Sanguinarine

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Sanguinarine
Sanguinarine Structure V.1.svg
Sanguinarine.png
Clinical data
ATC code
  • none
Identifiers
  • 13-Methyl-[1,3]benzodioxolo[5,6-c]-1,3-dioxolo[4,5-i]phenanthridinium
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.017.731 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C20H14NO4
Molar mass 332.335 g·mol−1
3D model (JSmol)
  • O1c3c(OC1)c2c[n+](c5c(c2cc3)ccc6cc4OCOc4cc56)C
  • InChI=1S/C20H14NO4/c1-21-8-15-12(4-5-16-20(15)25-10-22-16)13-3-2-11-6-17-18(24-9-23-17)7-14(11)19(13)21/h2-8H,9-10H2,1H3/q+1 Yes check.svgY
  • Key:INVGWHRKADIJHF-UHFFFAOYSA-N Yes check.svgY
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Sanguinarine is a polycyclic quaternary alkaloid. It is extracted from some plants, including the bloodroot plant, from whose scientific name, Sanguinaria canadensis, its name is derived; the Mexican prickly poppy ( Argemone mexicana ); [1] Chelidonium majus; and Macleaya cordata.

Contents

Toxicity

Sanguinarine is a toxin that kills animal cells through its action on the Na+/K+-ATPase transmembrane protein. [2] Epidemic dropsy is a disease that results from ingesting sanguinarine. [3]

If applied to the skin, sanguinarine may cause a massive scab of dead flesh where it killed the cells where it was applied, called an eschar . For this reason, sanguinarine is termed an escharotic. [4]

It is said to be 2.5 times more toxic than dihydrosanguinarine.

Alternative medicine

Native Americans once used sanguinarine in the form of bloodroot as a medical remedy, believing it had curative properties as an emetic, respiratory aid, and for a variety of ailments. [5] In Colonial America, sanguinarine from bloodroot was used as a wart remedy. Later, in 1869, William Cook's The Physiomedical Dispensatory included information on the preparation and uses of sanguinarine. [6] During the 1920s and 1930s, sanguinarine was the chief component of "Pinkard's Sanguinaria Compound," a drug sold by Dr. John Henry Pinkard. Pinkard advertised the compound as "a treatment, remedy, and cure for pneumonia, coughs, weak lungs, asthma, kidney, liver, bladder, or any stomach troubles, and effective as a great blood and nerve tonic." In 1931, several samples of the compound were seized by federal officials who determined Pinkard's claims to be fraudulent. Pinkard pleaded guilty in court and accepted a fine of $25.00. [7]

More recently, sanguinarine from bloodroot has been promoted by many alternative medicine companies as a treatment or cure for cancer; however, the U.S. Food and Drug Administration warns that products containing bloodroot, or other sanguinarine-based plants, have no proven anti-cancer effects, and that they should be avoided on those grounds. [8] Meanwhile, Australian Therapeutic Goods Administration also advise consumers not to purchase or use products marketed as containing Sanguinaria canadensis to cure or treat cancer, including certain types of skin cancer. [9] Indeed, oral use of such products has been associated with oral leukoplakia, a possible precursor of oral cancer. [10] In addition, the escharotic form of sanguinarine, applied to the skin for skin cancers, may leave cancerous cells alive in the skin while creating a significant scar. For this reason it is not recommended as a skin cancer treatment. [11] [12]

Biosynthesis

In plants, sanguinarine biosynthesis begins with 4-hydroxyphenyl-acetaldehyde and dopamine. These two compounds are combined to form norcoclaurine. Next, methyl groups are added to form N-methylcoclaurine. The enzyme CYP80B1 subsequently adds a hydroxyl group, forming 3'-hydroxy-N-methylcoclaurine. The addition of another methyl group transforms this compound into reticuline.

Notably, biosynthesis of sanguinarine up to this point is virtually identical to that of morphine. However, instead of being converted to codeinone (as in the biosynthesis of morphine), reticuline is converted to scoulerine via berberine bridge enzyme (BBE). As such, this is the commitment step in the sanguinarine pathway. [13] Although it is unknown exactly how scoulerine proceeds down the biosynthetic pathway, it is eventually converted to dihydrosanguinarine. The precursor to sanguinarine, dihydrosanguinarine is converted to the final toxin via the action of dihydrobenzophenanthridine oxidase. [14]

The biosynthesis of sanguinarine Chemistry of Poisons Project Pic.jpg
The biosynthesis of sanguinarine

See also

Related Research Articles

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<span class="mw-page-title-main">Papaveraceae</span> Family of flowering plants

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<span class="mw-page-title-main">Eschar</span> Piece of dead tissue caused by some skin injuries

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<span class="mw-page-title-main">Natural product</span> Chemical compound or substance produced by a living organism, found in nature

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<i>Sanguinaria</i> Genus of flowering plants in the poppy family Papaveraceae

