Bloodroot

Bloodroot (Sanguinaria canadensis L.): A Comprehensive Reference

1. Identity, Nomenclature, and Botanical Description

1.1 Taxonomic Identity

Sanguinaria canadensis L. is a member of the Papaveraceae family. It is the only species in its genus within the poppy family (Papaveraceae). The genus name Sanguinaria is derived from the Latin word sanguis, meaning blood, while the species epithet canadensis indicates its Canadian origins. It is most closely related to Eomecon of eastern Asia.

1.2 Common Names and Synonyms

Other common names include bloodwort, Indian paint, puccoon, and red puccoon. Sanguinaria canadensis is also sometimes known as Canada puccoon, redroot, and black paste. The reference to "puccoon" is derived from the Powhatan word poughkone, which refers to several plants used by Indigenous people for dyes.

1.3 Geographic Distribution and Habitat

It is a native spring wildflower that grows in rich woodlands of North America from Nova Scotia to Florida and west to Alabama, Arkansas, Nebraska, and Manitoba. It can grow in full sun but is more often found in semi-shaded, light-wooded areas with moist, acidic soil. This species is found in undisturbed woodlands, on flood plains, and on slopes near streams or ponds in hardiness zones 3–8.

1.4 Morphological Characteristics

A perennial that grows up to 10 inches tall, the plant has a single basal leaf that can be as wide as 8 inches. The flower is located on a separate stalk and is white with a yellow center. Bloodroot is one of the first wildflowers to bloom, beginning in late winter and continuing into early spring. In its off-season, the plant remains dormant and can survive below-freezing temperatures.

The rhizomatous, herbaceous perennial has a red-orange rhizome which grows slightly below the soil surface. Bloodroot gets its colloquial name from its red sap, which is released when the plant's rhizome is cut. The reddish sap exudes from all parts of the plant, but especially the root, when cut.

1.5 Medicinal Part and Common Preparations

The rhizome of the plant, also known as bloodroot because of its red latex, contains a number of biologically active alkaloids that have been investigated as potential drug candidates. Historically and in contemporary commerce, bloodroot preparations have taken several forms:

• Dried rhizome and root powder: Used to produce natural red, orange, and pink dyes.
• Tincture and fluid extract (specific sanguinaria): Specific sanguinaria, the preparation principally employed by Eclectic physicians, has a deep ruby-red color and little odor.
• Toothpaste and mouthwash: The rhizome of Sanguinaria canadensis contains an active principle with antimicrobial, anti-inflammatory, antioxidative, and immunomodulatory effects, and for this reason S. canadensis extract has been added to toothpastes and mouthwashes in various concentrations.
• Escharotic salve ("black salve"): Most formulations of black salve include the primary ingredients of bloodroot (Sanguinaria canadensis) and zinc chloride and induce tissue necrosis, leading to eschar formation and subsequent tissue sloughing.
• Homeopathic preparations: Currently, the plant is used as a homeopathic remedy for menopausal flushing and osteoarthritis.
• Agricultural feed supplement: The plant is also used as an agricultural feed supplement.

2. Traditional and Historical Use

2.1 Native American Use

Sanguinaria canadensis, also known as bloodroot, is a traditional medicine used by Native Americans to treat a diverse range of clinical conditions. Native Americans used bloodroot in blood tonification and purification, wound healing, and pain and fever relief. Historically, parts of bloodroot were used by Native Americans to treat respiratory and gastrointestinal problems and to induce abortions in both people and horses.

Bloodroot was a traditional medicine used by many American Indian tribes to treat fever and rheumatism; other traditional uses were for treatment of ulcers, ringworm, and skin infections. Eastern American Indian tribes used it as a red dye and in the treatment of ulcers, skin conditions, and as a blood purifier. The juice was also used for coughs and sore throats, with the bitter taste masked by placing the juice on a lump of maple sugar that was then sucked.

