Hydrastis
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Goldenseal (''Hydrastis canadensis''), also called orangeroot or yellow puccoon, is a
perennial In horticulture, the term perennial ('' per-'' + '' -ennial'', "through the year") is used to differentiate a plant from shorter-lived annuals and biennials. It has thus been defined as a plant that lives more than 2 years. The term is also ...
herb Herbs are a widely distributed and widespread group of plants, excluding vegetables, with savory or aromatic properties that are used for flavoring and garnishing food, for medicinal purposes, or for fragrances. Culinary use typically distingu ...
in the
buttercup ''Ranunculus'' is a large genus of about 1750 species of flowering plants in the family Ranunculaceae. Members of the genus are known as buttercups, spearworts and water crowfoots. The genus is distributed worldwide, primarily in temperate an ...
family
Ranunculaceae Ranunculaceae (, buttercup or crowfoot family; Latin "little frog", from "frog") is a family (biology), family of over 2,000 known species of flowering plants in 43 genera, distributed worldwide. The largest genera are ''Ranunculus'' (600 spec ...
, 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 ...
. 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 Shoot (botany), shoots from its Node (botany), nodes. Rhizomes are also called creeping rootstalks or just rootstalks. Rhizomes develop from ...
. 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 is an island country in East Asia. Located in the Pacific Ocean off the northeast coast of the Asia, Asian mainland, it is bordered on the west by the Sea of Japan and extends from the Sea of Okhotsk in the north to the East China Sea ...
, previously listed as ''Hydrastis palmatum'', is now usually classified in another
genus Genus (; : genera ) is a taxonomic rank above species and below family (taxonomy), family as used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In bino ...
, 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 ...
perennial In horticulture, the term perennial ('' per-'' + '' -ennial'', "through the year") is used to differentiate a plant from shorter-lived annuals and biennials. It has thus been defined as a plant that lives more than 2 years. The term is also ...
growing from a horizontal, yellowish
rhizome In botany and dendrology, a rhizome ( ) is a modified subterranean plant stem that sends out roots and Shoot (botany), shoots from its Node (botany), nodes. Rhizomes are also called creeping rootstalks or just rootstalks. Rhizomes develop from ...
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 (: leaves) is a principal appendage of the stem of a vascular plant, usually borne laterally above ground and specialized for photosynthesis. Leaves are collectively called foliage, as in "autumn foliage", while the leaves, stem, ...
. 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 Etymology The term ''sepalum'' ...
s and 12 or more conspicuous white
pistil Gynoecium (; ; : gynoecia) 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 (botany), whorl of a flower; it consists ...
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. Nitric acid induced hydrolysis of hydrastine yields hydrastinine, which was patented by Bayer as a haemostatic drug in the early 1900's. It is present in ...
,
berberine Berberine is a Quaternary ammonium cation, quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids, occurring naturally as a secondary metabolite in some plants including species of ''Berberis'', from which its name ...
, berberastine, hydrastinine, 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 over 200-year old United States Pharmacopeial Convention (usually also called the USP), a nonprofi ...
'' 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'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
'', possibly as a result of
efflux pump An efflux pump is an active transporter in cells that moves out unwanted material. Efflux pumps are an important component in bacteria, particularly in their ability to remove antibiotics. The efflux process can also involve the movement of hea ...
inhibitory activity.


Distribution and habitat

Found in southeastern
Canada Canada is a country in North America. Its Provinces and territories of Canada, ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, making it the world's List of coun ...
and the eastern
United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
, 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 Leaf, 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 ''Jeffersonia'', also known as twinleaf or rheumatism root, is a small genus of herbaceous perennial plants in the family Berberidaceae. They are uncommon spring wildflowers and grow in limestone soils of rich deciduous forests. ''Jeffersonia'' ...
'' (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 of ...
'' (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 acronym 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 inte ...
), 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.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 river in the United States. It is located at the boundary of the Midwestern and Southern United States, flowing in a southwesterly direction from Pittsburgh, Pennsylvania, to its mouth on the Mississippi River in Cairo, ...
, 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 (topography), summit or summit ridge of a mountain. Coal seams are extracted from a mountain by removing the land, or overburden, ...
mining has recently put the wild goldenseal population at major risk from loss of habitat. Many
herbalist Herbal medicine (also called herbalism, phytomedicine or phytotherapy) is the study of pharmacognosy and the use of medicinal plants, which are a basis of traditional medicine. Scientific evidence for the effectiveness of many herbal treatments ...
s urge caution in choosing products containing goldenseal, as they may have been harvested in an
unsustainable Sustainability is a social goal for people to co-exist on Earth over a long period of time. Definitions of this term are disputed and have varied with literature, context, and time. Sustainability usually has three dimensions (or pillars): env ...
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 The American Cancer Society (ACS) is a nationwide non-profit organization dedicated to eliminating cancer. The ACS publishes the journals ''Cancer'', '' CA: A Cancer Journal for Clinicians'' and '' Cancer Cytopathology''. History The society w ...
, "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 Central nervous system depression (or CNS depression) is a nervous system disorder characterized by a severely impaired physiological state in which patients may exhibit decreased rate of breathing, decreased heart rate, and loss of consciousnes ...
. 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 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...
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. CYP2 ...
,
CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...
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 medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...
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 primarily work by ...
s except for
fluvoxamine Fluvoxamine, sold under the brand name Luvox among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is primarily used to treat major depressive disorder and, perhaps more-especially, obsessive–compu ...
),
neuroleptic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizoph ...
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 type2 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 colonization of the Americas, involving a number of European countries, took place primarily between the late 15th century and the early 19th century. The Norse explored and colonized areas of Europe a ...
, 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 (February10, 1766December19, 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 specimens in the ...
referred to the
Cherokee The Cherokee (; , or ) people are one of the Indigenous peoples of the Southeastern Woodlands of the United States. Prior to the 18th century, they were concentrated in their homelands, in towns along river valleys of what is now southwestern ...
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, and archaically obtalmy) 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 ey ...
. It became a favorite of the Eclectics 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 created in 1991 as the Office of Alternative Medicine (OAM), and r ...
, "The scientific evidence does not support the use of goldenseal for any health-related purpose." 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 Berberi ...
*
List of ineffective cancer treatments A list is a set of discrete items of information collected and set forth in some format for utility, entertainment, or other purposes. A list may be memorialized in any number of ways, including existing only in the mind of the list-maker, but ...


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 Northern America Plant dyes Taxa named by Carl Linnaeus