Sanguinaria canadensis

Blood root

Description

Bloodroot (Sanguinaria canadensis), of the Papaveraceae (poppy) family, is a small perennial herb (up to 0.4 m), producing a red sap or latex. It has solitary leaves and flowers emerging from a creeping, fleshy, red rhizome. The leaf has a rounded, markedly lobed blade. The attractive flower has four to 16 white petals and develops into a narrow, two-valved capsule containing numerous small seeds. Bloodroot is indigenous to North America and it is mainly wild harvested in the eastern part of the USA.1 The medicinal plant part used is the dried rhizome which has a slight odour and acrid and bitter taste.2 Other common names include Indian paint, tetterwort, red root, Paucon, Pauson, snakebite and sweet slumber.3

Constituents

Bloodroot contains up top 9% isoquinoline alkaloids, with sanguinarine (a morphine-like alkaloid) being the main compound accounting for about 50% of the alkaloid content, chelerythrine, sanguilutine, allocryptopine, protopine, berberine and coptisine.1 Sanguinarine and chelerythrine, although themselves colourless, form red and yellow salts, respectively. The rhizome also contains red resin and starch.2

Pharmacological activities

The documented activities of bloodroot are mainly ascribed to the actions of sanguinarine. It intercalates DNA (DNA intercalators are used in chemotherapeutic treatment to inhibit DNA replication in rapidly growing cancer cells), binds to proteins (including various receptors) and shows anti-inflammatory, antifungal, antimicrobial activity and antioxidant activity.1

Anticancer

Experimental studies with sanguinarine have been shown it to have several difference anti-cancer properties. Sanguinarine has been shown to have cytotoxic and DNA damaging effects against mouse leukemic cells and primary mouse spleen cells in vitro4, induce apoptosis.5-7, 7 and reduce angiogenesis.8, 9 Sanguinarine has been shown to inhibit proliferation of several types of human cancer cell including multidrug-resistant cells, whereas it has minimal cytotoxicity against normal cells such as neutrophils and keratinocytes.10 Other cancer types for which sanguinarine has been shown to be active includes breast and prostate cancer cell lines. It appears that sub-apoptotic concentrations of sanguinarine can suppress breast cancer cell proliferation for extended lengths of time, and that this effect results from a relatively brief period of activity when the drug is concentrated in the nucleus. Sanguinarine transiently inhibits DNA synthesis and disrupts cell cycle regulation and progression.11 Sanguinarine has also been shown to cause cell cycle blockade and apoptosis of human prostate carcinoma cells via modulation of cyclin kinase inhibition.12 The development of multidrug resistance (MDR) is a major obstacle to the success of chemotherapeutic agents. One problem is the multidrug resistance of the papilomarivus. Sanguanarine has been shown to be an effective against endocervical multidrug resistant human papillomavirus (HPV).13

However, an in vivo study found that sanguinarine did not significantly affect the distribution of cells among the different phases of the cell cycle. Singuinarine was evaluated in mouse bone marrow cells for its ability to induce clastogenicity (breaking of chromosomes) and DNA damage. The reduction in proliferation was statistically non-significant. This indicated that the alkaloid was not cytotoxic to the bone marrow cells at the doses tested.14

Topical application of sanguinarine, either as a pretreatment (30 min prior to UVB radiation) or post-treatment (5 min after UVB), resulted in a significant decrease in UVB-mediated increases in skin oedema, skin hyperplasia and infiltration of leukocytes. Further, sanguinarine treatments (pre and post) also resulted in a significant decrease in UVB mediated generation of the free radical H2O2 and increases in the protein levels of markers of tumor promotion and proliferation. Based on this data, the authors of this animal study suggest that sanguinarine could be developed as an agent for the management of conditions elicited by UV exposure including skin cancer.15

Cardiovascular effects

Sanguinarine has been shown in a hypertensive rat modul to decrease systolic blood pressure dose-dependently by up to 19%. Sanguinarine reduces blood pressure by decreasing angiotension receptor expression and by reducing aldosterone levels.16 Sanguinarine has also been shown to prolong ventricular refractoriness. This property may be useful in the treatment of ventricular arrhythmias.17

Sanguinarine has also been shown to produce a concentration-dependent positive inotropic effect in isolated, isometrically contracting left guinea pig atria. The effect was mediated via regulation of the sodium-potassium pump (inhibition of Na+,K+,ATPase activity).18 Positive inotropic agents increase myocardial contractility, and are used to support cardiac function.

