Goldenseal
Goldenseal (Orange-root, Orangeroot; Hydrastis canadensis) is a perennial herb in the buttercup family Ranunculaceae, native to southeastern Canada and the northeastern United States. 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.  The plant bears 2 palmate, hairy leaves with 5-7 double-toothed lobes and single, small, inconspicuous flowers with greenish white stamens in the late spring.  It bears a single berry like a large raspberry with 10-30 seeds in the summer.
Herbal properties (whole herb): bitter, hepatic, alterative, anticatarrhal, anti-inflammatory, antimicrobial, laxative, emmenagogue, and oxytocic.
Goldenseal is often used as a multi-purpose remedy, having many different medicinal properties. In addition to working as a topical antimicrobial, it can also be taken internally as a digestion aid, and can remove canker sores when gargled with. Goldenseal may be purchased in salve,  tablet,  tincture form, or as a bulk powder. Goldenseal is often used to boost the medicinal effects of other herbs it is blended or formulated with.
A second species from Japan, previously listed as Hydrastis palmatum, is sufficiently distinct that it is now usually treated in a separate genus, as Glaucidium palmatum.

# Traditional usage
At the time of the European conquest of the Americas, goldenseal was in extensive use among certain Native American tribes of North America, as both as a medicine and as a coloring material. Prof. Benjamin Smith Barton in his first edition of "Collections for an Essay Toward a Materia Medica of the United States" (1798), refers to the Cherokee use of goldenseal as a cure for cancer. Later, he calls attention to its properties as a bitter tonic, and as a local wash for ophthalmia. It became a favorite of the Eclectics from the time of Constantine Raffinesque in the 1830s. It was introduced into Homoeopathic medicine by Prof. E. M. Hale, M. D., who was familiar with the Eclectic uses of the plant.
Goldenseal was extensively used for cancers and swellings of the breasts by the Eclectics, although it was not considered sufficient for cancer alone.  Hale recommended its use in hard swellings of the breast, while conium was used for smaller painless lumps. The two herbs alone or with phytolacca americana were used for cancers, along with alteratives like red clover.
Ellingwood's American Materia Medica lists goldenseal as being useful for functional disorders of the stomach, catarrhal gastritis, atonic dyspepsia, chronic constipation, hepatic congestion, cirrhosis, protracted fevers, cerebral engorgements of a chronic character, uterine subinvolution, in menorrhagia or metrorrhagia from the displaced uterus, post partum hemorrhage, catarrhal, ulcerating, aphthous, indolent and otherwise unhealthy conditions of mucous surfaces, leucorrhea, gallstones and breast swellings associated with the menses. 
Ellingwood cites one unusual use:
Cuthberton gave hydrastis canadensis as a tonic to a pregnant woman who had a goitre of recent appearance. The goitre was promptly cured. As a result of this observation, he treated twenty-five other cases of goitre at the time of puberty, or during the pregnant state. At times when interference with the function of the reproductive organs seemed to produce reflex irritation. He claims that every case was cured by this remedy. He gave the agent from six weeks to three months, three times a day after eating. One of the patients had become steadily worse under the use of iodine, the iodides, and thyroid extract. This patient began to improve as soon as hydrastis was given, and was promptly cured with this remedy alone
Herbalists today consider goldenseal an alterative, anti-catarrhal, anti-inflammatory, antiseptic, astringent, bitter tonic, laxative, and muscular stimulant.  They recommend goldenseal for gastritis, colitis, duodenal ulcers, loss of appetite and liver disease.  They discuss the astringent effect it has on mucous membranes of the upper respiratory tract, the gastrointestinal tract, the bladder, and rectum (applied topically), and the skin. Goldenseal is very bitter, which stimulates the appetite and aids digestion, and often stimulates bile secretion.    

# How goldenseal works
While most people assume that goldenseal has direct antimicrobial effects, it may work by more diffuse means.  Herbalist Paul Bergner, AHG, investigated the research and has been unable to find case reports where the level of intestinal pathogens are lower after taking goldenseal, although he has found many reports where symptoms were reduced.  In fact a study by Rabbani where men with e-coli induced diarrhea had 42-48% reduced symptoms after taking berberine showed unchanged levels of intestinal bacteria, pathogenic or otherwise. His conclusion on how it works:
One traditional use of goldenseal is as a mucous membrane tonic. Note that it does not have to come in contact with the mucous membranes to have this effect. Hold some goldenseal in your mouth for a minute or two, and you can feel the effect on the mucous membranes in your nose and sinuses. Traditional doctors stated that goldenseal increases the secretion of the mucous membranes. At the same time, goldenseal contains astringent factors, which also counter that flow. Thus it was referred to as a mucous membrane "alterative," increasing deficient flow but decreasing excessive flow. How this happens has not been determined by science, but is thoroughly supported by the traditional uses.... It is my opinion that goldenseal acts as an "antibiotic" to the mucous membranes not by killing germs directly, but by increasing the flow of healthy mucous, which contains its own innate antibiotic factors  IgA antibodies. This effect is unnecessary in the early stages of a cold or flu, when mucous is already flowing freely.
In addition to directly killing pathogens, as Mills and Bone cited below, and stimulating IgA antibodies, it appears likely that goldenseal shares with Mahonia (Oregon grape) and Berberis (Barberry) the ability to inhibit the drug resistance efflux pumps (MDR  pumps) of bacteria, as discussed below.