Native Americans used bloodroot as a dye, love charm, and medicine. Bloodroot is a red natural dye used by Native American artists, especially among southeastern rivercane basketmakers. In some communities, the plant also carried ceremonial significance. In some Algonquin communities, bloodroot is associated with love, and men would wear bloodroot paint when they went courting.

2.2 Adoption by European Colonists and 19th-Century Western Medicine

European colonists adopted Native American medicinal uses to suit their own needs, and bloodroot was described in pharmacopoeias as early as the 1800s, with detailed descriptions of the plant, constituents, therapeutics, and case studies. Eclectic medicine practitioners and others learned from local Indigenous peoples, and by the early 19th century bloodroot was officially listed in the United States Pharmacopeia.

During the 19th century, bloodroot was adopted into American eclectic medicine, where it was classified as a stimulating expectorant and diaphoretic in smaller amounts. Eclectic physicians employed it as an ingredient in syrups and tinctures for bronchial and pulmonary complaints. Higher oral doses were observed to expel phlegm and cause vomiting, and the root entered 19th-century medicine as a caustic topical treatment for skin cancers, polyps, and warts.

An American surgeon, Jesse Weldon Fell, learned of the Cherokee Indians' use of bloodroot to treat cancer and found that zinc chloride enhanced its action; Fell pioneered the combination of these two agents into a cancer salve first reported in the medical literature in The Lancet in 1857, and similar topical treatments known as black salve remain in use today.

Historical information on the use of bloodroot can be found in William Barton's Vegetable Materia Medica written in 1818. The popular use of herbal remedies declined in the 1920s with the development of the pharmaceutical industry, though there has been a renewed interest in herbal medicine as research confirms the efficacy of some traditional uses.

2.3 20th-Century Dental Applications

In 1983, an extract of bloodroot was marketed in toothpastes and mouthwashes for prevention of gum disease and plaque; however, the sanguinarine-containing oral rinse product Viadent was subsequently withdrawn from the market in North America due to increased risk of developing oral leukoplakia.

3. Phytochemical Composition and Active Constituents

3.1 Primary Alkaloid Classes

S. canadensis contains eight isoquinoline alkaloids at biologically relevant concentrations, including six quaternary benzophenanthridine alkaloids (QBAs) — sanguinarine, chelerythrine, sanguilutine, chelilutine, sanguirubine, and chelirubine — and two protopin alkaloids, protopine and allocryptopine.

The S. canadensis rhizome was found to contain an alkaloid pool consisting of the major QBAs sanguinarine (36.5%) and chelerythrine (33.4%), and the minor QBAs sanguilutine (9.1%), chelilutine (7.8%), chelirubine (2.5%), and sanguirubine (1.2%); in addition, the protopin alkaloids protopine (4.1%) and allocryptopine (4.2%) and trace amounts of the protoberberine alkaloids berberine and coptisine (0.1%) were also identified.

Subsequent studies analyzing rhizome alkaloid composition in wild US populations have shown considerable natural alkaloid variation. This variation has significant implications for the consistency of bloodroot-derived preparations.

3.2 Sanguinarine: The Principal Alkaloid

Sanguinarine is a benzophenanthridine alkaloid derived from rhizomes of Sanguinaria canadensis L. (bloodroot); it is a cationic molecule which converts from an iminium ion form at pH less than 6 to an alkanolamine form at pH greater than 7. Chemically designated as 13-methyl-[1,3]benzodioxolo[5,6-c]-1,3-dioxolo[4,5-I]phenanthridinium, it is present not only in bloodroot but also in Chelidonium majus L. and the seeds of Argemone mexicana L.

3.3 Chelerythrine

Chelerythrine is the second most prevalent alkaloid in S. canadensis, having two methoxyl substituents at the C11 position on the aromatic D ring. Sanguinarine and chelerythrine are the major quaternary benzophenanthridine alkaloids present in S. canadensis.

3.4 Dye Constituents

The plant is used to produce natural red, orange, and pink dyes from the rhizome. Bloodroot gets its colloquial name from its red sap, which is released when the plant's rhizome is cut, and this sap contains a high concentration of alkaloids that are used by the plant for protection against predators.