Anti-inflammatory and Anti-platelet activity

Sanguinarine has been found to be a potent antiplatelet agent in vitro. It inhibited platelet aggregation induced by arachidonic acid (AA. Sanguinarine activates adenylate cyclase, inhibits platelet Ca(2+) mobilization, tromboxane production as well as suppresses COX-1 enzyme activity. Sanguinarine may have therapeutic potential for treatment of cardiovascular diseases related to platelet aggregation.19 Sanguinarine inhibits NF kappa B, reducing inflammation, viral replication and growth changes.3

Antibacterial

Sanguinarine is toxic to insects and vertebrates and inhibit the multiplication of bacteria, fungi and viruses. Sanguinarine inhibits choline acetyl-transferase, intercalates DNA, inhibits DNA synthesis and reverse transcriptase and affects membrane permeability.20 Sanguinarine has been shown to have antimicrobial activity against a range of bacteria including Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguis, Actinomyces viscosus and Actinomyces naeslundii.21 Sanguinarine has been shown to strongly induced filamentation in both Gram-positive and Gram-negative bacteria and prevented bacterial cell division by inhibiting cytokinesis.21

Methanol extracts of the rhizomes of bloodroot has been shown to inhibit the growth of Helicobacter pylori in vitro. Sanguinarine was shown to be the active compound.23 and a crude methanolic extracts blood root has been found to have significant antimycobacterial activity against Mycobacteroum aurum only (MIC=62.5 microg/ml). Bioassay guided fractionation led to the isolation of two known benzophenanthridine alkaloids, sanguinarine and chelerythrine, from bloodroot with chelerythrine being the most potent.24

Sanguinarine may also be antimicrobial by reducing lipase activity in the skin. It is known that certain microorganisms produce extracellular lipase to better colonize the skin and mucosal surfaces. Berberine and a number of structurally related alkaloids such as chelidonine, chelerythrine, and sanguinarine to inhibit lipase activity.25

Antioxidant activity

Sanguinarine is a strong antioxidant, affecting the activity of NADPH oxidase directly.26

Expectorant activity

The expectorant and emetic activity is probably due to the alkaloids causing irritation of the vagus nerve.1

Therapeutic activities

Actions

The BHP lists the actions as expectorant, spasmoplytic, emetic, cathartic, antiseptic, cardioactive.27

Bloodroot has a gentle but reliable cholagogue action.28

Traditional usage

William Cook, in The Physiomedical Dispensatory from 1869, writes that the dried root is a slow relaxant and stimulant, influencing the mucous membranes, gall-ducts, and secreting organs in general. Small doses of bloodroot were used to arouse the stomach slowly in atonic dyspepsia, act moderately upon the gall-ducts, and promote expectoration in low coughs.29 Bloodroot was considered a gentle but reliable cholagogue, used where the bile is deficient or vitiated and the general circulation feeble, with cold extremities and in sick headache, catarrhal jaundice.28 Bloodroot was considered a specific for chronic sluggishness of the liver in patients with a bilious temperament, and for chronic jaundice. It was not a herb the old herbalists used in sensitiveness or irritability of any mucous membrane or other part, but only in sluggish conditions.29 Bloodroot was also used for its alterative effect on the blood.30

It was also considered useful for bronchial or tracheal irritation, bronchial coughs, membranous and spasmodic croup, coughs and colds.30 where it resembles lobelia in action. It was thought to normalize the secretions, restoring the bronchial secretions when scanty and restraining them when profuse. It was specifically indicated when chilliness is a dominant feature of respiratory disorders, and is further indicated by burning and itching of the naso-laryngeal tract, tickling or burning in the nasal passages, with super-abundant secretion, irritation and tickling provoking cough.28 It was often combined with golden seal for chronic catarrh and nasal polypus, as a snuff, if the parts are freely discharging and are not too sensitive. This sounds like quite a heroic measure as the powder, when inhaled, is exceedingly irritating to the membranes, provoking violent sneezing, and free and somewhat prolonged secretion of mucus.29

