US EPA

1168300 

Journal Article 

Screening of the dietary supplement blue cohosh for potentially teratogenic alkaloids using rat embryo culture 

Flynn, TJ; Kennelly, EJ; Mazzola, EP; Mccloud, TG; Betz, JM 

1998 

1 

Teratology
ISSN: 0040-3709
EISSN: 1096-9926 

DART/TER/98000985 

May 

4/5 

219 

English 

BCI:BCI199800385072 

The roots of blue cohosh (Caulophyllum thalictroides) have been used in traditional medicine by Native American women to induce labor. Currently, this plant can be purchased in many health food stores as a dietary supplement, and it is promoted for use in female reproductive health as well as a variety of other conditions such as anxiety and asthma. Previous studies have identified some of the alkaloids and saponins from this plant. In this study, the powdered roots of blue cohosh were extracted with methanol. The methanol extract was then partitioned with ethyl acetate and n-butanol. The methanol, ethyl acetate, and n-butanol fractions were each tested in the rat embryo culture system. The ethyl acetate extract displayed toxicity and was further purified to yield two novel alkaloids: thalictroidine and caulophyllumine. The alkaloids magnoflorine, anagyrine, baptifoline, alpha-isolupanine and N-methylcytisine were also identified. Preliminary experiments with purified compounds indicate that caulophyllumine is extremely embryotoxic (100% lethality at 5 ug/mL) and that N-methylcytisine may be potentially teratogenic (neural tube defects were observed at a concentration, 80 ug/mL, that was only minimally growth inhibitory). The other compounds tested induced abnormalities only at concentrations that also severely retarded overall growth and development. Work is continuing on further characterization of the embryotoxicity of caulophyllumine and N-methylcytisine as well as the isolation and embryotoxicity screening of other alkaloidal components.