Goldenseal

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Hydrastis canadensis L.

[Fam. Ranunculaceae]

Overview

Goldenseal is ranked among the top herbal supplements sold in natural food stores in the U.S. (Blumenthal et al., 1998) and it is often combined with echinacea (Echinacea spp.). In 2000, sales of goldenseal products ranked 12th in the natural food trade (NBJ, 2001). In 1998, sales of products that contain both goldenseal and echinacea, ranked fifth in mainstream stores, at $69.7 million (Blumenthal, 2001). Despite goldenseal’s popularity, clinical studies have been conducted on only one of its principal alkaloids, berberine. Berberine, hydrastine, and related isoquinoline alkaloids are the primary constituents thought responsible for goldenseal’s medicinal activity. Goldenseal is not used widely in Europe, and this may be the reason for the lack of clinical research (Tyler, 1998). Ethnomedical use dates to the Cherokee Indians, who used goldenseal root to treat skin diseases and sore or inflamed eyes. The Iroquois used the root for diarrhea, digestion, whooping cough, and pulmonary problems (Foster, 1996; Moerman, 1998). In the latter part of the 19th century, Eclectic physicians used goldenseal preparations primarily for acute or subacute inflammation of the mucous membranes (Felter and Lloyd, 1898), chronic inflammation of the stomach, and atonic dyspepsia associated with alcoholism (Blumenthal, 2001). Goldenseal root was official in the United States Pharmacopeia starting from 1860 (Lloyd, 1929), and up to five different preparations were listed in the USP until the 10th revision in 1926 (Boyle, 1991).

Due to its relatively high price, some “goldenseal” products sold in the U.S. may contain “goldenseal herb”, made with the leaves of the plant containing approximately 10% of the alkaloid levels usually found in the root. Some products have been known to be adulterated with the low cost goldthread root (Coptis chinensis) from China, a plant containing significant levels of berberine. Wild goldenseal was named a “threatened” species by CITES (Convention in Trade in Endangered Species) in 1997, thereby limiting its trade in international commerce (Bannerman, 1997). About 15–30% of domestic supplies of goldenseal are derived from cultivated sources within the U.S. (McGuffin, 1999).

Description

Goldenseal consists of the root and rhizome of Hydrastis canadensis L. [Fam. Ranunculaceae]. Its name derives from the seal-like scars on the rhizomes that are yellow or golden in color (Lloyd and Lloyd, 1884–85). The United States Pharmacopeia stipulates that the root and rhizome material must contain no less than 2.0% hydrastine and no less than 2.5% berberine (USPF, 2000).

Primary Uses

[Editors’ Note: Since there are no published clinical trials documenting scientifically the safe and effective use of goldenseal preparations in humans, despite significant empirical data, the editors have refrained from suggesting any primary uses.]

Berberine (Pharmaceutical Preparations)

Internal

Gastrointestinal

Diarrhea (Gupte, 1975; Khin et al., 1985; Rabbani et al., 1987)

External

Ophthalmic

Ocular trachoma infections (Babbar et al., 1982; Kholsa et al., 1992 Mohan et al., 1982)

Other Potential Uses

Goldenseal

Internal

Gastrointestinal

Dyspepsia (Bradley, 1992; Upton, 2001)

Gastritis (Bradley, 1992)

Gynecology

Menorrhagia (Bradley, 1992)

External

Eyewashes (Bradley, 1992)

Dosage

Internal

Dried rhizome and root: 0.5–1.0 g, 3 times daily (Bradley, 1992).

Tincture: (1:10, 60% ethanol), 2–4 ml (Bradley, 1992).

Fluid extract: (1:1, 60% ethanol), 0.3–1 ml (Bradley, 1992).

External

Eyewash: (0.2% sterile aqueous [non-alcoholic] berberine solution) 2 drops are placed in each eye, 3 times daily (Kholsa et al., 1992).

Duration of Administration

It may take up to a few days to a week for the herb to produce benefits. No known limitations on use (Tierra, 1998).

Chemistry

The active ingredients of goldenseal are isoquinoline alkaloids, mainly hydrastine and berberine (Bruneton, 1999). Other constituents include canadaline, canadine, hydrastidine, isohydrastidine, (S)-corypalmine, (S)-isocorypalmine, berberastine, 1-a-hydrastine, and chlorogenic acid (Bradley, 1992; Upton, 2001).

Pharmacological Actions

The following actions are primarily related to berberine, a constituent of goldenseal, and therefore, depending on berberine content, the pharmacological actions of goldenseal products may vary from those actions listed below.

