Goldenseal: Background. Actions

Historical Note

Goldenseal is indigenous to North America and was traditionally used by the Cherokees and then by early American pioneers. Preparations of the root and rhizome were used for gastritis, diarrhea, vaginitis, dropsy, menstrual abnormalities, eye and mouth inflammation, and general ulceration. In addition to this, the plant was used for dyeing fabric and weapons. Practitioners of the eclectic school created a high demand for goldenseal around 1847. This ensured the herb’s ongoing popularity in Western herbal medicine, but unfortunately led to it being named a threatened species in 1997. Today, most high-quality goldenseal is from cultivated sources.

Common Name


Other Names

Eye root, jaundice root, orange root, yellow root

Botanical Name / Family

Hydrastis canadensis (family Ranunculaceae)

Plant Parts Used

Root and rhizome

Chemical Components

Isoquinoline alkaloids, including hydrastine (1.5-5%), berberine (0.5-6%) and canadine (tetrahydroberberine, 0.5-1.0%). Other related alkaloids include canadaline, hydrastidine, corypalmineand isohydrastidine.

Clinical note — Isoquinoline alkaloids

Isoquinoline alkaloids are derived from phenylalanine or tyrosine and are most frequently found in the Ranunculaceae, Berberidaceaeand Papaveraceae families. This is a very large class of medicinally active compounds that include the morphinane alkaloids (morphine, thebaine and codeine), the ipecac alkaloids (emetine and cephaeline), the atropine alkaloid (boldine), and the protoberberines (berberine and hydrastine). Many other plants contain berberine, including Berberis vulgaris (barberry), Mahonia aquifolium/Berberis aquifolium (Oregon mountain grape), Berberis aristata (Indian barberry), Coptis chinensis (Chinese goldthread), Coptis japonica (Japanese goldthread) and Thalictrum minus.

Main Actions

A wealth of empirical data exists for the medicinal use of goldenseal; however, much of the research has been conducted using the chief constituent berberine. It is recommended that goldenseal products be standardised to contain at least 8 mg/mL of berberine and 8 mg/mL of hydrastine.


In vitro testing has demonstrated antibacterial activity of both the whole extract of goldenseal and the major isolated alkaloids (berberine, beta-hydrastine, canadine and canadaline) against Staphylococcus aureus, Streptococcus sanguis, Escherichia coli and Pseudomonas aeruginosa. In one recent study, two flavonoids isolated from goldenseal were shown to exhibit antibacterial activity against the oral pathogens Streptococcus mutans and Fusobacterium nucleatum. An added antimicrobial effect against S. mutans was noted with the addition of berberine.

The methanolic extract of the rhizome inhibited the growth of 15 strains of Helicobacter pylori in vitro. The authors identified berberine and beta-hydrastine as the main active constituents.

Berberine alone, and in combination with both ampicillin and oxacillin, has demonstrated strong antibacterial activity against all strains of MRSA in vitro; 90% inhibition was demonstrated with 64 µg/mL or less of berberine. Berberine was also found to enhance the effectivness of ampicillin and oxacillin against MRSA in vitro.

Many of the Berberis spp. contain the flavonolignan 5′-methoxyhydnocarpin, which inhibits the expression of the multidrug resistant efflux pumps; however, it is unknown whether goldenseal contains this compound.

Berberine inhibits the adherence of streptococci to host cells by aiding the release of an adhesin lipoteichoic acid (an acid that is responsible for the adhesion of the bacteria to the host tissue) from the streptococcal cell surface. Berberine is also able to dissolve lipoteichoic acid-fibronectin complexes once they have been formed. Berberine displays well-defined antimicrobial properties against certain bacteria and such data suggests that it may also be able to prevent adherence and destroy already formed complexes.

Berberine destroys cell wall and sterol biosynthesis in Candida spp. in vitro.


Berberine decreases intestinal activity by activating alpha-2-adrenoceptors and reducing cyclic adenosine monophosphate (cAMP). Berberine also inhibits intestinal ion secretion and inhibits toxin formation from microbes.

Berberine has demonstrated efficacy in vitro for many bacteria that cause infective diarrhea, including E. coli, Shigella dysenteriae, Salmonella paratyphi, Clostridium perfringensand Bacillus subtilus. It has also demonstrated activity in vitro against parasites that cause diarrhea, including Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis.

The effects of berberine on cholera toxin-induced water and electrolyte secretion were investigated in an experimental in vivo model. Secretions of water, sodium and chlorine were reduced 60-80 minutes after exposure to berberine.

Berberine did not alter ileal water or electrolyte transport in the control model. It produced a significant reduction in fluid accumulation caused by infection with E. coli in vivo. Oral doses of berberine before the toxin was introduced and intragastric injection after infection were both effective. Berberine was shown to inhibit by approximately 70% the secretory effects of Vibrio cholerae and E. coli in a rabbit ligated intestinal loop model. As in the other study, the drug was effective when given either before or after enterotoxin binding. In an investigation using pig jejunum, berberine demonstrated a reduction in water and electrolyte secretion after intraluminal perfusion with E. coli.

Berberine significantly slowed small intestine transit time in an experimental in vivo model. Berberine inhibited myoelectric activity, which appears to be partially mediated by opioid and alpha-adrenergic receptors. The antidiarrheal properties of berberine may be partially due to the constituents’ ability to delay small intestinal transit time.


Berberine may be effective for congestive heart failure and arrhythmia as it has demonstrated positive inotropic, negative chronotropic, antiarrhythmic and vasodilator properties.

