National Toxicology Program

3.0 PRODUCTION PROCESSES

Goldenseal products, when produced from the dried rhizome and root of the plant, contain at least 2.5% of the alkaloids, including berberine and hydrastine (Martin and Cook, 1961).

Berberine can be produced from cultures of Coptis japonica cells (Fujita and Tabata, 1987) and Thalictrum rugosum cells (Kim et al., 1990). Adding gibberellic acid to C. japonica cell cultures (Fujita, 1988), or cupric sulfate to T. rugosum (Kim et al., 1991) cell cultures, increases the yield. Also, producing C. japonica and T. rugosum at high cell density is essential for maximizing production yields (Kim et al., 1990; Piehl et al., 1988).

Hydrastine can be produced from berberine (Moniot and Shamma, 1976). The first step in the synthesis involves a ferricyanide oxidation of berberine to yield oxybisberberine. Treatment with methanolic hydrogen chloride yields 8-methoxyberberinephenolbetaine, which after hydration yields the hydrochloride salt of dehydronorhydrastine methyl ester. N-Alkylation then gives dehydrohydrastine methyl ester, and direct sodium borohydride reduction gives a 90% yield of a 1:2 mixture of (±)--hydrastine and (±)-beta-hydrastine.

4.0 PRODUCTION AND IMPORT VOLUMES

No data were found.

5.0 USES

Goldenseal was first used by Native Americans to treat wounds, ulcers, digestive disorders, and skin and eye ailments (Hamon, 1990). Over the years, goldenseal has been used to treat a variety of digestive and hemorrhagic disorders. It is thought to possess slight antiseptic, astringent, and hemostatic qualities when applied topically. It is claimed that goldenseal is effective in the treatment of hemorrhoids, disorders of the genito-urinary tract, upper respiratory inflammation and congestion, mucous membrane inflammation, eczema, pruritus, otorrhea, tinnitus and congestion/inflammation of the ear, and conjunctivitis, as well as for cancers, particularly of the ovary, uterus and stomach. Goldenseal has been used as a tonic, antiperiodic, diuretic (Hamon, 1990), and as a vaginal douche (Anonymous, 1994e). It is commonly consumed as an herbal tea (Hamon, 1990). For external use, it may be prepared by adding a teaspoon of root to 0.5 pint of water and used as a skin lotion. To prepare an eyewash, one teaspoon of ground goldenseal root and one teaspoon of boric acid are dissolved in one pint boiling water. The mixture is stirred, cooled, and the liquid is collected. For use as an eyewash, one teaspoon of the liquid is added to 0.5 cup of water (Anonymous, 1997b).

OTC preparations containing goldenseal are currently sold under the claim that they are effective in treating menstrual disorders, minor sciatica, and rheumatic and muscular pain (Hamon, 1990). OTC labels also assert goldenseal-containing products to be effective in treating allergy symptoms (Anonymous, 1997d), cold and flu symptoms (Anonymous, 1997e), motion sickness and nausea (Anonymous, 1996b), chronic diarrhea from protozoal, fungal, and bacterial infections (Anonymous, 1996a), and earaches and ear infections (Anonymous, 1994b). Goldenseal is included in dietary vitamin and mineral supplement tablets (Anonymous, 1997f) and is sometimes used to treat AIDS symptoms (Anonymous, 1996a). It is claimed to have the ability to cleanse the body of mucus, toxins, and waste (Anonymous, 1994c). Goldenseal is available in OTC preparations as an easy to swallow gel cap (Anonymous, 1996c); doses vary from 100 and 200 mg (Anonymous, 1994d) to 470 mg (Anonymous, 1994a).

Claims have been made that goldenseal is able to prevent the detection of illicit drugs in urine by inducing the rapid elimination of these compounds (Hamon, 1990). In one study (Mikkelsen and Ash, 1988), 15 g/L goldenseal tea produced false-negative results for tetrahydrocannibus (THC), but not for amphetamines, barbiturates, benzodiazepines, cocaine, or opiates. In another study (Schwarzhoff and Cody, 1993), adulteration of human urine with goldenseal root caused an apparent decrease in the concentrations of THC and barbiturate.

