Asian Ginseng (Panax ginseng) Potentiates Ethanol-Induced Cardiovascular Dysfunction in Medaka Embryogenesis (Oryzias latipes)
Alcohol is a teratogen, induces fetal alcohol spectrum disorder (FASD) which has serious central nervous system (CNS), cardiovascular, and craniofacial defects affecting the entire lifetime of an individual. 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 an investigation of natural products. Due to ethical constraints, FASD studies in humans are very limited and several animal models are used instead to understand the molecular mechanisms. We have observed that developmental ethanol exposure of medaka (Oryzias latipes) embryos generates features which are analogous to human FASD phenotypes . We hypothesize that ethanol metabolism generates oxidative stress which can disrupt embryonic development of medaka. In the present investigation, we have used root extracts of Asian ginseng (Panax ginseng) as a preventive agent of FASD. Fertilized medaka eggs within 4h post fertilization (hpf) were exposed to methanolic extracts (50 – 100 µg/mL) of ginseng root (PG) or ethanol (300 mM) either alone or in combination. After 48h of treatment the viable embryos were transferred to clean hatching solution and on 6 dpf the embryos were examined for vessel circulation followed by mRNA analyses of enzymes related to ethanol metabolism and oxidative stress. It was observed that ethanol (300 mM) alone was able to disrupt vessel circulation and co-treatment of PG (50 – 100 µg/mL) with ethanol enhanced the effect; PG (100 µg/mL) alone had no effect. mRNA analysis of alcohol metabolizing enzymes or oxidative stress-related enzymes did not show any significant alterations under any of these treatment conditions. It is therefore concluded that potentiation of ethanol-induced cardiovascular deformities in medaka by PG may be mediated through a different mechanism rather than oxidative stress. Acknowledgements: Thanks go to the United States Department of Agriculture, Agriculture Research Service, Specific Cooperative Agreement No. 1UO1FD004246. References:  Haron M, Powe D, et al. (2012) Adv Mol Tox, 6: 77 – 128.