4. Mechanisms of Action

4.1 Antimicrobial Action

Sanguinarine has broad antimicrobial activity as well as anti-inflammatory properties; in vitro studies indicate that the anti-plaque action of sanguinaria is due to its ability to inhibit bacterial adherence to newly formed pellicle, its retention in plaque being 10–100 times its saliva concentration, and due to its antimicrobial properties; the MIC of sanguinarine ranges from 1 to 32 micrograms/mL for most species of plaque bacteria.

As a group, the benzophenanthridine and protopin alkaloids of S. canadensis have significant antimicrobial action; sanguinarine has been found to induce the release of bacterial membrane-bound cell wall autolytic enzymes.

4.2 Anticancer and Cytotoxic Mechanisms

Sanguinarine exerts several biological activities including antimicrobial, antioxidant, anti-inflammatory, as well as anticancer properties. Multiple overlapping mechanisms have been identified in preclinical studies:

• Apoptosis induction via reactive oxygen species (ROS): Sanguinarine treatment resulted in concentration-response growth inhibition of bladder cancer cells by inducing apoptosis; this apoptosis was correlated with the up-regulation of Bax, the down-regulation of Bid and XIAP, the activation of caspases -3, -8, and -9, and the generation of increased reactive oxygen species (ROS); the ROS scavenger N-acetyl cysteine completely reversed the sanguinarine-triggered apoptotic events.
• NF-κB inhibition: Sanguinarine is a powerful inhibitor of nuclear transcription factor NF-κB activation, which is important in the regulation of cell growth, cell cycle progression, and apoptosis.
• DNA intercalation: Laboratory studies suggest sanguinarine has potential antineoplastic properties, as it intercalates with DNA at guanine-cytosine-rich sequences.
• Antiangiogenic effects: Tumor growth facilitated by neovascularization is another area targeted by sanguinarine; at nanomolar concentrations, it inhibits vascular endothelial growth factor A (VEGF-A) induced endothelial cell migration, sprouting, and survival.
• Ferroptosis: In human cervical cancer cells, sanguinarine efficiently activates both apoptosis and ferroptosis simultaneously, with ROS — specifically H2O2 — playing a central mediating role.
• NF-κB/ERK1/2 pathway suppression in breast cancer: Sanguinarine remarkably inhibited the inflammatory mediator chemokine CCL2 in triple-negative breast cancer cell lines, with mRNA CCL2 repression concurrent with reduction of its main regulator IKBKE and NF-κB signaling pathway proteins.

Sanguinarine targets a range of cellular structures and molecular processes; however, the contribution of each mechanism to the alkaloid's cytotoxicity and anticancer action is not clearly understood.

4.3 Non-Selective Cytotoxicity

The alkaloids of S. canadensis are nonspecific in their cytotoxicity, damaging both neoplastic and healthy tissue. In vitro studies of sanguinarine suggest it causes indiscriminate destruction of healthy and cancerous tissue at doses higher than 5 µM, limiting its practical utility.

4.4 Anti-inflammatory Mechanisms

Antiplaque effects may be caused by conversion of sanguinarine to an iminium ion that binds to plaque. Sanguinarine exerts antioxidant and anti-inflammatory properties alongside its antimicrobial activity.

5. Scientific Evidence by Area of Use

5.1 Dental Plaque and Gingivitis

The oral health application of bloodroot extract attracted the most substantial human clinical investigation, primarily during the 1980s and 1990s.

A review of clinical trials testing the regimen use of sanguinaria products for periods ranging from 14 days to six months established the clinical efficacy of the two products in combination, with the regimen approach producing consistently positive reductions in plaque, gingival inflammation and bleeding parameters for up to six months with no adverse hard tissue effects and only one reversible adverse soft tissue effect observed among the 260 subjects tested. One controlled clinical trial (14 weeks) found that sanguinarine-containing toothpaste and oral rinse significantly inhibited the redevelopment of gingivitis following a chlorhexidine phase; sanguinarine leads in some cases only to a transient burning sensation and could be used on a long-term basis.

