore eyes, which gave it the old name “eye balm”, and to chapped or cut lips ^{34Reference 34Ford · 1997Hydrastis canadensis — flora treatment (Ranunculaceae, family treatment by AView study →}. It was also used for skin conditions, wounds and ulcers, and as a yellow dye ^{18,35Reference 18Mandal et al. · 2020ReviewGoldenseal (Hydrastis canadensis L.) and its active constituents: a critical review of their efficacy and toxicological issues — reviewView study →Reference 35National Center for Complementary et al. · 2025Goldenseal — health information fact sheetView study →}.

The Eclectic physicians of nineteenth-century North America adopted goldenseal as a remedy for catarrh and for inflamed and ulcerated mucous membranes anywhere in the body.

Western herbal practice kept that use, giving the rhizome in short courses as a bitter and a mucous-membrane tonic that tones and dries over-secreting surfaces of the gut, sinuses and throat. In American folk medicine the root powder was also used for gastrointestinal disturbances, urinary complaints, bleeding, and infections of the skin, mouth and eyes ^{23Reference 23National Toxicology Program · 2010AnimalToxicology and carcinogenesis studies of goldenseal root powder (Hydrastis canadensis) in F344/N rats and B6C3F1 mice (feed studies) — animal carcinogenicity bioassayView study →}.

All of the antibacterial work is in vitro. The isolated alkaloids berberine, β-hydrastine, canadine and canadaline were tested with a goldenseal extract against Staphylococcus aureus, Streptococcus sanguis, E. coli and Pseudomonas aeruginosa, and the authors judged the results a rational basis for the traditional antibacterial use ^{6Reference 6Scazzocchio et al. · 2001In vitroAntibacterial activity of Hydrastis canadensis extract and its major isolated alkaloids — in vitroView study →}.

A goldenseal leaf extract inhibited MRSA at a lower concentration than berberine alone (MIC 75 vs 150 µg/mL). The leaf extract, but not the isolated alkaloids, also blocked quorum sensing in MRSA and reduced its toxin production ^{3Reference 3Cech et al. · 2012In vitroQuorum quenching and antimicrobial activity of goldenseal (Hydrastis canadensis) against methicillin-resistant Staphylococcus aureus (MRSA) — in vitroView study →}.

The synergy comes from the aerial parts. Extracts of the leaves and stems blocked the NorA efflux pump of S. aureus, while the root extract did not, although the roots hold more alkaloid ^{2Reference 2Ettefagh et al. · 2011In vitroGoldenseal (Hydrastis canadensis L.) extracts synergistically enhance the antibacterial activity of berberine via efflux pump inhibition — in vitroView study →}. Fractionation traced the effect to the C-methyl flavonoids sideroxylin, 8-desmethyl-sideroxylin and 6-desmethyl-sideroxylin, which have no antibacterial action of their own ^{1,4Reference 1Junio et al. · 2011In vitroSynergy-directed fractionation of botanical medicines: a case study with goldenseal (Hydrastis canadensis) — in vitroView study →Reference 4Britton et al. · 2018In vitroBiochemometrics to identify synergists and additives from botanical medicines: a case study with Hydrastis canadensis (goldenseal) — in vitroView study →}.

Against the oral bacterium Streptococcus mutans, berberine had an additive effect with a C-methyl flavonoid isolated from the root ^{7Reference 7Hwang et al. · 2003In vitroAntimicrobial constituents from goldenseal (rhizomes of Hydrastis canadensis) against selected oral pathogens — in vitroView study →}.

Gap: all data are laboratory MICs against cultured bacteria. There is no clinical trial, and use on the skin and mucous membranes, the traditional route, is untested in people.

Methanol extracts of goldenseal rhizome inhibited 15 strains of H. pylori in vitro, with an MIC50 of 12.5 µg/mL. Berberine (MIC50 12.5 µg/mL) and β-hydrastine (100 µg/mL) were identified as the active constituents ^{8Reference 8Mahady et al. · 2003In vitroIn vitro susceptibility of Helicobacter pylori to isoquinoline alkaloids from Sanguinaria canadensis and Hydrastis canadensis — in vitroView study →}.

A screen of 21 herbal extracts placed goldenseal among the most active against H. pylori ^{9Reference 9Cwikla et al. · 2010In vitroInvestigations into the antibacterial activities of phytotherapeutics against Helicobacter pylori and Campylobacter jejuni — in vitroView study →}.

Gap: in vitro activity does not establish that oral goldenseal reaches inhibitory concentrations in the stomach or clears the infection.

Berberine has documented anti-inflammatory actions, reviewed for inflammatory bowel disease in cell and animal work ^{12Reference 12Habtemariam · 2016ReviewBerberine and inflammatory bowel disease: a concise reviewView study →}.

