Goldenseal (Hydrastis canadensis), also called orangeroot or yellow puccoon, is a perennial herb in the buttercup family Ranunculaceae, native to North America. It 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. Goldenseal reproduces both clonally through the rhizome and sexually, with clonal division more frequent than asexual reproduction. It takes between 4 and 5 years for a plant to reach sexual maturity, i.e. the point at which it produces flowers. Plants in the first stage, when the seed erupts and cotyledons emerge, can remain in this state one or more years. The second vegetative stage occurs during years two and three (and sometimes longer) and is characterized by the development of a single leaf and absence of a well developed stem. Finally, the third stage is reproductive, at which point flowering and fruiting occurs. This last stage takes between 4 and 5 years to develop. A second species from Japan, previously listed as Hydrastis palmatum, is now usually classified in another genus, as Glaucidium palmatum.
Description Hydrastis canadensis is a herbaceous perennial growing from a horizontal, yellowish rhizome that is thick with knobby knots. The finely hairy, upright, unbranched, stems grow to 15–50 centimetres (6–19+1⁄2 inches) tall. Fertile plants have a single stem with two palmately lobed leaves. Flowering plants produce a single terminal flower with no petals and three sepals and 12 or more conspicuous white pistils; flowering occurs for a short time in spring. Fertilized flowers grow into red, raspberry-like fruits with one or two seeds.
Constituents and modern pharmacology Goldenseal contains the isoquinoline alkaloids hydrastine, berberine, berberastine, hydrastinine, tetrahydroberberastine, canadine and canalidine. A related compound, 8-oxotetrahydrothalifendine, was identified in one study. The United States Pharmacopoeia requires goldenseal sold as a supplement to have hydrastine concentrations of at least 2% and berberine concentrations of at least 2.5%. The requirements in Europe are that hydrastine concentrations be at least 2.5% and that berberine concentrations at least 3%. The hydrastine concentrations of goldenseal plants range between 1.5% and 5%, while the berberine concentrations are usually between 0.5% and 4.5%. Goldenseal is harvested for its rhizomes because the concentrations of hydrastine and berberine in the shoots do not meet these requirements. Berberine and hydrastine act as quaternary bases and are poorly soluble in water but freely soluble in alcohol. The herb seems to have synergistic antibacterial activity over berberine in vitro, possibly as a result of efflux pump inhibitory activity.
Distribution and habitat Found in southeastern Canada and the eastern United States, the plant grows in mesic forests under deciduous trees. It is found in sheltered ravines or on talus slopes. It seems to be intolerant of disturbances in the tree canopy and grazing. It can be found growing in association with other uncommon plants such as Jeffersonia diphylla (twinleaf) and Dicentra canadensis (squirrel corn).
Conservation Goldenseal became popular in the mid-19th century. By 1905, the herb was much less plentiful because of overharvesting and habitat destruction. Roots of goldenseal are listed in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), meaning a CITES permit to export is required. The U.S. Fish and Wildlife Service recommends that diggers and harvesters track sales and harvests and prove legality of all harvests. Canada, as well as 17 of the 27 U.S. states where goldenseal grows natively, have declared it as threatened, vulnerable or uncommon. More than 60 million goldenseal plants are picked each year without being replaced. Although goldenseal's geographical range is wide, it is found in small quantities in these habitats. The core of the herb's range is in the Ohio River Valley, but its population there has decreased by almost half. The process of mountain top removal mining has recently put the wild goldenseal population at major risk from loss of habitat. Many herbalists urge caution in choosing products containing goldenseal, as they may have been harvested in an unsustainable manner rather than having been organically cultivated. There are several berberine-containing plants that can serve as useful alternatives, including Chinese coptis, yellowroot or Oregon grape root.
Toxicity According to the American Cancer Society, "Goldenseal can have toxic side effects, and high doses can cause death." Side effects of goldenseal may include "digestive complaints, nervousness, depression, constipation, rapid heartbeat, diarrhea, stomach cramps and pain, mouth ulcers, nausea, seizures, vomiting, and central nervous system depression. High doses may cause breathing problems, paralysis, and even death. Long-term use may lead to vitamin B deficiency, hallucinations, and delirium." In addition, goldenseal may cause brain damage to newborn babies if given directly or if taken by breastfeeding or pregnant mothers, and may affect blood pressure unpredictably because it contains several compounds that have opposite effects on blood pressure. Taking goldenseal over a long period of time can reduce absorption of B vitamins, and it is cautioned to avoid goldenseal during pregnancy and lactation, with gastrointestinal inflammation and with pro-inflammatory disorders. A 2011 study found rats fed goldenseal constantly for two years had a greater tendency to develop tumors. Goldenseal has been found to have inhibited cytochrome P450 CYP2D6, CYP3A4 and CYP3A5 activity by approximately 40%, a statistically and clinically significant reduction. CYP2D6 is a known metabolizer of many commonly used pharmaceuticals, such as antidepressants (including all SSRIs except for fluvoxamine), neuroleptics, codeine, and Metformin. Combining goldenseal with such medications should be done with caution and under the supervision of a doctor as it can lead to serious, perhaps fatal, toxicity. Those with a genetic deficiency in these enzymes are at particular risk.
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