Hydrastis Canadensis
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''For the magazine from West Virginia see
Goldenseal (magazine) ''Goldenseal'' is a quarterly magazine devoted to West Virginia traditional life, published by the West Virginia Department of Arts, Culture and History in West Virginia. Mission ''Goldenseal'' documents the state's cultural background and r ...
'' Goldenseal (''Hydrastis canadensis''), also called orangeroot or yellow puccoon, is a
perennial A perennial plant or simply perennial is a plant that lives more than two years. The term ('' per-'' + '' -ennial'', "through the years") is often used to differentiate a plant from shorter-lived annuals and biennials. The term is also wide ...
herb In general use, herbs are a widely distributed and widespread group of plants, excluding vegetables and other plants consumed for macronutrients, with savory or aromatic properties that are used for flavoring and garnishing food, for medicinal ...
in the
buttercup ''Ranunculus'' is a large genus of about almost 1700 to more than 1800 species of flowering plants in the family Ranunculaceae. Members of the genus are known as buttercups, spearworts and water crowfoots. The genus is distributed in Europe, ...
family
Ranunculaceae Ranunculaceae (buttercup or crowfoot family; Latin "little frog", from "frog") is a family of over 2,000 known species of flowering plants in 43 genera, distributed worldwide. The largest genera are ''Ranunculus'' (600 species), ''Delphinium' ...
, native to North America. It may be distinguished by its thick, yellow knotted
rootstock A rootstock is part of a plant, often an underground part, from which new above-ground growth can be produced. It could also be described as a stem with a well developed root system, to which a bud from another plant is grafted. It can refer to a ...
. The stem is purplish and hairy above ground and yellow below ground where it connects to the yellow
rhizome In botany and dendrology, a rhizome (; , ) is a modified subterranean plant stem that sends out roots and shoots from its nodes. Rhizomes are also called creeping rootstalks or just rootstalks. Rhizomes develop from axillary buds and grow hori ...
. 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 Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...
, previously listed as ''Hydrastis palmatum'', is now usually classified in another
genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In the hierarchy of biological classification, genus com ...
, as '' Glaucidium palmatum''.


Description

''Hydrastis canadensis'' is a
herbaceous Herbaceous plants are vascular plants that have no persistent woody stems above ground. This broad category of plants includes many perennials, and nearly all annuals and biennials. Definitions of "herb" and "herbaceous" The fourth edition of t ...
perennial A perennial plant or simply perennial is a plant that lives more than two years. The term ('' per-'' + '' -ennial'', "through the years") is often used to differentiate a plant from shorter-lived annuals and biennials. The term is also wide ...
growing from a horizontal, yellowish
rhizome In botany and dendrology, a rhizome (; , ) is a modified subterranean plant stem that sends out roots and shoots from its nodes. Rhizomes are also called creeping rootstalks or just rootstalks. Rhizomes develop from axillary buds and grow hori ...
that is thick with knobby knots. The finely hairy, upright, unbranched, stems grow to tall. Fertile plants have a single stem with two palmately lobed
leaves A leaf (plural, : leaves) is any of the principal appendages of a vascular plant plant stem, stem, usually borne laterally aboveground and specialized for photosynthesis. Leaves are collectively called foliage, as in "autumn foliage", wh ...
. Flowering plants produce a single terminal flower with no petals and three
sepal A sepal () is a part of the flower of angiosperms (flowering plants). Usually green, sepals typically function as protection for the flower in bud, and often as support for the petals when in bloom., p. 106 The term ''sepalum'' was coined b ...
s and 12 or more conspicuous white
pistil Gynoecium (; ) is most commonly used as a collective term for the parts of a flower that produce ovules and ultimately develop into the fruit and seeds. The gynoecium is the innermost whorl of a flower; it consists of (one or more) ''pistils'' ...
s; 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 Hydrastine is an isoquinoline alkaloid which was discovered in 1851 by Alfred P. Durand. Hydrolysis of hydrastine yields hydrastinine, which was patented by Bayer as a haemostatic drug during the 1910s. It is present in ''Hydrastis canadensis'' ...
,
berberine Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as ''Berberis vulgaris'' (barberry), ''Berberis aristata'' (tree turmeric), ''Mahonia aquifolium'' (Oregon grape), ''Hydra ...
, berberastine,
hydrastinine Hydrastinine is a semisynthetic alkaloid from the hydrolysis of the alkaloid hydrastine, which was found naturally in small quantities in ''Hydrastis canadensis'' L. (Ranunculaceae). Hydrastinine was produced by oxidative splitting of hydrastine ...
, tetrahydroberberastine,
canadine (''S'')-Canadine, also known as (''S'')-tetrahydroberberine and xanthopuccine, is a benzylisoquinoline alkaloid (BIA), of the protoberberine structural subgroup, and is present in many plants from the family Papaveraceae, such as '' Corydalis yan ...
and canalidine. A related compound, 8-oxotetrahydrothalifendine, was identified in one study. The ''
United States Pharmacopoeia The ''United States Pharmacopeia'' (''USP'') is a pharmacopeia (compendium of drug information) for the United States published annually by the United States Pharmacopeial Convention (usually also called the USP), a nonprofit organization that ...
'' 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 ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
'', possibly as a result of
efflux pump In microbiology, efflux is the moving of a variety of different compounds out of cells, such as antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals, bacterial metabolites and neurotransmitters. All micr ...
inhibitory activity.