However, more rigorous assessments produced conflicting and generally unfavorable conclusions. A systematic review concluded that when tested separately, neither the toothpastes nor the mouthwashes with S. canadensis extract had any demonstrable clinical effectiveness against dental plaque and gingivitis; although using them together twice a day seemed more effective than using placebo, more recent studies have shown conflicting results. Studies have found bloodroot-containing products inferior to drugs such as doxycycline and chlorhexidine, with concerns about safety.

Evidence strength: Mixed and ultimately negative. Earlier trials showed modest combination effects, but independent evaluation found no demonstrable effectiveness for either product used alone. The product was subsequently withdrawn from the North American market due to safety concerns (see Section 7).

5.2 Cancer — Topical (Black Salve)

S. canadensis cancer salves have a controversial history and have never been assessed in a clinical trial. Clinical trials in this area are lacking, with most clinical data in the form of case reports demonstrating suboptimal therapeutic and cosmetic outcomes associated with its use.

There are no studies evaluating its safety or efficacy for skin cancer, but cases of toxicity and lack of efficacy have been reported; in one case series, 3 of 4 cases presented with recurrence of basal cell carcinoma after self-treatment with black salve; while the black salve resulted in what appeared to be clinical responses in 2 of the cases, residual tumor was identified by biopsy; in one case, black salve caused a large keloidal scar that the patient sought to have surgically removed.

In vitro, sanguinarine was the most cytotoxic compound tested, with a 24-hour IC₅₀ of 2.1 µM against the A375 melanoma cell line and 3.14 µM against the A431 squamous cell carcinoma cell line; all black salve constituents showed greater in vitro cytotoxicity against the two skin cancer cell lines than the therapeutic comparator 5-fluorouracil. Chelerythrine and minor QBAs present in black salve, at concentrations not having a cytotoxic effect by themselves, boosted the cytotoxic effects of sanguinarine.

Bloodroot extracts have been promoted by some dietary supplement companies as a treatment or cure for cancer, but the U.S. Food and Drug Administration listed some of these products among its "187 Fake Cancer 'Cures' Consumers Should Avoid."

Evidence strength: Preclinical only (in vitro and in vivo animal data). No clinical trials exist. Available human data are limited to case reports demonstrating toxicity, treatment failure, and disfigurement. No conclusions regarding efficacy can be drawn.

5.3 Cancer — Systemic/Anticancer Properties of Sanguinarine

The cytotoxicity of sanguinarine against tumor cells has been reported in vitro and in vivo; furthermore, sanguinarine induced apoptosis and triggered cell death signaling cascades in numerous cancer cell lines. Despite their identification over 50 years ago, the alkaloids of S. canadensis have not been developed into successful therapeutic agents.

The major constituent of bloodroot, sanguinarine, exhibits antimicrobial, tumoricidal, anticancer, antiangiogenic, and antimicrotubule properties; however, its efficacy has not been tested in humans.

Evidence strength: Preclinical only. All anticancer evidence for sanguinarine as a systemic agent derives from cell culture and animal studies. No human clinical trials of systemic bloodroot or sanguinarine as a cancer treatment have been conducted.

5.4 Respiratory Conditions

Bloodroot was used historically by Native Americans for curative properties as an emetic, respiratory aid, and other treatments. Internally, it served as an expectorant for respiratory ailments, including coughs, sore throats, and bronchitis, by helping to clear mucus and ease breathing. The present principal use of sanguinaria historically was as a stimulant expectorant in cough syrups.

Evidence strength: Traditional use only; no controlled clinical trials have been conducted in humans for respiratory indications.

5.5 Homeopathic Use: Menopausal Flushing and Osteoarthritis

Currently, the plant is used as a homeopathic remedy for menopausal flushing and osteoarthritis. No peer-reviewed clinical trial evidence from the sources retrieved supports efficacy for these indications at homeopathic dilutions.