It was also used for its ability to increase pelvic circulation, especially in females. As an emmenagogue it was considered of value where there is fullness of circulation.30 Bloodroot was used in amenorrhea in anemic and chlorotic patients who suffered with chills and headache, and in dysmenorrhea in debilitated subjects. It was also used for sexual debility, seminal incontinence and impotence dependent upon such conditions and relaxed genital organs.28

Externally, a vinegar tincture and water tincture of bloodroot was mixed with rose water was used as a wash for ringworm, eczema and pimples on the face.29

The BHP lists the following indications: Bronchitis, sub-acute or chronic. Asthma, croups, laryngitis, pharyngit. Deficient capillary circulation. Nasap polypus - as snuff. The specific indication is for asthma and bronchitis with feeble peripheral circulation.

Indications

Gastrointestinal system

Dyspepsia, poor appetite, sluggish liver, jaundice often associated with feeble circulation and cold extremities. May be effective against Helicobacter pylori, Candida albicans and other micro-organisms.

Respiratory system

Traditionally used for bronchitis, cough, croup and sore throats. The Eclectics used it for upper respiratory infections with a sense of constriction, burning, uneasiness, tickling or dryness of throat, nasal catarrh with little or no discharge30 and for harsh, dry cough with relaxed tissues of the pharynx, larynx and bronchi, with a sense of constriction and constant irritation and uneasiness or tickling in the throat.31

Oral hygiene

Plaque, a causal factor for caries and periodontal diseases, is a habitat for various microorganisms. predominantly Streptococcus mutans. Plaque removal (plaque control) is the most important measure for prevention of caries and gingivitis. Since mechanical removal of plaque is not adequate, chemical agents may also be used.32

Bloodroot is used in toothpaste and as a mouth rinse for plague and gingivitis. Commercial products containing 0.03-0.075% sanguinarine are considered safe and effective. More than 30 studies have examined the effectiveness of sanguinarine in the treatment of gingivitis and plague. Although the quality of the studies are varied, at least one very high quality study indicates that the alkaloid may be helpful in reducing these problems.33

Females disorders

Dysmenorrhoea where it increases pelvic circulation.30

Skin disorders

Externally, a vinegar tincture and water tincture of bloodroot was mixed with rose water was used as a wash for ringworm, eczema and pimples on the face.29

Externally it may also be used as a paste or ointment in the treatment of warts, skin tags, solar keratosis, fungal infections, eczema and possibly skin cancer.

There are numerous websites dedicated to a product based on bloodroot for various skin cancers. Bloodroot is also an ingredient in the paste developed by Hoxsey. Dr Weil writes that although Hoxsey's paste has never been formally studied, conventional doctors have used an identical one, sometimes in combination with surgery, to successfully remove skin cancers. It is a mixture of bloodroot and zinc chloride and is known as 'Mohs chemosurgery,' after Frederick Mohs, M.D., who invented the technique. A report by two dermatologists described the cases of four patients who had tried the pastes on their own. One appeared to have a complete cure, but a biopsy showed residual tumor. Another patient got rid of his skin cancer but was severely scarred in the process. A third was lost to follow up, and a fourth appeared to have cured his nasal basal cell carcinoma for several years, but the cancer recurred, requiring extensive surgery. Dr Weil have followed one case of an elderly man who used bloodroot paste successfully to remove a skin cancer on the scalp that had recurred after surgery. Dr Weil recommends the following method for removing skin tags or moles: Apply the powdered herb or as a paste, to the growth and then cover with a bandage. Repeat this for three days, washing the area with hydrogen peroxide before each new application. The paste will cause intense inflammation at the base of the growth, which usually turns pale, then falls off, leaving a very minimal scar and no damage to normal tissue. Dr Weil writes that he has the seen bloodroot paste do a better job with moles in difficult places than conventional surgery.34

Warning

In 2005, legal action was taken against a natural health practitioner in the US for prescribing bloodroot cream to several women with breast cancer who suffered disfigurement and tissue damage after using the cream.33

Use in pregnancy

No scientific information available. Considered safe to use during pregnancy by the early herbalists.

