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| EVIDENCE FOR EFFICACY (HUMAN DATA) |
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Clinical Trials
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After periodontal planing, 30 patients using sanguinarine-containing toothpaste and rinse had 32% fewer bleeding sites after 14 weeks compared with those using control toothpaste and rinse
Tenenbaum 1999
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Doxycycline was superior to sanguinarine for periodontitis in metaanalysis of 3 studies with 1002 patients
Drisko 1998
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Dentifrice and oral rinse containing sanguinaria & ZnCl gave no significant advantage in periodontal condition in a small study of 34 people
Cullinan 1997
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5% sanguinarium was not as good as scaling and root planing for periodontitis in a study with 201 patients
Polson 1996
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Review about sanguinarine mouthwashes indicates it has some benefit but is less effective than chlorhexidine
Grenby 1995
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Review indicates the quaternary ammonium compounds and sanguinarine compounds (Viadent) have some merit, but studies of their efficacy in plaque and gingivitis reduction are mixed
Mandel 1994
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Dentifrice with 0.075% sanguinaria extract and 2% ZnCl2, in a study of 120 peole for 6 months, lowered gingival inflammation 17%. 0.8% sodium monofluorophosphate gave added improvement
Kopczyk 1991
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Gram-negative counts in supragingival plaque decreased 83% in the group using dentifrice containing 0.075% sanguinaria & 2% ZnCl and increased 232% for the control group in a 6 month double blind study of 60 people
Harper 1990
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Review of clinical trials finds consistently positive reductions in plaque, gingival inflammation and bleeding parameters with no adverse hard tissue effects and only one reversible adverse soft tissue effect among the 260 subjects tested
Kuftinec 1990
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Gel containing 0.5% sanguinarine did not prevent plaque but did retard gingivitis. Chlorhexidine was superior
Kurbad 1990
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Review of clinical trials with Sanguinaria reveals improvements needed for future trials: parallel design, appropriate subjects and controls, sufficient subjects, proper statistical methodology
Laster 1990
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After 3 weeks of treatment the Plaque Index decreased 47.3% and Gingival Index 55.6% in handicapped children using a mouth rinse containing 0.03% sanguinaria extract
Miller 1990
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Viadent reduced plaque by 57%, gingival inflammation by 60%, and sulcular bleeding by 45% from baseline compared with placebo group 27%, 21% and increase of 30% in a 6 month study with 24 people
Hannah 1989
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No significant difference was found between the sanguinaria-ZnCl2 or the NaF dentifrices in a 21 day study with 59 people
Mallatt 1989
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No benefit was obtained with toothpaste containing 750 mcg/g sanguinaria extract in a 6 month double blind study with 120 adults
Mauriello 1988
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"Effects of sanguinaria extract on plaque retention and gingival health " (no abstract)
Miller 1988
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Viadent, containing 0.03% sanguinaria extract (0.01% sanguinarine chloride) and a 1000 ppm ZnCl2, failed to reduce plaque in a 3 week trial with 12 students
Etemadzadeh 1987
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300 micrograms/ml manual rinse or irrigation with 22.5 micrograms/ml sanguinaria reduced plaque 18% & 24% while water alone increased 52%, in a 2 week study with 44 people
Parsons 1987
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Plaque and gingivitis scores were lower with use of the sanguinaria-containing rinse and irrigating solutions compared with the placebo rinse in a 2 week study
Southard 1987
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Lower plaque scores were obtained with 300 micrograms/ml sanguinaria rinse in a week
Southard 1987
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Mouthrinse of a 0.03% aqueous solution of Sanguinaria extract reduced plaque in a 2 week trial with 14 students refraining from mechanical tooth cleaning
Wennstrom 1985
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Review concludes that oral rinses containing sanguinaria extract showed antiplaque activity in humans
Southard 1984
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10% doxycycline hyclate was superior to 5% sanguinarium in probing depth reduction at all timepoints in a 9 month study with 180 periodontitis patients--Polson; J Periodontol 1997 Feb;68(2):119-26
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Observational Studies/Case Reports