Evidence strength: No verified clinical trial evidence found in the literature reviewed.

5.6 Anti-Inflammatory Effects

Bloodroot has been used in medicine historically for its antimicrobial, antihypertensive, anti-inflammatory, and antineoplastic properties. Preclinical research has elucidated several inflammatory pathways targeted by sanguinarine. Sanguinarine has been shown to have anticarcinogenic and anti-inflammatory properties in experimental animals and may affect the degranulation and phagocytosis of neutrophils in vitro.

Evidence strength: Preclinical (cell culture and animal) only; no human clinical trials specifically assessing anti-inflammatory endpoints for bloodroot have been identified in the sources reviewed.

6. Body Systems and Health Areas Associated with Bloodroot

• Oral / Dental: Anti-plaque, anti-gingivitis properties (clinical trials conducted; results conflicting; product withdrawn from market due to leukoplakia risk)
• Dermatological / Integumentary: Topical escharotic for skin lesions and cancers (case reports only; significant toxicity documented)
• Oncological: Preclinical anticancer activity via multiple mechanisms (no human trials)
• Respiratory: Traditional expectorant and antitussive use (no clinical trial evidence)
• Gastrointestinal: Traditional use as an emetic and purgative; the rhizome of the plant is a local irritant which, in relatively mild doses up to toxic quantities, produces epigastric burning with vomiting, tormenting thirst, faintness, dimness of vision, vertigo, and alarming prostration.
• Cardiovascular / Blood: Traditional use as a blood purifier; preclinical antihypertensive effects noted
• Musculoskeletal: Homeopathic use for osteoarthritis (no clinical trial evidence)
• Endocrine / Reproductive: Homeopathic use for menopausal flushing; historical abortifacient use
• Agricultural / Veterinary: Some animal food additives sold and distributed in Europe contain sanguinarine and chelerythrine.

7. Dosage Forms and Reported Dosages

The following dosages are reported directly from the cited literature and refer only to the forms and quantities that appeared in scientific or clinical contexts. They are not recommendations.

• Oral rinse (dental use): A sanguinarine-containing mouthrinse, assessed in a 14-week controlled clinical trial, was used as part of a regimen with toothpaste after scaling and root planing; the preparation leads in some cases only to a transient burning sensation. Clinical trials have tested sanguinaria-containing oral hygiene products for periods ranging from 14 days to six months.
• Oral emetic dose: In doses of about 1 gram, the rhizome acts as a violent emetic.
• In vitro anticancer concentrations: Human lung cancer cells (A549) were treated with 4 µM of sanguinarine in one in vitro study. Sanguinarine is toxic to cervical cancer cells (HeLa) with a 50% inhibitory concentration (IC₅₀) of 0.8 µg/mL in vitro.
• Antibacterial MIC (in vitro): The MIC of sanguinarine ranges from 1 to 32 micrograms/mL for most species of plaque bacteria.
• Cytotoxicity threshold (in vitro): In vitro studies suggest sanguinarine causes indiscriminate destruction at doses higher than 5 µM.

Many factors have been shown to influence plant alkaloid concentrations, which may impact the alkaloid composition of current bloodroot therapeutics.

8. Safety, Toxicity, and Notable Interactions

8.1 Intrinsic Toxicity of Sanguinarine

The alkaloid sanguinarine is toxic, causing the death of animal cells, and ingesting it can cause the disease epidemic dropsy. In bloodroot, the sap is red and poisonous; products made from sanguinaria extracts, such as black salve, are escharotic and can cause permanent disfiguring scarring; if applied to the skin, the extract sanguinarine may cause a massive scab of dead flesh where it killed the cells, called an eschar.

8.2 Oral Leukoplakia and Carcinogenic Potential

Oral use of products containing bloodroot is strongly associated with the development of oral leukoplakia, which is a premalignant lesion that may develop into oral cancer, although one review disputed this finding. Based on epidemiological studies, there is a correlation between the use of toothpastes containing sanguinarine, an alkaloid derived from bloodroot, and development of oral leukoplakia (a possible precursor to oral cancer).