Two commercial goldenseal preparations had little direct effect on resting mouse macrophages. When the macrophages were stimulated with bacterial lipopolysaccharide, goldenseal reduced their output of TNF-α, IL-6, IL-10 and IL-12 in a dose-dependent way ^{10Reference 10Clement-Kruzel et al. · 2008In vitroImmune modulation of macrophage pro-inflammatory response by goldenseal and Astragalus extracts — in vitroView study →}.

In influenza-infected macrophages, berberine strongly reduced TNF-α and PGE2 production, separately from its antiviral effect ^{11Reference 11Cecil et al. · 2011In vitroInhibition of H1N1 influenza A virus growth and induction of inflammatory mediators by the isoquinoline alkaloid berberine and extracts of goldenseal (Hydrastis canadensis) — in vitroView study →}.

Gap: the clearest data belong to isolated berberine, and the goldenseal work is limited to cultured cells.

Goldenseal and its alkaloids show antifungal activity in the laboratory, mostly through berberine. Berberine’s activity against Candida, including drug-resistant strains and biofilms, has been reviewed ^{15Reference 15Ding et al. · 2024ReviewInhibitory effects of berberine on fungal growth, biofilm formation, virulence, and drug resistance — reviewView study →}. In checkerboard assays, goldenseal extract combined synergistically with other plant extracts against Candida albicans, most strongly with Alpinia officinarum ^{13Reference 13Cho et al. · 2026In vitroSynergistic antifungal effects of botanical extracts against Candida albicans — in vitroView study →}.

The combined root alkaloids affected the germination of Fusarium fungi from the goldenseal root zone and stimulated one isolate to produce the mycotoxin zearalenone ^{14Reference 14Tims et al. · 2007In vitroEffects of root isoquinoline alkaloids from Hydrastis canadensis on Fusarium oxysporum isolated from Hydrastis root tissue — in vitroView study →}.

Gap: all of it is culture work, with nothing in an animal or a person.

Berberine strongly inhibited the growth of H1N1 influenza A in macrophage-like cells and human lung epithelial cells, but not in MDCK kidney cells. It appeared to block the trafficking and maturation of viral proteins ^{11Reference 11Cecil et al. · 2011In vitroInhibition of H1N1 influenza A virus growth and induction of inflammatory mediators by the isoquinoline alkaloid berberine and extracts of goldenseal (Hydrastis canadensis) — in vitroView study →}.

Ethanol extracts of goldenseal were also effective at high concentrations, but less so than purified berberine when diluted ^{11Reference 11Cecil et al. · 2011In vitroInhibition of H1N1 influenza A virus growth and induction of inflammatory mediators by the isoquinoline alkaloid berberine and extracts of goldenseal (Hydrastis canadensis) — in vitroView study →}.

Gap: one study, one virus and a few cell lines, with no animal or human data.

Goldenseal is often sold as an “immune stimulant”, frequently with Echinacea. In a six-week rat study, Echinacea raised both the primary and secondary IgG responses to a new antigen, while goldenseal raised only the primary IgM response during the first two weeks ^{16Reference 16Rehman et al. · 1999AnimalIncreased production of antigen-specific immunoglobulins G and M following in vivo treatment with Echinacea angustifolia and Hydrastis canadensis — animal (rat)View study →}.

On resting macrophages, goldenseal had little direct stimulating effect ^{10Reference 10Clement-Kruzel et al. · 2008In vitroImmune modulation of macrophage pro-inflammatory response by goldenseal and Astragalus extracts — in vitroView study →}.

Gap: there is no human evidence, and the animal effect was limited to early antibody production.

A total ethanolic goldenseal extract relaxed guinea-pig trachea precontracted with carbachol. Of its alkaloids, canadaline was the most potent, followed by canadine, berberine and β-hydrastine ^{17Reference 17Abdel-Haq et al. · 2000Relaxant effects of Hydrastis canadensis L. and its major alkaloids on guinea pig isolated trachea — ex vivo animalView study →}.

The authors suggested the alkaloids act through adrenergic and adenosine receptors, but judged the data insufficient for firm conclusions ^{17Reference 17Abdel-Haq et al. · 2000Relaxant effects of Hydrastis canadensis L. and its major alkaloids on guinea pig isolated trachea — ex vivo animalView study →}.

Gap: a single isolated-tissue study at concentrations that cannot be related to an oral dose.

CYP3A. In healthy adults, a single 3 g dose or 1 g three times daily for six days raised the blood levels of midazolam, a CYP3A test drug, by 40–60%. The effect was mainly on CYP3A in the gut wall, and β-hydrastine was the alkaloid chiefly responsible ^{5Reference 5Nguyen et al. · 2023In vitroAn integrative approach to elucidate mechanisms underlying the pharmacokinetic goldenseal–midazolam interaction — in vitro and PBPK modellingView study →}.