Toxicity

Sanguinarine is toxic in large doses, causing vomiting, diarrhoea, prostration and severe respiratory distress. The acute oral LD50 is 1,658 mg/kg for pure sanguinarine chloride. The dermal LD50 is greater than 200mg/kg.33

Contraindications and cautions

Bloodroot is a low dose herb. Like lobelia, bloodroot was in the past used as an emetic to cure respiratory problems including asthma. The current use of bloodroot is in sub-emetic dosages (less than 0.3 g or about 1 ml of a 1:3 liquid extract) which is safe and without significant adverse reactions. However, in excessive doses bloodroot is a gastric irritant, and a depressant; it produces burning and racking pains in the digestive canal from the mouth to the stomach; insatiable thirst, dilated pupils, nausea, an anxious countenance, coldness of the extremities, cold sweats and diminution of the pulse.

The use of pure sanguinarine in mouth rinse formulations may be associated with an increased risk of developing lesions known as leukoplakia. Researchers examined 148 people diagnosed with leukoplakia lesions in 1997 and 1998, and compared them with 148 people who did not have leukoplakia. Each patient was asked about tobacco use, alcohol use and the use of Viadent products which contains sanguinarine. Tobacco and alcohol use both are linked to the development of leukoplakia, which can lead to oral cancer. The study suggested that people who had used Viadent products were 9.7 times more likely to have been diagnosed with leukoplakia than with people who had not used the products.35, 36 However, a critique of the report by Damm et al maintains that it does not fulfill criteria for establishing causation. In particular, the study does not show that exposure to Viadent preceded the onset of leukoplakia, it does not demonstrate dose-response or biological plausibility, and it suffers from selection and information bias and from potential confounding. Furthermore, upon critical evaluation, the report on a case-series is inconsistent with the weight of available clinical evidence showing that Sanguinaria extract-containing oral health care products cause no cytotoxic or significant irritant effects in the oral mucosa in human studies of up to 6 months duration. The animal data similarly do not support a causal association between Viadent usage and oral leukoplakia in humans. These data demonstrate that Sanguinaria extract and whole Viadent formulations are without significant irritation potential and have no effects on the oral mucosa, even in studies with life-long dietary exposure to Sanguinaria extract. The mutagenicity and genotoxicity data do not indicate that Sanguinaria extract or its components are genotoxic in vivo. The results of 2 GLP-compliant rat oncogenicity studies provide no evidence of any carcinogenic effect of Sanguinaria extract. In conclusion, the available clinical and animal data provide no support for and in fact argue strongly against the hypothesis that the use of Viadent toothpaste and/or oral rinse products may be causally associated with the development of leukoplakia in humans37 However, a more recent study also proposes a connection between Viadent products and increased risk of oral leukoplakia.38

An even more serious toxicity has been reported in India where epidemic dropsy resulted from the consumption of edible oils adulterated with Argemone mexicana oil by unscrupulous traders. The liver, heart, kidney and lungs are the major target organs of the toxins (the alkaloids, sanguinarine and dihydrosanguinarine) and damage is mostly caused by free radical (singlet oxygen and hydroxyl radical) to the cell membranes. The illness starts as a gastro-enteric illness followed by oliguria and pedal oedema, cutaneous erythema, pigmentation of the skin; shortness of breath with orthopnoea; right-sided heart failure with normal left ventricle functions; as well as severe anaemia and hypoalbuminaemia.39;40

Not recommended for children due to risk of overdosing.

Drug interaction

There are no published reports about specific drug interaction, however, bloodroot should be used with caution with any morphine-like medication causing CNS sedation and low blood pressure.33

Dosage and administration

Blood root is used internally as an infusion or liquid extract or externally as an ointment. It is sometimes given as a daily dose, but was frequently prescribed by the Eclectics and Physiomedicalists in smaller, divided dosages. Do not prescribe above the recommended maximum dose.

Dried rhizome

0.06-0.5 g three times daily27

Liquid extracts

1:1 in 60% alcohol, 0.06-0.3 ml three times daily27
1:3 60% alcohol - 0.2 to 1.0ml three times daily

Reference List

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