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Bloodroot has a long history of use in tinctures and expectorants in pharmaceutical products
Harkrader 1990
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"Sanguinaria in the control of bleeding in periodontal patients " (no abstract)
Klewansky 1986
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"Effect of 0.03% sanguinaria rinse on plaque and gingivitis when delivered as a manual rinse and under pressure in an oral irrigator " (no abstract)
Parsons 1986
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Adverse Effects & Toxicity
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"Viadent-related leukoplakia--the tip of the iceberg? " (no abstract)
Allen 1999
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A retrospective review of 88 patients with oral leukoplakia found that 84% of them had used Viadent, whereas the prevalence of use was only 3% in 100 randomly selected adults
Damm 1999
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Cytotoxicity of benzo[c]phenanthridines (e.g. fagaronine) is not seen with chelerythrine & sanguinarine; likely because they lose both the immonium region and molecular planarity
Nakanishi 1999
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Mustard oil contaminated with sanguinarine containing Argemone seeds was associated with a dropsy syndrome in Nepal
Singh 1999
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Symptoms associated with sanguinarine contaminated oil include vomiting, diarrhea, nausea, swelling of limbs, erythema, pitting edema, breathlessness. It decreases liver glycogen by activating glycogenolysis leading to high pyruvate. It inhibits ATPase
Das 1997
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24-hr midpoint (NR50) cytotoxicity to S-G gingival epithelial cells was 7.6 microM. Increasing pH to 7.8 increased potency, presumably due to the enhanced uptake of the lipophilic alkanolamine form compared to the cationic iminium
Babich 1996
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Glutamate decarboxylase (EC 4.1.1.15) of rat brain, a key step in GABA production, is inhibited by sanguinarine, with Ki 7.10(-4) mol/l and is irreversible
Netopilova 1996
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NMR indicates sanguinarine intercalates more deeply into DNA than berberine
Saran 1995
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Cytotoxicity of the benzo[c]phenanthridine alkaloids sanguinarine & chelerythrine on hepatocytes is dose (35-100 microM) and time (1-3 h) dependent
Vavreckova 1994
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Chelidonine, sanguinarine & chelerythrine (microM) inhibit taxol-mediated polymerization of rat brain tubulin. Sanguinarine inhibits both colchicine & podophyllotoxin binding to tubulin with I50 = 32 & 46 microM
Wolff 1993
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Expert Panel on Sanguinaria concluded that the data base on it is substantial and it is safe in its use in Viadent products and suggestions of toxicity is largely anecdotal
Frankos 1990
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No adverse effects on fertility nor teratogenicity in female rats & rabbits given 10-100 mg/kg/d but reduced egg implantation and offspring body weight was seen at the highest levels
Keller 1989
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"Sanguinarine and the controversy concerning its relationship to glaucoma in epidemic dropsy " (no abstract)
Lord 1989
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Acute oral LD50 in rats of sanguinarine was calculated to be 1658 mg/kg, and of the two alkaloid extracts, 1440 & 1250 mg/kg. No toxic effects were seen in rats fed up to 150 ppm sanguinarine in the diet for 14 days
Becci 1987
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"Questions on use of sanguinaria " (no abstract)
Keogh 1987
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"Safety profile of sanguinarine and sanguinaria extract " (no abstract)
Schwartz 1986
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A single i.p. dose (10 mg/kg) of sanguinarine increased the activity of SGPT and SGOT reduced microsomal cytochrome P-450 and benzphetamine N-demethylase activity. The rats lost body and liver weight and had peritoneal edema
Dalvi 1985
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The charged form of sanguinarine inhibits the ouabain-sensitive K -- Na pump but does not affect leakage of K and Na. The uncharged form causes lysis of red cells but does not inhibited the pump
Cala 1982
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Cardiac atria contractility was doubled by microM sanguinarine (comparable to ouabain). It completely blocks Na+,K+-ATPase at 100 microM. IC50 & ED50 are 6 microM
Seifen 1979
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Contraindications
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Serious consequences may result by usage of Zinc chloride and Sanguinaria canadensis (escharotic agents) that are used as part of the Mohs chemosurgery fixed-tissue technique; hence recommended against the use for skin cancer.