Berberine has been used as a bitter tonic (to improve stomach function), diaphoretic (sweat inducer), and antipyretic (Kulkarni et al., 1972), and for the treatment of skin diseases (including psoriasis) (Müller et al., 1995), liver diseases (Chi et al., 1994), eye infections, and diarrhea (Sabir et al., 1978), although it may not be effective for non-cholera diarrhea (Khin-Maung et al., 1985). In the treatment of psoriasis, the effectiveness of berberine appears to be related to its ability to inhibit hyperproliferation (Müller et al., 1995). Findings of one study did not support the usefulness of berberine in treating peptic ulcers and hyperacidity (Sabir et al., 1978).

Studies of berberine identified antiplatelet (Chu et al., 1994; cited by Peng et al., 1997), anticerebral ischemic (Wu and Liu, 1995; cited by Peng et al., 1997), vasodilatory (Chiou et al., 1991; cited by Peng et al., 1997), and antirrythmic (Wang and Tan, 1994; cited by Peng et al., 1997) pharmacologic properties. It is thought to increase ileal contractility and acetylcholine retention (Shin et al., 1993; cited by Peng et al., 1997) and is believed to be the active ingredient in Coptis rhizoma, which is used to treat amnesia (Lee, 1986; cited by Peng et al., 1997).

Berberine has also been used to treat a number of bacterial and parasitical infections, including cholera (Kulkarni et al., 1972), giardiasis (Choudry et al., 1972; Sabir et al., 1978), amoebiasis (Sabir et al., 1978), and dermal leishmaniasis (Sabir et al., 1978; Martin et al., 1978; Vennerstrom et al., 1990). There is conflicting evidence of the efficacy of berberine in the treatment of malaria (Vennerstrom and Klayman, 1988).

Results from a clinical trial also indicated that berberine is effective in improving cardiac performance in patients with heart failure (Marin-Neto et al., 1988). It appears to exert a direct depressive action on myocardial, vascular, and smooth musculature (Hahn et al., 1966; Herman and Chadwick, 1974; both cited by Creasey, 1977) and may have anticholesterolase activity (Sabir and Bhide, 1971).

In addition to its therapeutic uses, berberine is also used as a fluorescent stain in medical research (Kim et al., 1990). It is used to stain cells (Borodina et al., 1979), chromosomes (Ridler and Jennings, 1983), and energized mitochondria (Mikes and Dadák, 1983; Mikes and Yaguzhinskij, 1985).

Hydrastine is claimed to be an abortifacient, antibiotic, antiuterotic, antivaginitic, bactericide, central nervous system depressant, choleretic, convulsant, hemostat, hypertensive, hypotensive, pesticide, sedative, uterotonic, and vasoconstrictor (Beckstrom-Sternberg and Duke, 1997a).

6.0 ENVIRONMENTAL OCCURRENCE

Goldenseal is a small perennial plant indigenous to the hardwood forests of the eastern U.S. and Canada (Anonymous, 1997a). Currently, it is rarely found in the wild (Hamon, 1990).

Berberine is usually present in plants as a sulfate (HSDB, 1997). It is found in the rhizomes of Chinese Goldthread (Coptis chinensis FRANCH., 40,000-90,000 ppm), Generic Goldthread (Coptis spp., 40,000-90,000 ppm), and Huang-Lia (Coptis japonica, 40,000-70,000 ppm); in the roots of goldenseal (5000-60,000 ppm); in the bark of Huang Po (Phellodendron amurense RUPR., 8300-10,000 ppm); and in the plant parts of Barberry (Berberis vulgaris L., 10,000-30,000 ppm) and Prickly Poppy (Argemone mexicana L., 410 ppm) (Beckstrom-Sternberg and Duke, 1997b). Berberine is also a constituent (concentrations not given) of B. aristata, B. lamberti, B. asiatica, B. heterobotrus, B. crataegina, B. cretica, B. thunbergii, B. kawakamii, B. mingetsensis, B. morrisonensis, B. francesciferdinandi, B. koreana, B. iliensis, B. guimpeli, B. lycium, B. peteolaris, and B. amurensis var (Ikram, 1975).

Hydrastine is a constituent of goldenseal (15,000-40,000 ppm) (Beckstrom-Sternberg and Duke, 1997a) and B. laurina (concentration not given) (Ikram, 1975).

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