Blue Cohosh's Teratogenic Effect is Restricted to the Cardiovascular System in Medaka

Blue cohosh (Caulophyllum thalictroides) (BC) is a perennial herb used by the Native American Indian women to induce labor and to treat other uterine complications. The safety and effectiveness of this herbal product have not yet been evaluated by the Food and Drug Administration (FDA), however, several reports indicated that BC by some unknown mechanisms is able to induce teratogenic effects in new born babies [1,2]. To explore the mechanism we have used Japanese medaka (Oryzias latipes) embryo-larval development as the model and a methanolic extract of BC root as the teratogen. Fertilized medaka eggs at various stages of development were exposed to BC (0–20 ug/ml) either for 24 or 48 h and examined on 10 day post fertilization (dpf). The embryo mortality, hatching efficiency and morphological abnormalities in craniofacial, cardiovascular and skeletal organs were considered for the evaluation of the teratogenic potency of the herbal product. Embryos at late stages of development (Iwamatsu stage 32) were more sensitive to BC than the embryos at early stages (Iwamatsu stage 10). The calculated LC₅₀ is 6.96 µg/ml; however, BC was unable to induce any structural alteration with regard to craniofacial and skeletal systems in medaka. The cardiovascular system was found to be abnormal both structurally and functionally in the embryos treated with BC and this might be the major teratogenic effect. Acknowledgements: Partial support of this research from the National Center for Natural Product Research, School of Pharmacy, University of Mississippi, is gratefully acknowledged. References: [1] Woldemariam TZ, et al. (1997) J. Pharm. Biomed. Anal. 15: 839–843. [2] Kennelly EJ, et al. (1999) J. Nat. Prod. 62: 1385–1389.