# Constituents and modern pharmacology
Goldenseal contains a isoquinoline alkaloids: hydrastine, berberine, berberastine, hydrastinine tetrahydroberberastine,  canadine, and canalidine. A related compound, 8-oxotetrahydrothalifendine was identified in one study. Berberine and Hydrastine act as quaternary bases and are poorly soluble in water but freely soluble in alcohol.
Multiple bacteria and fungi, along with selected protozoa and chlamydia are susceptible to
berberine in vitro. Berberine alone has weak antibiotic activity in vitro
since many microorganisms actively export it from the cell (although a whole herb is likely to work on the immune system as well as on attacking the microbes and hence have a stronger clinical effect than the antibiotic activity alone would suggest). Interestingly, there is some evidence for other
berberine-containing species synthesizing an efflux pump inhibitor that tends to prevent antibiotic resistance, a case of solid scientific evidence that the herb is superior to the isolated active principle. However, it is not yet known whether goldenseal contains a drug resistance efflux pump inhibitor, although many antimicrobial herbs do.

# Toxicity
Most of the research that is popularly attributed to goldenseal has actually been into the constituent berberine, which goldenseal has in common with a variety of other medicines including Oregon grape, coptis, phellodendron, barberry and yellow root. Constituents frequently act differently in isolation than a whole herb acts in the body.  In 1996, the committee of the European Union that regulates drugs placed Barberry (Berberis vulgaris) in a table of Herbal Drugs with Serious Risks without any Accepted Benefit because it contains berberine. This recommendation is so at odds with the long traditional use of barberry and other berberine-containing herbs that it appears incorrect. Paul Bergner investigated the literature and was able to find only a single report of potential adverse effects of berberis species, berberine-containing plants, or berberine itself in a computer search of the MEDLINE and TOXLINE databases of the U.S. National Library of Medicine. This was a study in China that showed that berberine sulfate is inappropriate for the treatment of newborn infants with prenatal jaundice . However that is not a likely scenario in a country where babies born jaundiced are hospitalized, but it does lend credence to the traditional advice not to take goldenseal or other berberine herbs during pregnancy.
Research into the toxicology and pharmacology of goldenseal has focused on berberine and hydrastine, which are antimicrobial, chloretic and each have a variety of other properties helping immunity.  But toxicity in a concentrated constituent does not translate to toxicity of the whole herb with its buffering compounds. In one study, the lethal dose (LD50) for rats was 12 times lower with hydrastine than with goldenseal extract.
Pregnant rats fed about 47 times the usual human dose of 26 mg/kg, had increased maternal liver weights, but there were no adverse fetal effects.  When goldenseal powder was fed at 300 times the standard human dose equivalence to rats, there were no developmental defects noted. 
The lethal dose (LD50) of berberine isolates in humans is thought to be 27.5 mg/kg. Berberine is absorbed slowly orally; it achieves peak concentrations in 4 hours and takes 8 hours to clear  
Berberine is excreted in the urine and human studies of berberine show evidence it can be absorbed through the skin.  Pharmacokinetic data is not available for hydrastine or goldenseal root
powder. Berberine in humans can cause blocking of receptors in smooth muscle,  blocking potassium channels in the heart and reducing ventricular tachycardia, inhibiting intestinal ion secretion and toxin formation in the gut and increasing bile secretion.
While goldenseal, like all alkaloid-rich herbs including coffee and tobacco should be avoided during pregnancy and given to very young children with care, it appears that goldenseal is unlikely to be toxic in normal doses.  Interactions with drugs with narrow therapeutic windows like Warfarin, cyclosporin, protease inhibitors and cardiac glycosides are potential concerns,

# Cautions
According to Herbalist Paul Bergner,AHG, only 10% of goldenseal is used when it is appropriate and there are no better substitutes.  Goldenseal has an affinity for mucosa, and is cooling so should not be used if an infection is at an early stage or there are more chills than fever.  Goldenseal should be used with caution only while sick with illnesses that respond to hydrastine and berberine.  It should generally not be taken for an early stage URI, but reserved for illnesses in which there is yellow or green phlegm.  Generally a two week maximum dosage is suggested. Taking goldenseal over a long period of time can reduce absorption of B vitamins.   Avoid goldenseal during pregnancy and lactation, with gastrointestinal inflammation, and with 
proinflammatory disorders.

# No effectiveness for masking illicit drug use in urine drug tests
Goldenseal became a part of American folklore associated with chemical testing errors, from pharmacist John Uri Lloyd's 1900 novel Stringtown on the Pike where goldenseal is confused with strychnine.  It has been used on occasions in this century to attempt to mask the use of morphine in race horses (without success). 
Two studies have demonstrated no effect of oral goldenseal on urine drug assays over water alone. Subjects who drank large amounts of water had the same urine drug levels as subjects who took goldenseal capsules along with the water.  Because of the popular perception that this is true, drug tests will take the presence of hydrastine in the urine as likely proof that a person being tested is a drug user.

# Endangered status
Goldenseal is in serious danger due to overharvesting. Goldenseal became popular in the mid-nineteenth century. By 1905, the herb was much less plentiful, partially due to overharvesting and partially to habitat destruction. Wild goldenseal is now so rare that the herb is listed in the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) goldenseal is one of the most overharvested herbs. More than 60 million goldenseal plants are picked each year without being replaced.  The process of mountain top removal mining has recently put the wild goldenseal population at major risk due to loss of habitat, illegality of removing goldenseal for transplant without registration while destruction in the process of removing the mountain top is permitted, and increased economic pressure on stands outside of the removal area.  
There are several berberine-containing plants that can serve as useful alternatives, including Chinese coptis, yellowroot, or Oregon grape root. Many herbalists urge caution in choosing products containing goldenseal, as they may have been harvested in an unsustainable manner as opposed to having been organically cultivated.