Gender associated effects of the ethanolic extracts of Chinese propolis on the hepatic transcriptome in ethanol-treated mice

The current study investigated the potential hepatoprotective effects of the ethanolic extracts of Chinese propolis (EECP) on ethanol-induced fatty liver in mice. C57BL/6J mice were orally gavaged with 50% ethanol alone or co-administrated with EECP at the dose of 0.2 ml/kg bodyweight for eight weeks. The dose for ethanol was 6 ml/kg bodyweight for the first two experimental weeks, and then increased to 8, 10, and 12 ml/kg bodyweight every two experimental weeks. Alterations in the hepatic transcriptome due to concomitant administration of EECP were investigated using RNA-Seq technique. Our results showed that the main EECP-responsive genes were involved in lipid syntheses, which were significantly down-regulated in both female and male mice co-administrated with EECP. In female mice, these differentially expressed genes (DEGs) were mainly associated with fatty acid biosynthesis. While in male mice, these DEGs were mainly involved in the steroid metabolic process and cholesterol biosynthetic process. Despite the sex-associated responses in lipid metabolism, EECP also exerted other beneficial effects in female mice through modulation of the cytokine-cytokine receptor interaction pathway that helped explaining its hepato-protective effectiveness. Our findings indicated that the mechanism regarding the hepato-protective effects of EECP was gender-dependent, which is worthy of further investigation during the development of therapeutic interventions using EECP to reduce the adverse influences of ethanol.