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<i>Argemone mexicana</i> Species of plant

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In enzymology, a reticuline oxidase (EC 1.21.3.3) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Canadine</span> Chemical compound

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<span class="mw-page-title-main">Black salve</span> Ineffective and unsafe alternative medicine cancer treatment

Black salve, also known by the brand name Cansema, is an ineffective and unsafe alternative cancer treatment. The product is commonly classified as an escharotic—a topical paste which destroys skin tissue and leaves behind a scar called an eschar. Escharotics were widely used to treat skin lesions in the early 1900s, but have since been replaced by safer and more effective treatments. Escharotics, such as black salves, are currently advertised by some alternative medicine marketers as treatments for skin cancer, often with unsubstantiated testimonials and unsupported claims of effectiveness.

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<span class="mw-page-title-main">Cheilanthifoline</span> Chemical compound

(S)-Cheilanthifoline is a benzylisoquinoline alkaloid (BIA) which has been isolated from Corydalis dubia and Argemone mexicana. (S)-Cheilanthifoline is metabolically derived from (S)-reticuline, a pivotal intermediate in the biosynthesis of numerous BIAs. (S)-Cheilanthifoline is the immediate precursor of the BIA (S)-stylopine ((S)-stylopine synthase/CYP719A20), which is the precursor for the alkaloids protopine and sanguinarine.

Neoplasene is an herbal veterinary medicine derived from certain chemicals, such as sanguinarine, extracted from the perennial herb Sanguinaria canadensis. It is used to treat cancer in pet animals, especially dogs. Its effectiveness is unproven and there are serious adverse effects.

<span class="mw-page-title-main">BBE-like enzymes</span>

Berberine bridge enzyme-like form a subgroup of the superfamily of FAD-linked oxidases, structurally characterized by a typical fold observed initially for vanillyl-alcohol oxidase (VAO). This proteins are part of a multigene family (PF08031) that can be found in plants, fungi and bacteria.

References

  1. ↑ Santos AC, Adkilen P (1932). "The Alkaloids of Argemone Mexicana". Journal of the American Chemical Society. 54 (7): 2923–2924. doi:10.1021/ja01346a037.
  2. ↑ Pitts BJ, Meyerson LR (1981). "Inhibition of Na,K-ATPase Activity and Ouabain Binding by Sanguinarine". Drug Development Research. 1 (1): 43–49. doi:10.1002/ddr.430010105. S2CID   84619967.
  3. ↑ Das M, Khanna SK (May 1997). "Clinicoepidemiological, toxicological, and safety evaluation studies on argemone oil". Critical Reviews in Toxicology. 27 (3): 273–297. doi:10.3109/10408449709089896. PMID   9189656.
  4. ↑ Cienki JJ, Zaret L (October 2010). "An Internet misadventure: bloodroot salve toxicity". Journal of Alternative and Complementary Medicine. 16 (10): 1125–1127. doi:10.1089/acm.2010.0140. PMID   20932193.
  5. ↑ "Papaveraceae Sanguinaria canadensis L." BRIT - Native American Ethnobotany Database. Retrieved 2017-05-07– via herb.umd.umich.edu.
  6. ↑ "Sanguinaria Canadensis. Blood root, Red puccoon, Red turmeric". Henriette's Herbal Homepage. Retrieved 2017-05-07.
  7. ↑ "FDA Notices of Judgment Collection, 1908-1966". ceb.nlm.nih.gov. Retrieved 2017-05-07.
  8. ↑ "Do Not Use: Black Salve is Dangerous and Called by Many Names". FDA. Retrieved 2020-10-13.
  9. ↑ "Black and red salves in treating cancer". TGA. Retrieved 19 March 2012.
  10. ↑ Neville BW (2002-01-01). Oral & maxillofacial pathology. W.B. Saunders. ISBN   0721690033. OCLC   899021983.
  11. ↑ Sivyer GW, Rosendahl C (July 2014). "Application of black salve to a thin melanoma that subsequently progressed to metastatic melanoma: a case study". Dermatology Practical & Conceptual. 4 (3): 77–80. doi:10.5826/dpc.0403a16. PMC   4132006 . PMID   25126466.
  12. ↑ "Beware of black salve". American Academy of Dermatology. Retrieved 2018-07-02.
  13. 1 2 Alcantara J, Bird DA, Franceschi VR, Facchini PJ (May 2005). "Sanguinarine biosynthesis is associated with the endoplasmic reticulum in cultured opium poppy cells after elicitor treatment". Plant Physiology. 138 (1): 173–183. doi:10.1104/pp.105.059287. PMC   1104173 . PMID   15849302.
  14. ↑ "Chelirubine, Macarpine, and Sanguinarine Biosynthesis". Recommendations on Biochemical & Organic Nomenclature, Symbols & Terminology etc. International Union of Biochemistry and Molecular Biology.
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