Evaluation of Panax ginseng ginsenosides as potential therapeutic agent of fetal alcohol spectrum disorders targeting CB1 receptors

Abstract

Identification of endocannabinoid receptor 1 subtype a (cnr1a) as a potential target of alcohol in Japanese medaka embryogenesis prompted us to use this model in discovering anti-alcoholic drugs from the natural products that may attenuate fetal alcohol spectrum disorder (FASD), a birth defect observed in the babies of mothers who ingested alcohol during pregnancy. FASD phenotypes are identified by growth retardation with central nervous system (CNS) malformation and dysfunction, and distinctive patterns of craniofacial, cardiovascular, and limb defects. The molecular mechanism(s) by which ethanol perturbs fetal development is unknown. Also, prevention of FASD, other than women abstaining from drinking alcohol during pregnancy, is not known. We have demonstrated that developmental exposure of fertilized medaka eggs to ethanol has generated several phenotypic end points in the neurocranium and cadriovasculature which are analogous to human FASD phenotypes. Moreover, the expression of cnr1a gene is reduced by developmental ethanol exposure. Further we have shown that ginseng root extract is able to partially rescue the embryos from the ethanol-induced developmental disorders. We will evaluate whether ginsenoside extracted from Panax ginseng is able to attenuate FASD in medaka embryos.