Blue Cohosh

Scientific Name(s): Caulophyllum thalictroides (L.) Michx. Family Berberidaceae (barberries)

Common Name(s): Blue cohosh , squaw root , papoose root , blue ginseng , yellow ginseng

Uses

Blue cohosh has been used to induce uterine contractions. It is widely advertised on the internet but is dangerous (see Toxicology and Adverse Reactions).

Dosing

Blue cohosh has traditionally been used at doses of 0.5 to 3 g/day; however, its potential for teratogenicity makes it unsuitable for women who are or may become pregnant. Because its principal indications are for gynecological disorders, avoid its use.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Documented adverse effects (including GI symptoms, contraction of uterine muscle, arterial constriction, inhibition of embryo implantation, and abortifacient effects). Avoid use.

Interactions

None well documented.

Adverse Reactions

Because blue cohosh can be toxic to humans and fetuses, there is little or no information about adverse reactions. Its toxicity appears to outweigh any medical benefit.

Toxicology

Blue cohosh root is potentially toxic to humans and fetuses.

Botany

Blue cohosh is an early spring perennial herb whose yellowish-green flowers mature into bitter, bright blue seeds. It is found throughout woodlands of the eastern and midwestern United States, especially in the Allegheny Mountains. The matted, knotty rootstock, collected in the autumn, is used for medicinal purposes. The root of an Asian species, C. robustum Maxim., has also been used medicinally.

History

Blue cohosh was used by Native Americans; the name “cohosh” comes from the Algonquin name of the plant. It was used by Menomini, Meskawi, Ojibwe, and Potawatomi tribes for menstrual cramps, to suppress profuse menstruation, and to induce contractions in labor. 1 It was widely used in 19th century Eclectic medicine as an emmenagogue, parturient, and antispasmodic. It continues to be used for regulating the menstrual cycle and for inducing uterine contractions.

Chemistry

The quinolizidine alkaloids anagyrine, baptifoline, and N-methylcytisine were isolated from blue cohosh rhizomes. 2 Other lupine alkaloids have been detected. 3 In addition to the quinolizidines, the aporphine alkaloid magnoflorine is found in substantial quantities. 2 Levels of the major quinolizidine alkaloids in herbal preparations have been determined by gas chromatography. 4 Blue cohosh root also contains triterpene saponins derived from hederagenin; 5 however, these saponins have not been purified or elucidated by modern chemical techniques. The saponins of the related species C. robustum have recently been more thoroughly characterized as a series of hederagenin bisdesmosides. 6

Uses and Pharmacology

Uterine stimulant

N-methylcytisine (caulophylline) was found to be a nicotinic agonist in animals 7 and to displace [ 3 H]nicotine from nicotinic acetylcholine receptors with 50 nm potency. 8 It was essentially inactive at muscarinic receptors. Other quinolizidine alkaloids were considerably less potent nicotinic ligands, with anagyrine having IC50 values greater than 100 mcm in these test systems. 8

Animal data

Magnoflorine has its own pharmacological properties, decreasing arterial blood pressure in rabbits and inducing hypothermia in mice, as well as inducing contractions in the isolated pregnant rat uterus and stimulating isolated guinea pig ileal preparations in cell membranes. 9 The blue cohosh saponins have uterine stimulant effects, as well as cardiotoxicity presumably due to vasoconstriction of coronary blood vessels. 10 Extracts of Caulophyllum given to rats were found to inhibit ovulation and affect the uterus. 11 The saponins of the Siberian species C. robustum (caulosides) have antimicrobial activity. 12 A mechanism for cytotoxicity has been suggested for cauloside C involving formation of pH-dependent channels. 13

Clinical data

Research reveals no clinical data regarding the use of blue cohosh as a uterine stimulant, as it can be toxic in humans and fetuses.

Dosage

Blue cohosh has traditionally been used at doses of 0.5 to 3 g/day; however, its potential for teratogenicity makes it unsuitable for women who are or may become pregnant. Because its principal indications are for gynecological disorders, avoid its use. 14

Pregnancy/Lactation

Documented adverse effects (including GI symptoms, contraction of uterine muscle, arterial constriction, inhibition of embryo implantation, and abortifacient effects). 15 , 16 Avoid use.