After 8 weeks of treatment oral doses of berberine (10 mg/kg) improved cardiac function and prevented development of left ventricular hypertrophy induced by pressure overload in rats. Berberine was found to reduce left ventricular end-diastolic pressure, improve contraction and relaxation and decrease the amount of the atrophied heart muscle.

Berberine has also been found to increase cardiac output in dogs with left ventricular failure due to ischaemia. Over 10 days, intravenous administration of berberine (1 mg/kg, within 3 minutes) followed by a constant infusion (0.2 mg/kg/min, 30 minutes) increased the cardiac output and decreased left ventricular end-diastolic pressure, DBP and systemic vascular resistance, but did not affect heart rate. This study shows that berberine may be able to improve impaired left ventricular function by exerting positive inotropic effects and mild systemic vasodilatation. These results, although interesting, should be evaluated cautiously as the method of administration was intravenous. The hypotensive effects of the berberine derivative, 6-protoberberine (PTB-6) were studied in spontaneously hypertensive rats. PTB-6 lowered SBP in a dose-dependent manner (5 mg/kg:-31.1 ± 1.6 mmHg; 10 mg/kg:-42.4 ± 3.1 mmHg). The berberine derivative also reduced cardiac output and heart rate. The authors conclude that the antihypertensive effect of PTB-6 is probably caused by a central sympatholytic effect.


Berberine upregulates the LDL receptor (LDLR) by stabilising the LDLR mRNA. Hamsters fed a high-fat diet for 2 weeks, followed by treatment with oral doses of berberine (100 mg/kg) for 10 days demonstrated a 40% reduction of cholesterol, including a 42% reduction in LDL-cholesterol. No effect on HDL-cholesterol was noted.

Berberine may have potential as an anti-atherosclerotic agent because of a demonstrated inhibition of lysophosphatidylcholine (lysoPC)-induced DNA synthesis and cell proliferation in vascular smooth muscle cells (VSMCs) in vivo. Berberine also inhibited the migration of lysoPC-stimulated VSMCs and the activity of extracellular signal-regulated kinases, reduced transcription factor AP-1 and intra-cellular reactive oxygen species. This suggests that berberine may be useful for the prevention of atherosclerosis.


A glucose-lowering effect similar to metformin was observed in vitro for berberine; however, no effect was seen on insulin secretion.

Similarly, fasting blood glucose, total cholesterol and triglyceride levels significantly decreased after 8 weeks of treatment with 187.5 or 562.5 mg/kg of berberine in an experimental model of glucose intolerance. In an additional in vitro study using insulin secreted from pancreatic cells, incubated with berberine for 12 hours, the authors concluded that berberine increased insulin production. The relationship of these trials to oral doses in humans is unknown.

Blood glucose, blood lipids, muscle triglycerides and insulin sensitivity were measured before and after the ingestion of berberine or metformin in rats fed a high-fat diet. In this trial berberine and metformin improved insulin resistance and liver glycogen levels, but had no effect on blood glucose, insulin, lipid and muscle triglyceride levels. The study was able to demonstrate that berberine was as effective as metformin for improving insulin sensitivity in the rats.

Berberine inhibits alpha-glucosidase and therefore reduces the transport of glucose through the intestinal epithelium.


Berberine inhibits COX-2 transcriptional activity and reduces PG synthesis in vitro and in vivo. Berberine has been found to reduce proliferation of human lymphocytes in vitro by inhibiting DNA synthesis in activated cells.


Intragastric administration of the crude extract of goldenseal for 6 weeks increased the production of IgM in vivo. Berberine has also been found to induce IL-12 p40, a large subunit of IL-12, through the activation of p38 mitogen-activated protein kinase in mouse macrophages. lnterleukin-12 is crucial for the development of theThl immune response and thus may also have a therapeutic effect in reducing Th2 allergic disorders. A follow-up study demonstrated that pretreatment with berberine induced IL-12 production in stimulated macrophages and dendritic cells. Macrophages pretreated with berberine had an increased ability to induce IFN-gamma and a reduced ability to induce IL-4 in antigen-primed CD4+ T-cells. Increased levels of IL-12 appear to deviate CD4+ T-cells from theTh2 to theThl pathway. This inhibition of type 2 cytokine responses indicate that berberine may be an effective anti-allergic compound.

The immunosuppressive effects of berberine were investigated in an induced autoimmune model in vivo. Berberine was administered daily (10 mg/kg) for 3 days before intravenous induction of tubulo-interstitial nephritis (TIN).

Significantly less damage and an increase in renal function was demonstrated in the animals pretreated with berberine as compared to controls after 2 months. Berberine decreased CD3, CD4 and CD8 lymphocytes in comparison with non-treated animals. These results suggest that berberine may exert an immunosuppressive effect in a TIN model. Clinical trials in human kidney autoimmune diseases are warranted.


Berberine has demonstrated cytotoxic activity in vitro against many strains of human cancer cells. This is due in part to the reduction of COX-2 enzymes, damage to the cytoplasmic membrane and DNA fragmentation.

Theantitumour effects of berberine were investigated on malignant brain tumours in an in vitro and in vivo model. Berberine (150 mg/mL) demonstrated an ability to kill 91 % of cells in six human malignant brain tumour cell lines and 10 mg/kg exhibited an 80.9% cell kill rate against solid brain tumours in vivo. The addition of berberine to 1,3-bis(2-chloroethyl)-1 -nitrosourea increased cytotoxicity.

Other Actions

Anticatarrhal, astringent, bitter, choleretic, depurative, mucus membrane tonic, vulnerary and oxytocic.