CYP2D6. In 16 healthy volunteers, 14 days of goldenseal inhibited CYP2D6 activity by about 50% ^{19Reference 19Gurley et al. · 2008RCTClinical assessment of CYP2D6-mediated herb–drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St John’s wort, and Echinacea — randomised human studyView study →}. In laboratory studies, goldenseal extracts also inhibited CYP2C9 and CYP2C8 ^{21,22Reference 21Chatterjee et al. · 2003In vitroHuman cytochrome P450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components — in vitroView study →Reference 22Etheridge et al. · 2007In vitroAn in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts — in vitroView study →}.

Not every drug is affected. Fourteen days of goldenseal root did not change the pharmacokinetics of indinavir in 10 healthy volunteers ^{20Reference 20Sandhu et al. · 2003Influence of goldenseal root on the pharmacokinetics of indinavir — human crossover studyView study →}. In 20 healthy volunteers, 14 days of goldenseal left digoxin, a P-glycoprotein test drug, essentially unchanged ^{42Reference 42Gurley et al. · 2007Clinical trialEffect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans — human studyView study →}.

Transporters. In 16 healthy volunteers, goldenseal raised midazolam exposure by 43% but did not change rosuvastatin or furosemide, drugs carried by the OATP1B, BCRP and OAT transporters ^{41Reference 41Nguyen et al. · 2021Clinical trialAssessing transporter-mediated natural product-drug interactions via in vitro-in vivo extrapolation: clinical evaluation with a probe cocktail — human studyView study →}.

Metformin. In healthy adults, goldenseal lowered metformin levels by about a quarter ^{35,41Reference 35National Center for Complementary et al. · 2025Goldenseal — health information fact sheetView study →Reference 41Nguyen et al. · 2021Clinical trialAssessing transporter-mediated natural product-drug interactions via in vitro-in vivo extrapolation: clinical evaluation with a probe cocktail — human studyView study →}. In adults with type 2 diabetes, there was no clinically meaningful change overall, but metformin exposure fell by about 20% at low metformin doses ^{30Reference 30Nguyen et al. · 2025Clinical trialThe pharmacokinetic interaction between metformin and the natural product goldenseal is metformin dose-dependent: a three-arm crossover study in adults with type 2 diabetes — clinical trialView study →}. In laboratory tests, goldenseal extract blocked the gut transporters that take up metformin, and in mice it lowered peak metformin levels by about 30% ^{31Reference 31Oyanna et al. · 2023AnimalGoldenseal-mediated inhibition of intestinal uptake transporters decreases metformin systemic exposure in mice — animal mechanistic studyView study →}.

Anyone taking prescription medicines should check with a prescriber before using goldenseal ^{35Reference 35National Center for Complementary et al. · 2025Goldenseal — health information fact sheetView study →}.

Liver tumours in rodents. In the US National Toxicology Program’s two-year feeding studies, goldenseal root powder caused liver tumours in male and female rats at the highest dose, about 1,175–1,340 mg/kg a day, and some evidence of liver tumours in male mice. Female mice were unaffected, and the powder was not mutagenic in bacterial tests ^{23,26Reference 23National Toxicology Program · 2010AnimalToxicology and carcinogenesis studies of goldenseal root powder (Hydrastis canadensis) in F344/N rats and B6C3F1 mice (feed studies) — animal carcinogenicity bioassayView study →Reference 26Dunnick et al. · 2013ReviewThe toxicity and pathology of selected dietary herbal medicines — review of animal carcinogenicity studiesView study →}.

The effect may be linked to berberine and its metabolite berberrubine, which inhibit topoisomerase ^{24Reference 24Dunnick et al. · 2011Investigating the potential for toxicity from long-term use of the herbal products goldenseal and milk thistle — animalView study →}. In human liver cells, berberine damaged DNA through topoisomerase II, and the damage caused by commercial goldenseal extracts rose with their berberine content ^{25Reference 25Chen et al. · 2013In vitroMechanism study of goldenseal-associated DNA damage — in vitroView study →}. The relevance to people taking goldenseal remains unknown ^{24Reference 24Dunnick et al. · 2011Investigating the potential for toxicity from long-term use of the herbal products goldenseal and milk thistle — animalView study →}.

Eyes and light. Berberine damaged human lens cells exposed to UVA in the laboratory. The authors advised caution with goldenseal eyewashes and lotions when the eyes are exposed to bright sunlight, and judged oral preparations unlikely to harm the eye ^{28Reference 28Chignell et al. · 2007In vitroPhotochemistry and photocytotoxicity of alkaloids from goldenseal (Hydrastis canadensis L.) 3: effect on human lens and retinal pigment epithelial cells — in vitroView study →}.

Product identity. Among 35 commercial products, several contained a different species or a mixture of plants ^{29Reference 29Wallace et al. · 2018Detection of adulteration in Hydrastis canadensis (goldenseal) dietary supplements via untargeted metabolomics — analyticalView study →}. In another survey, only 10 of 17 root products met proposed US Pharmacopeia standards for hydrastine and berberine ^{38Reference 38Edwards et al. · 2003Variations in alkaloid content of herbal products containing goldenseal — analyticalView study →}.