Evaluation of synthetic galloylated compounds on zebrafish immune response and development: Insights from toxicity and gene expression analyses.

Abstract

This study evaluated the developmental toxicity and immunomodulatory effects of three synthetic galloylated compounds, including 4-galloyloxy-DMC (4-G), 7-galloyloxychrysin (7-G), and 7-galloyloxypinocembrin (7-GP) using zebrafish (Danio rerio) embryos as a model. Embryos were exposed to each compound at concentrations of 10 nM, 100 nM, and 1 μM from 24 to 120 hours post-fertilization (hpf). Survival, hatching rates, morphological abnormalities, and immune-related gene expression (baxa, nfkb2, il6, and il8) were assessed. Among the compounds tested, 4-G exhibited significant toxicity at 1 μM, leading to increased malformations and reduced survival, prompting further testing at a lower concentration (100 nM). In contrast, both 7-G and 7-GP demonstrated no observable toxicity across all concentrations. Gene expression analysis revealed that 4-G significantly downregulated il8, suggesting immunosuppressive effects, while 7-GP significantly upregulated nfkb2, indicating potential immune activation via nfkb signaling. These findings demonstrate compound-specific effects of structurally similar galloylated molecules and underscore the importance of molecular configuration in modulating developmental toxicity and immune responses. The results support the further investigation of 7-GP as a safe and immunomodulatory compound for potential therapeutic applications.