Mc Daniel 2002
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Animal Studies
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Veadent mouth rinse mildly inhibited S. sobrinus & S. mutans colonization on rat molars, but plaque formation by the combination of streptococci was not hampered
Altenhofen 1989
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Pharmacodynamics
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Min. inhibitory concentration (MIC) of macelignan (3.9 microg/ml ) against S. mutans was much lower than sanguinarine (15.6 microg/ml), eucalyptol (250 microg/ml), menthol &thymol (500 microg/ml) & methyl salicylate (1000 microg/ml).
Chung 2006
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Sanguinarine inhibits platelet aggregation induced by arachidonic acid (AA), collagen,U46619 and sub-threshold concentration of thrombin (0.05U/ml) with IC(50)concentrations of 8.3, 7.7, 8.6 and 4.4muM, respectively.
Jeng 2006
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Studies on bovine tooth enamel embedded in resin, polished, exposed to a lactate carbopol buffer system for 44 hours treated with dentifrices containing both NaF (fluoride) and SG (sanguinaria) showed a significantly greater effect on the remineralisation of the enamel lesion.
Hong 2005
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Sanguinarine treatment of LNCaP and DU145 cells for 24 hours resulted in dose-dependent inhibition of cell growth, arrest of cells in G0-G1 phase of the cell cycle, and induction of apoptosis suggesting as agent for the management of prostate cancer.
Adhami 2004
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Sanguinarine strongly suppresses basal and VEGF-induced Akt phosphorylation, while it did not produce any changes in VEGF-induced activation of ERK1/2 and PLCgamma1 suggesting it as a potent antiangiogenic natural product.
Eun 2004
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Dual inhibition of both LOX- and COX-metabolic pathways explains clinical efficacy and the favorable gastrointestinal tolerability of the original remedy Zeel comp. N. (containing mother tinctures of Arnica montana, Sanguinaria canadensis and Rhus toxicodendron.)
Jaggi 2004
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Sanguinarine [0.1 (M-2 (M)] treatment to immortalized human keratinocytes cells found to inhibit in a dose-dependent manner the cell proliferation and induce apoptosis, suggesting its usage in hyperproliferative skin disorders, including skin cancer.
Adhami 2003
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Sanguinarine chelerythrine and protopine, isoquinoline alkaloids (fractions of methanol extracts of the rhizomes of Sanguinaria Canadensis) show antibacterial activity against 15 strains of Helicobacter pylori.
Mahady 2003
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Crude methanolic extracts from plants C. mukul, P. corylifolia & Sanguinaria canadensis, showed antimycobacterial activity against Mycobacterium aurum only & sanguinarine & chelerythrine isolated from roots S. Canadensis. were effective against both Mycobacterium aurum & M. smegmatis.
Newton 2002
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Sanguinarine inhibits the binding of [3H]ouabain to microsomes prepared from yeast cells expressing the sodium pump with an IC50 of 94.5+/-4.3 microM, indicating that sanguinarine specifically targets the sodium pump.
Scheiner-Bobis 2001
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Repeated treatment of saliva-conditioned synthetic hydroxyapatite disks with green tea bioflavonoid/zinc ascorbate, sanguinarine/zinc chloride, or triclosan dentifrice resulted in significant reductions in total viable plaque biomass when compared to a non-active placebo control dentifrice.