Distribution and habitat

Found in southeastern
Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...
and the eastern
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
, the plant grows in mesic forests under
deciduous In the fields of horticulture and Botany, the term ''deciduous'' () means "falling off at maturity" and "tending to fall off", in reference to trees and shrubs that seasonally shed leaves, usually in the autumn; to the shedding of petals, aft ...
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 ''Dicentra canadensis'', the squirrel corn, is a flowering plant from eastern North America with oddly shaped white flowers and finely divided leaves. Description Squirrel corn has small yellow clustered bulblets (looking roughly like kernels o ...
'' (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 CITES (shorter name for the Convention on International Trade in Endangered Species of Wild Fauna and Flora, also known as the Washington Convention) is a multilateral treaty to protect endangered plants and animals from the threats of interna ...
), meaning a CITES permit to export is required. The
U.S. Fish and Wildlife Service The United States Fish and Wildlife Service (USFWS or FWS) is an agency within the United States Department of the Interior dedicated to the management of fish, wildlife, and natural habitats. The mission of the agency is "working with othe ...
recommends that diggers and harvesters track sales and harvests and prove legality of all harvests.Robbins, C.S., 2000. Comparative analysis of management regimes and medicinal plant trade monitoring mechanisms for American ginseng and goldenseal. ''Conservation Biology'', ''14''(5), pp.1422–1434. 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 The Ohio River is a long river in the United States. It is located at the boundary of the Midwestern and Southern United States, flowing southwesterly from western Pennsylvania to its mouth on the Mississippi River at the southern tip of Illinoi ...
, but its population there has decreased by almost half. The process of
mountain top removal Mountaintop removal mining (MTR), also known as mountaintop mining (MTM), is a form of surface mining at the summit or summit ridge of a mountain. Coal seams are extracted from a mountain by removing the land, or overburden, above the seams. Thi ...
mining has recently put the wild goldenseal population at major risk from loss of habitat. Many
herbalist Herbal medicine (also herbalism) is the study of pharmacognosy and the use of medicinal plants, which are a basis of traditional medicine. With worldwide research into pharmacology, some herbal medicines have been translated into modern remed ...
s urge caution in choosing products containing goldenseal, as they may have been harvested in an
unsustainable Specific definitions of sustainability are difficult to agree on and have varied in the literature and over time. The concept of sustainability can be used to guide decisions at the global, national, and individual levels (e.g. sustainable livin ...
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 ''Mahonia aquifolium'', the Oregon grape or holly-leaved barberry, is a species of flowering plant in the family Berberidaceae, native to western North America. It is an evergreen shrub growing tall and wide, with pinnate leaves consisting of sp ...
root.


