Emodin prevents ethanol-induced developmental anomalies in cultured mouse fetus through multiple activities

Maternal alcohol ingestion on pregnant period causes fetal alcohol syndrome including psychological and behavioral problems, and developmental abnormality. In this study, we investigated the effect of emodin, an active anthraquinone component found in the roots and bark of the genus Rhamnus (Buckthorn), on ethanol-induced teratogenesis during embryonic organogenesis.

We cultured mouse embryos on embryonic day 8.5 for 2 days with ethanol (5 μl/3 ml) and/or emodin (1×10(-5) and 1×10(-4) μg/ml) using a whole embryo culture system and then investigated the developmental evaluation, superoxide dismutase (SOD) activity, and expression patterns of cytoplasmic SOD (SOD1), mitochondrial SOD (SOD2), cytosolic glutathione peroxidase (cGPx), tumor necrosis factor-α (TNF-α), caspase 3, and hypoxia inducible factor 1α (HIF-1α).

Morphological parameters, including growth in yolk sac and fetal head, body length, and development of the central nervous system, circulation system, sensory organs, skeletal system, and limbs in embryos exposed to ethanol were significantly decreased compared to those of the normal control group, but co-treatment with emodin (1 × 10(-5) and 1 × 10(-4) μg/ml) significantly improved these parameters. Furthermore, the reduced levels of SOD activity, and SOD1, SOD2, cGPx, and HIF-1α and the increased gene levels of TNF-α and caspase-3 due to ethanol exposure were significantly restored by cotreatment with emodin. Birth Defects Res (Part B) 98:268-275, 2013. © 2013 Wiley Periodicals, Inc.

This study revealed that cotreatment with emodin significantly prevented teratogenesis induced by ethanol, not only by modulating hypoxia and antioxidant enzymes, but also by attenuating the enhanced levels of TNF-α and caspase 3 in cultured embryos. Therefore, emodin may be an effective preventive agent for ethanol-induced teratogenesis.