Wolinsky 2000
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0.001% sanguinarium inhibits neutrophil chemotaxis, oxidative metabolism and degranulation within 5 min and is not lytic to neutrophils from peripheral blood or crevicular fluid, at all concentrations tested
Agarwal 1997
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NF-kappaB activation is suppressed by sanguinarine dose- and time-dependently in human myeloid ML-1a cells
Chaturvedi 1997
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Yeasts can survive in sanguinarine containing mouthrinse whereas they are killed in rinses containing cetylpyridinium or chlorhexidine
Giuliana 1997
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Chelerythrine and sanguinarine from Eschscholtzia bind rat liver vasopressin V1 receptors and are competitive inhibitors of vasopressin binding
Granger 1992
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MIC for sanguinarine were 4 - 8 micrograms/ml for Streptococcus and Actinomyces and synergized by Zn. Viadent oral rinse (300 micrograms sanguinaria extract/ml & 0.2% ZnCl (14.9 mM) inhibited all strains tested
Eisenberg 1991
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"The Sanguinaria story--an update and new perspectives (overview of the Toronto symposium) " (no abstract)
Nikiforuk 1990
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"Effects of sanguinarine and Sanguinaria extract on the microbiota associated with the oral cavity " (review, no abstract)
Walker 1990
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Review shows sanguinarine converts from an iminium ion form at pH <6 to an alkanolamine form at pH> 7. It retains in plaque at 10-100 times its saliva concentration. MIC for most plaque bacteria is 1-32 micrograms/ml
Godowski 1989
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"Effects of sanguinaria extract on leucocytes and fibroblasts " (no abstract)
Karjalainen 1988
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"Antimicrobial properties of sanguinaria, stannous fluoride and zinc chloride on the growth and acid production of Streptococcus mutans " (Spanish, no abstract)
Gomez 1987
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"Crevicular delivery of sanguinaria to control gingivitis " (no abstract)
Swanbom 1987
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"Antiplaque activity of a sanguinaria-containing oral rinse: an in vitro study " (no abstract)
Babu 1986
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"Longitudinal evaluation of sanguinaria: clinical and microbiologic studies " (no abstract)
Palcanis 1986
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Analytical Chemistry
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Quantitation of sanguinarine and chelerythrine, alkaloids from Sanguinaria Canadensis by capillary electrophoresis showed excellent linearity (R(2)>0.998), precision (RSD%=1.8%) and detection limit (2.4-3.0 microM).
Suntornsuk 2002
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The biosynthetic pathway of sanguinarine, morphine, berberine & tubocurarine from the tetrahydrobenzylisoquinoline alkaloid (S)-N-methylcoclaurine depends on a P-450-dependent mono-oxygenase
Pauli 1998
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Dihydrobenzophenanthridine oxidase, a 77-kD protein, identified by antibody label and distinguished from a 70 kD polyphenol oxidase
Ignatov 1997
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Dihydrobenzophenanthridine (DHBP) oxidase catalyses the last step of biogenesis of sanguinarine. It is stimulated by jasmonic or acetylsalicylic acid
Ignatov 1996
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Thermodynamics of sanguinarine binding to DNAs shows negative enthalpy changes and positive entropy changes
Sen 1996
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Quercetin or rutin induced sanguinarine and chelerythrine biosynthesis, dose-dependently, and is offset by calcium chelator or blocker. Baicalein, naringin, naringenin, catechin, caffeic acid & benzoic acid are very weak inducers
Mahady 1994
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Sanguinarine, 1-3% dry wt of S. canadensis rhizomes and a trace in Papaver bracteatum. In cell cultures it can be stimulated by Verticillium dahliae fungus
Cline 1993
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Purification of dihydrobenzophenanthridine oxidase (DHBPO) which oxidizes dihydrosanguinarine to sanguinarine, pH opt 7.0, Vmax = 27 nkat/mg protein, Km=6 microM for dihydrosanguinarine, 10 microM for dihydrochelerythrine
Arakawa 1992
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Sanguinarine is phototoxic to mosquito larvae, with an LD50 = 0.096 mg/mL with near UV exposure as compared with 23.3 mg/mL without. Sanguinarine is an efficient electron donor
Arnason 1992
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Fluorescence quenching of the alkanolamine form of sanguinarine increases with pH & decreases with temperature. This may be due to proton transfer from a 6-OH group to the lone pair of nitrogen through the formation of zwitterion
Das 1992
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Sanguinarine accounts for 80% of the total alkaloid. Other benzophenanthridine alkaloids are sanguilutine, sanguirubine, chelerythrine, chelilutine and chelirubine
Rho 1992
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Sanguinarine, chelerythrine, chelirubine, sanguilutine, protopine, allocryptopine and the isomers sanguirubine and/or chelilutine identified by FAB-MS
Bambagiotti-Alberti 1991
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HPLC analysis of sanguinarine with a detection limit of 3 ng
Reinhart 1991
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DNA intercalation of benzophenanthridines is pH dependent, being much greater below pH 7
Bajaj 1990
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"Detection and quantitative analysis of sanguinarine in edible oils " (no abstract)
Balderstone 1977
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"Biological and phytochemical evaluation of plants. 8. Isolation of a new alkaloid from Sanguinaria canadensis " (no abstract)
Tin-Wa 1970
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Pharmacokinetics (ADME)
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Chemistry and biochemistry of benzophenanthridine alkaloids found in Sanguinaria extract, incl. the dynamic equilibrium between acid and base forms, and pharmacokinetics of Sanguinaria extract when used as dentifrice or oral rinse formulation.