Toxicity

According to the
American Cancer Society The American Cancer Society (ACS) is a nationwide voluntary health organization dedicated to eliminating cancer. Established in 1913, the society is organized into six geographical regions of both medical and lay volunteers operating in more than ...
, "Goldenseal can have toxic side effects, and high doses can cause death."Goldenseal
American Cancer Society.
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,Goldenseal
WebMD.
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 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
CYP2D6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D ...
,
CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
and
CYP3A5 Cytochrome P450 3A5 is a protein that in humans is encoded by the ''CYP3A5'' gene. Tissue distribution ''CYP3A5'' encodes a member of the cytochrome P450 superfamily of enzymes. Like most of the cytochrome P450, the CYP3A5 is expressed in the ...
activity by approximately 40%, a statistically and clinically significant reduction. CYP2D6 is a known metabolizer of many commonly used pharmaceuticals, such as
antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
s (including all
SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...
s except for
fluvoxamine Fluvoxamine, sold under the brand name Luvox and Faverin among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is primarily used to treat major depressive disorder and obsessive–compulsive disorder ...
),
neuroleptic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...
s,
codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...
, and
Metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
. 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.


Cultivation

As of 1998, only 2.4% of goldenseal plant material originated from a cultivated source rather than wild harvest, although that number was projected to rise by 15–30% over the next several years. In response to conservation concerns, research has expanded regarding the propagation success of wild plant material for commercial yield. Because goldenseal grows in patches of interconnected ramets reproducing asexually through clonal propagation, transplanting rhizome propagules into cultivated settings is possible.Albrecht, M.A. and McCarthy, B.C., 2006. Comparative analysis of goldenseal (Hydrastis canadensis L.) population re-growth following human harvest: implications for conservation. ''The American midland naturalist'', ''156''(2), pp.229–236. Seed propagation is also feasible and has advantages such as lower cost and greater genetic variability, but is considered difficult and unpredictable.Burkhart, E.P. and Jacobson, M.G., 2009. Transitioning from wild collection to forest cultivation of indigenous medicinal forest plants in eastern North America is constrained by lack of profitability. ''Agroforestry systems'', ''76''(2), pp.437–453. Goldenseal may be commercially cultivated through agroforestry in natural settings mirroring the plant's ecological environment, or on farms with artificial shade canopies. Another propagation method of goldenseal utilizes a controlled environment such as a greenhouse growing lab where the plant's environmental needs such as light, water and temperature are artificially simulated. Crop selection and biotechnology experimentation may be employed to increase yield and pharmacological potency. Controlled environments can greatly reduce the amount of time required to grow goldenseal to its desired harvestable state. While forest-cultivated plants double in mass every three to five years, plants can double in mass every 15 weeks in growth chambers and triple in growth when in a course soil medium. Subculturing can take place every 30 days to mass-propagate the plant. Another option is cultivating goldenseal in new regions. An experiment conducted by Douglas et al. grew goldenseal over a six-year period in a warm, temperate environment in New Zealand. The yields were 74% higher in the sixth year of growth compared to the fourth year of growth, which is when goldenseal is normally harvested. The overall growth of the allochthonous goldenseal was comparable to that found in the United States, and the hydrastine and berberine concentrations were within the American and European standards. Cultivating goldenseal in a New Zealand environment that is similar to its home range is an option to maintain its population.