The alkaloids in black salve have also been shown to cause skin erosions and cellular atypia; bloodroot was once used as a mouth rinse and toothpaste to treat gingivitis, but this application was later associated with oral leukoplakia, a premalignant condition; leukoplakia associated with S. canadensis extract often is unremitting. Immediate discontinuation of the offending agent produces little regression, suggesting that cellular damage is irreversible.

Viadent, a dental product containing bloodroot, was withdrawn from the North American market due to concerns about its potential to cause cancer.

The association of S. canadensis-containing mouthwash with the development of leukoplakia and a murine model suggesting sanguinarine acts as a tumor promoter highlights the urgent need for studies into black salve carcinogenesis.

8.3 Dermatological Toxicity from Escharotic Use

Topical use of bloodroot for skin cancer can lead to severe adverse effects including disfigurement. Disfigurement and worsening lesions have been reported with topical use of bloodroot salves to treat skin lesions, with some cases requiring hospitalization; permanent scarring and disfigurement have also followed use of products containing bloodroot for removing skin moles/tags.

Despite increasing popularity among patients, black salve lacks clinical evidence supporting its efficacy and is associated with significant adverse events, including severe tissue destruction, secondary infection, and delayed medical treatment; when black salve is used to treat malignancies, patients may experience incomplete tumor eradication, which may also complicate treatment plans.

Use of bloodroot as an escharotic agent in the form of a salve or paste has led to localized tissue damage and disfiguring scarring in case reports.

8.4 Systemic Toxicity

The rhizome of the plant has not found favor in more modern times since sanguinaria is a local irritant which, in relatively mild doses up to toxic quantities, produces epigastric burning with vomiting, tormenting thirst, faintness, dimness of vision, vertigo, and alarming prostration. In doses of about 1 gram it is a violent emetic.

8.5 Glaucoma Contraindication

Bloodroot should be avoided in patients with glaucoma.

8.6 Regulatory Actions

Although regulators have issued warnings regarding black salve and have criminalized its importation in some jurisdictions, the therapy remains popular with patients interested in complementary and alternative medicine. Despite regulation, it can be illegally or surreptitiously purchased, usually online, and is marketed as an alternative medicine for treating various benign and malignant skin conditions.

8.7 Carcinogenic Potential — Unresolved

Sanguinaria canadensis, a major ingredient of black salve formulations, contains a number of bioactive phytochemicals including the alkaloid sanguinarine; despite its prolonged history of clinical use, conflicting experimental results have prevented the carcinogenic potential of sanguinarine from being definitively determined.

8.8 Variability of Alkaloid Content

Many factors have been shown to influence plant alkaloid concentrations, which may impact the alkaloid composition of current bloodroot therapeutics. The natural variation in S. canadensis alkaloids may offer an explanation for differing black salve clinical effects. This variability means that the potency and potential toxicity of any given preparation cannot be reliably predicted from the label or appearance alone.

9. Conservation Status

Today, literally tons of bloodroot are wildharvested every year. Many residents of southern Appalachia are buying bloodroot as ornamental plants in home landscaping, and prices for this botanical continue to trade in a low to medium price range compared with other medicinal herbs. Sustained commercial wildcrafting pressure raises conservation concerns for this woodland species.

10. Current Research Status and Pharmaceutical Development

Despite their identification over 50 years ago, the alkaloids of S. canadensis have not been developed into successful therapeutic agents; instead, they have been associated with clinical toxicities ranging from mouthwash-induced leukoplakia to cancer salve necrosis and treatment failure. Both the traditional use and modern biological investigations of bloodroot suggest it warrants further study as a phytochemical extract and as a source of individual alkaloid lead compounds.

Despite their elucidation over 50 years ago, and significant activity in a range of molecular pathways, the individual alkaloids of S. canadensis are yet to find utility as proven human therapeutics.

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