Harkrader 1990
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Genetics & Molecular Biology
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Investigation of genetic and environmental influences on alkaloid production using Sanguinaria canadensis as a model revealed that Genetic influences represented by clone effects may be indicated by variation in alkaloid concentration by clone.
Salmore 2001a
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Review about the potential of sanguinarine and ellipticine as DNA intercalating antitumor compounds
Faddeeva 1997
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DNA binding of sanguinarine measured by reflectometric interference spectroscopy
Piehler 1997
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Berberine and sanguinarine intercalate DNA and inhibit DNA synthesis & reverse transcriptase
Schmeller 1997
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Sanguinarine inhibits the catalytic subunit of cAMP-protein kinase (cAK) but weakly of protein kinase C, IC50=6 & 217 microM, respectively. Methylated sanguinarines are inactive on cAK
Wang 1997
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Sanguinarine & chelerythrine strongly inhibit aromatic amino acid decarboxylase (EC 4.1, 1.28) irreversibly with Ki 1.2 x 10(-4) M & 5.8 x 10(-4) M, respectively. Dithiothreitol prevents inhibition suggesting the importance of thiol groups
Drsata 1996
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Contemporary Formulas
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Benzophenanthridine synthesis by Sanguinaria cell culture is stimulated by Phorbol-12-myristate-13-acetate (65x), 1-oleoyl-2-acetyl-rac-glycerol (25x), cholera toxin (25x), G-protein activators, fungal elicitor and abscisic acid
Mahady 1998
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Patents
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Conduct a search on "sanguinaria" or "bloodroot" in the title, abstract or claims section of the
US patents database
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Mouthwash composed of echinacea, hydrastis canadensis, sanguinaria canadensis, quercus alba, grapefruit seed extract, aloe vera juice, water, vegetable glycerin, and peppermint oil;
US Patent 5,378,465
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Efficacy and stability of mouthrinses containing sanguinaria attained by adding a surfactant combination of an amidobetaine and poly(oxyethylene)-poly(oxypropylene) block copolymer;
US Patent 5,073,368
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Chewing gum containing either sanguinarine, benzophenanthridine alkaloid, or soluble poly-pyrophosphates, or both to chemically inhibit the formation of plaque and calculus;
US Patent 4,908,211
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Inhibition of histamine release from mammalian mast cells by sanguinarine, a benzophenanthridine alkaloid;
US Patent 4,737,503
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Periodontal paste of zinc chloride 45%; sanguinaria 10.8%; galangal 7.2%; water 37% (by weight);
US Patent 4,335,110
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Cultivation, Conservation & Ecology
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It is demonstrated that forest edges and Sanguinaria invicta invasion influence Sanguinaria canadensis seed dispersal destination and distance, respectively and these forces act independently.
Ness 2004
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Study of reproductive and vegetative characters in Sanguinaria canadensis along an elevational gradient over two growing seasons revealed that alkaloid content declines with elevation, increases with water content, varies by site, and fluctuates seasonally with plant growth and reproduction.
Salmore 2001b
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Sanguinaria canadensis info at
NewCROP
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| HISTORY OF RECORD |
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| RESEARCHED BY: Soaring Bear, Ph.D. 1998 - 2000 |
| RESEARCH UPDATED BY: Michael C. Tims, PhD. cand. June 2001 |
| REVISED BY: J Mohanasundaram, MD, PhD January 2007 |
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