Research on harvest effects

Research completed by Albrecht and McCarthy shows that when goldenseal is harvested in the fall season, it has a faster population recovery than with midsummer harvests. However, a study by Douglas et al. showed that goldenseal has the highest concentrations of hydrastine and berberine in the early summer. Their research also showed that three to five years of growth will yield the highest concentration of alkaloids in the plant. Two experiments done by Sinclair and Catling on the effects of soil turnover, fertilization and transplanting of goldenseal show that disturbances actually benefit the growth of goldenseal. The results from the first growing season of the experiment showed that soil turnover and fertilization combined show the greatest increase in plant biomass, while the results after two growing seasons showed that this group also yielded the highest proportion of flowering plants, fruit production and seed production. Both experiments also showed that soil disturbances benefit the growth of goldenseal.


Uses

At the time of the
European colonization of the Americas During the Age of Discovery, a large scale European colonization of the Americas took place between about 1492 and 1800. Although the Norse had explored and colonized areas of the North Atlantic, colonizing Greenland and creating a short ter ...
, goldenseal was in extensive use among certain Native American tribes of North America, both as a medicine and as a coloring material. In 1798,
Benjamin Smith Barton Benjamin Smith Barton (February 10, 1766 – December 19, 1815) was an American botanist, naturalist, and physician. He was one of the first professors of natural history in the United States and built the largest collection of botanical specime ...
referred to the
Cherokee The Cherokee (; chr, ᎠᏂᏴᏫᏯᎢ, translit=Aniyvwiyaʔi or Anigiduwagi, or chr, ᏣᎳᎩ, links=no, translit=Tsalagi) are one of the indigenous peoples of the Southeastern Woodlands of the United States. Prior to the 18th century, t ...
use of goldenseal as a cancer treatment; he called attention to its properties as a bitter tonic, and as a local wash for
ophthalmia Ophthalmia (also called ophthalmitis) is inflammation of the eye. It results in congestion of the eyeball, often eye-watering, redness and swelling, itching and burning, and a general feeling of irritation under the eyelids. Ophthalmia can have d ...
. It became a favorite of the
Eclectics Eclecticism is a conceptual approach that does not hold rigidly to a single paradigm or set of assumptions, but instead draws upon multiple theories, styles, or ideas to gain complementary insights into a subject, or applies different theories in ...
from the time of Constantine Raffinesque in the 1830s. Tribes also used goldenseal for digestive issues, as an eyewash, as a diuretic and as a bitter. According to the American Cancer Society, "Available scientific evidence does not support claims that goldenseal is effective in treating cancer or other diseases." According to the
National Center for Complementary and Integrative Health The National Center for Complementary and Integrative Health (NCCIH) is a United States government agency which explores complementary and alternative medicine (CAM). It was initially created in 1991 as the Office of Alternative Medicine (OAM), ...
, "The scientific evidence does not support the use of goldenseal for any health-related purpose."Goldenseal
NCCIH.
In the early 20th century, it was used as a yellow dye, astringent, and insect repellent.


See also

*
Coptisine Coptisine is an alkaloid found in Chinese goldthread (''Coptis chinensis''), greater celandine, and opium. Famous for the bitter taste that it produces, it is used in Chinese herbal medicine along with the related compound berberine Berberine ...
*
List of ineffective cancer treatments This is a non-exhaustive list of alternative treatments that have been promoted to treat or prevent cancer in humans but which lack scientific and medical evidence of effectiveness. In many cases, there is scientific evidence that the alleged tr ...


References


Literature

* * John Uri Lloyd (1908). ''Hydrastis canadensis''. Lloyd Library, Cincinnati
PDF
* W. Scott Persons and Jeanine M. Davis (2005) ''Growing & Marketing Ginseng, Goldenseal & Other Woodland Medicinals'' Bright Mountain Books. * Richo Cech. (2002) ''Growing At-Risk Medicinal Herbs, Cultivation, Conservation and Ecology''


External links


Goldenseal: An Annotated Bibliography


* Bruce A. Ford
''Hydrastis''
in the ''Flora of North America'', Volume 3 {{Authority control Ranunculaceae Plants described in 1759 Plants used in traditional Native American medicine Flora of North America Plant dyes Taxa named by Carl Linnaeus