Humans (berberine)

Anti-diarrheal: In cholera patients, berberine reduced cyclic adenosine by 77% (Khin et al., 1985). In diarrhea due to Vibrio cholerae and Escherichia coli, berberine reduced stool volume 30–50% without side effects (Rabbani, 1996).

Antiparasitic: In children with giardiasis, berberine demonstrated effectiveness compared with metronidazole without side effects (Gupte et al., 1975).

Cardiovascular: Decrease in systemic and pulmonary vascular resistance and left ventricular end-diastolic pressure; increase in stroke index, cardiac index, and left ventricular ejection fraction (Marin-Neto et al., 1988); suppression of ventricular premature contractions without severe side effects (Huang, 1990b).

Animal (berberine)

Stimulates immune function (Rehman et al., 1999); antiparasitic in hamsters with L. donovani amastigotes (Ghosh et al., 1985); anti-chlamydial effects in ocular trachoma (Babbar et al., 1982); positively inotropic and mild vasodilating effects in anesthesized dogs with ischemic left ventricular failure (Huang et al., 1992); anti-inflammatory, inhibits vascular permeability and swelling induced by drugs (Zhang and Shen, 1989).

In vitro (goldenseal)

The total extract of goldenseal demonstrated bactericidal activity against six strains of microorganism, including Staphylococcus aureus, Streptococcus sanguis, Escherichia coli, Pseudomonas aeruginosa, with a killing time of 4–30 minutes against all of the examined strains (Scazzochio et al., 2001).

In vitro (berberine)

Berberine is antimicrobial (Scazzocchio et al., 1998); inhibits smooth muscle contraction (Baldazzi et al., 1998); anti-inflammatory, inhibits platelet aggregation, platelet adhesion induced by ADP, and arachidonic acid; inhibits thrombus formation, inhibits collagen-induced thromboxane A2 release from platelets, and lowers plasma level of PGI2 in rabbits (Ckless et al., 1995; Wu and Liu, 1995; Huang et al., 1991; Muller and Ziereis, 1994; Misik et al., 1995).

Antiparasitic, amoebicidal at 0.5–1.0 mg/ml; preliminary results indicate cysticidal activity (Subbaiah and Amin, 1967); cardiovascular antiarrhythmic and proarrhythmic action in the cardiac muscle of dogs (Riccioppo, 1993); increases coronary artery flow (Huang, 1990a); bacteriostatic at low doses and a bacteriocide at higher doses (Bruneton, 1999).

Mechanism of Action

The following mechanisms primarily describe the action of berberine:

Increases antigen-specific immunoglobulin (IgM) production in vivo, demonstrated in goldenseal (Rehman et al., 1999).

Blocks a1 and a2. These receptors mediate smooth muscle contraction (Baldazzi et al., 1998).

Anti-diarrheal activity may result from the inhibition of intestinal ion secretion, inhibition of toxin formation, and inhibition of smooth muscle contraction in addition to antimicrobial effects (Birdsall and Kelly, 1997).

Inhibits ventricular tachyarrhythmias through potassium channel blocking effects (Hua and Wang, 1994).

Anti-trachomal through stimulating protective mechanism in the host (Babbar et al., 1982).

Stimulates bile secretion and bilirubin discharge (Birdsall and Kelly, 1997).

Contraindications

Goldenseal should not be used in cases of kidney disease, including kidney failure due to inadequate urinary excretion of its alkaloids. It should probably be avoided in acute inflammation of the stomach, based on a case report in which a bitters formula enhanced gastric acid secretions. It is contraindicated in cases of jaundice in newborns. One study in rats found berberine displaced bilirubin from serum albumin which may lead to kernicterus (nuclear jaundice) (Brinker, 2001).

Pregnancy and Lactation: Not for use during pregnancy (Brinker, 2001; McGuffin et al., 1997). Berberine can increase bilirubin in neonates, possibly leading to neonatal jaundice (Hobbs, 2000; Upton, 2001). It may also demonstrate uterine-stimulant activity, since this has been demonstrated in its constituents berberine, canadine, hydrastine, and hydrastinine (Farnsworth, 1975). There are no known contraindications during lactation, but goldenseal’s use should be avoided during lactation until further research has been conducted.

Adverse Effects

At recommended doses, goldenseal is considered nontoxic; berberine has also been well-tolerated in therapeutic doses (De Smet et al., 1992; Newall et al., 1996).

Drug Interactions

Goldenseal can potentially antagonize the anticoagulant activity of heparin. Studies in mice and rats have indicated hemodynamic properties of berberine, including an increase in the number of thrombocytes, decrease in the activity of factor XIII, and the promotion of blood coagulation (Ziablitskii et al., 1996).

