Ginsenoside Saponin Rg1 can Prevent Ethanol-Induced Neurocranial Cartilage Deformities in a Fish Model of Fetal Alcohol Spectrum Disorder

Fetal Alcohol spectrum disorder (FASD) is an important clinical problem resulting from prenatal alcohol exposure. It can cause serious central nervous system (CNS), cardiovascular, and craniofacial defects. An effective method for the prevention of FASD, other than women abstaining from drinking alcohol during pregnancy, is not known. The synthetic drugs recommended for the treatment of alcoholism cannot be used by women during pregnancy which led us to investigate natural products as a potential source for new therapies. Many herbs including Asian ginseng (Panax ginseng) have therapeutic potencies on alcoholism. Recently, black ginseng (prepared from red ginseng) has been shown to inhibit ethanol-induced teratogenesis in mouse embryos in vitro [1]. We therefore tested the potency of Asian ginseng (PG) as an antialcoholic agent using medaka (Oryzias latipes) as an animal model. Previously we demonstrated that medaka embryos exposed to ethanol developed microcephaly with neurocranial cartilage deformities which were analogous to human FASD phenotypes. Moreover, chondrification in many cartilages, especially in ethmoid plate (EP), trabecular cartilages (TC), and polar cartilages were inhibited by ethanol. These inhibitions might be related to cleft palate development, a birth defect observed in a few cases of human FASD phenotypes. Further, we have observed that ethanolic extracts of PG root can prevent some of these neurocranial deformities induced by ethanol in medaka. PG consists of many ginsenosides including Re, Rg1, Rb1, Rc, Rb2 and Rg3 as saponins. At present we are evaluating the effects of individual ginsenosides to find the most effective and appropriate compound that can prevent the neurocranial cartilage deformities induced by ethanol in medaka. Preliminary data indicates that medaka embryos exposed to ethanol (300 mM) with 25µg/ml Rg1 is able to restore TC in the neurocranium. This study indicates that ginsinoside saponins are able to attenuate ethanol teratogenesis in medaka. Acknowledgements: Thanks go to the United States Department of Agriculture, Agriculture Research Service, Specific Cooperative Agreement No. 58–6408–2-0009. Reference:[1] Lee SR, Kim MR, et al. (2009) Toxicology in vitro, 23: 47–52.