Interactions

None well documented.

Adverse Reactions

Blue cohosh can be toxic to humans and fetuses. Thus research reveals little or no information regarding adverse reactions associated with blue cohosh.

Toxicology

Blue cohosh berries are poisonous to children when consumed raw although the roasted seeds have been used as a coffee substitute. The root can cause contact dermatitis. 17 The alkaloid anagyrine is a teratogen in ruminants, 18 causing “crooked calf syndrome.” Another quinolizidine alkaloid in the plant, N-methylcytisine, was teratogenic in a rat embryo culture. 3 The skeletal malformations seen in calves have been postulated to be due to the action of the quinolizidine alkaloids on muscarinic and nicotinic receptors of the fetus, preventing normal fetal movements required for proper skeletal development.

A case was reported in which a newborn human infant, whose mother was administered blue cohosh to promote uterine contractions, was diagnosed with acute MI associated with CHF and shock. The infant eventually recovered after being critically ill for several weeks. 19 The FDA Special Nutritionals Adverse Event Monitoring System notes fetal toxicity cases of stroke and aplastic anemia following ingestion by the mother.

Bibliography

1. Erichsen-Brown C. Medicinal and other uses of North American plants. A historical survey with special reference to the Eastern Indian tribes . NY: Dover Press, 1980;355.
2. Flom M, et al. Isolation and characterization of alkaloids from Caulophyllum thalictroides . J Pharm Sci . 1967;56:1515-17.
3. Kennelly E, et al. Detecting potential teratogenic alkaloids from blue cohosh rhizomes using an in vitro rat embryo culture. J Nat Prod . 1999;62:1385-89.
4. Betz J, et al. Gas chromatographic determination of toxic quinolizidine alkaloids in blue cohosh Caulophyllum thalictroides (L.) Michx. Phytochem Anal . 1998;9:232.
5. McShefferty J, et al. Caulospogenin and its identity with hederagenin. J Chem Soc . 1956;449:2314.
6. Strigina L, et al. Cauloside A, a new triterpenoid glycoside from Caulophyllum robustum Maxim.: Identification of cauloside A. Phytochem . 1975;14:1583.
7. Scott C, et al. The pharmacological action of N-methylcytisine. J Pharmacol Exp Ther . 1943;79:334.
8. Schmeller T, et al. Binding of quinolizidine alkaloids to nicotinic and muscarinic acetylcholine receptors. J Nat Prod . 1994;57:1316-19.
9. El-Tahir K. Pharmacological actions of magnoflorine and aristolochic acid-1 isolated from the seeds of Aristolochia bracteata . Int J Pharmacognosy . 1991;29:101.
10. Ferguson H, et al. A pharmacologic study of a crystalline glycoside of Caulophyllum thalictroides . J Am Pharm Assoc (Sci Ed) . 1954;43:16.
11. Chandrasekhar K, et al. Proceedings: Observation on the effect of low and high doses of Caulophyllum on the ovaries and the consequential changes in the uterus and thyroid in rats. J Reprod Fertil . 1974;38:236-37.
12. Anisimov M. [The antimicrobial activity of the triterpene glycosides of Caulophyllum robustum Maxim.] Antibiotiki . 1972;17:834-37. Russian.
13. Likhatskaya G, et al. The pH-dependent channels formed by cauloside C. Adv Exp Med Biol . 1996;404:239-49.
14. Claus E, ed. Pharmacognosy . 3rd ed. Philadelphia, PA: Lea & Febiger; 1956.
15. Brinker FJ. Herb Contraindications and Drug Interactions . 2nd ed. Sandy, OR: Eclectic Medical Publications; 1998.
16. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG . 2002;109:227-235.
17. Hardin J, et al. Human poisoning from native and cultivated plants . Durham, NC: Duke University Press,1974;60.
18. Keeler R. Lupin alkaloids from teratogenic and nonteratogenic lupins. III. Identification of anagyrine as the probable teratogen by feeding trials. J Toxicol Environ Health . 1976;1:887-98.
19. Jones T, et al. Profound neonatal congestive heart failure caused by maternal consumption of blue cohosh herbal medication. J Pediatr . 1998;132:550-52.

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