American Herbal Products Association (AHPA) Safety Rating

Class 2b: Not to be used during pregnancy (McGuffin et al., 1997).

Regulatory Status

The following apply to goldenseal preparations, not berberine:

Canada: Acceptable as a drug but unacceptable as a non-medicinal ingredient in oral use products (Health Canada, 1995a; HPB, 1993). Not permitted as single-ingredient Traditional Herbal Medicine (THM) and may not be used at over 300 mg/day as component of multi-ingredient THMs (Health Canada, 1995b). Acceptable indications: Bitter digestive in multiple ingredient products (up to 75 mg/day), and as mild antiseptic in topical THM multiple-ingredient products (up to 15%) (HPB, 1993). As a single active ingredient, not acceptable for internal use except in homeopathic dilution (HPB, 1993; Health Canada 2001)

France: Official in French Pharmacopoeia (Bradley, 1992; Newall et al., 1996; Reynolds et al., 1989).

Germany: Dried underground parts official in German Homöopathisches Arzneibuch (HAB 1) containing no less than 3.0% alkaloids, calculated as berberine (GHP, 1993). Homeopathic indications: D1–D4 for chronic nasal catarrh; uterine hemorrhages, leucorrhea, and tonic (Roth et al., 1984).

Sweden: Natural product for external use (De Smet et al., 1993). No products containing goldenseal are presently registered in the Medical Products Agency’s (MPA) “Authorized Natural Remedies,” “Homeopathic Remedies,” or “Drugs” listings (MPA, 2001a, 2001b).

Switzerland: In homeopathic dilutions, approved as a component of multi-ingredient homeopathic drugs classified by the Interkantonale Kontrollstelle für Heilmittel (IKS) as List D medicinal products with sales limited to pharmacies and drugstores, without prescription (Morant and Ruppanner, 2001; Ruppanner and Schaefer, 2000).

U.K.: General Sale List, Schedule 1 (requires full Product License), Table A (internal or external use) (Bradley, 1992; Newall et al., 1996).

U.S.: Dietary supplement (USC, 1994). Subject of botanical monograph in development for the U.S. National Formulary
containing no less than 2.0% hydrastine and no less than 2.5% berberine (USP, 2002). The 1X mother tincture of rhizome and roots, 65% alcohol v/v, is a Class C over-the-counter drug official in the Homeopathic Pharmacopoeia of the United States (HPUS, 1996).

Clinical Review

Although modern, controlled clinical trials on goldenseal are lacking, some studies have been published on the alkaloid berberine. It is not generally possible or prudent to attempt to explain the activity of an herb based on the research on one of its primary active constituents. However, in the case of goldenseal, where no modern human trials are available in the literature, the research on the isolated alkaloid is indicative of the proposed activity of goldenseal and is consistent with the herb’s empirically-determined uses. Five studies are outlined in the following table, “Clinical Studies on Berberine,” including a total of 465 participants. All of these studies demonstrated positive effects for indications including diarrhea, ocular infections, and cardiovascular conditions. However, there may be questions regarding the safety of intravenous administration of berberine for cardiac conditions (e.g., ventricular arrhythmias) due to occurrence of torsades de pointes in 4 of 12 patients receiving 0.2mg/kg berberine i.v. (Marin-Neto et al., 1988). A comprehensive review of the cardiovascular effects of berberine suggest possible clinical usefulness in the treatment of arrhythmias and/or heart failure (Lau et al., 2001). There is no evidence that this issue is related to the oral use of lower goldenseal. Human studies on berberine have shown that it is absorbed poorly from the small intestines. Therefore, its antimicrobial action is only effective locally, i.e., in the gut. Berberine is excreted in the urine, so it may have some antimicrobial effect in the kidneys or urinary tract (Bergner, 1996). Berberine has also been tested clinically and shown to be efficacious at stimulating bile and bilirubin secretion, improving symptoms of chronic cholecystitis, and normalizing elevated tyramine levels in persons with cirrhosis of the liver (Watanabe et al., 1982). Berberine is reportedly effective as an adjunct to cancer therapy (Liu et al., 1991). Clinical studies on berberine have confirmed that it is effective for acute diarrhea (Sack and Froehlich, 1982; Kamat, 1967). Externally, it has been shown useful as an eyewash in treating trachoma, an infectious eye disease (Mohan et al., 1982).

Branded Products

Studies on berberine were conducted with generic, not specific, products.

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