Protective role of ginger nanoparticles against hepatocellular carcinoma through regulation of DNA methylation and miRNA-34a-mediated apoptosis.

BACKGROUND

Hepatocellular carcinoma (HCC) is a common, aggressive, and potentially fatal malignancy. Ginger possesses a wide range of beneficial biological effects on different body organs. The present study investigated the therapeutic effects of ginger extract (GE) and ginger nanoparticles (GNPs) against HCC induced by diethylnitrosamine (DEN) and carbon tetrachloride (CCl₄).

METHODS

Treatment was initiated 15 weeks after HCC induction and continued for six consecutive weeks. Forty rats were equally divided into four groups. Group 1 (normal control): rats received saline; Group 2 (DEN/CCl₄): HCC-induced rats; Group 3 (HCC + GE): HCC-induced rats treated with ginger extract (300 mg/kg body weight/day); and Group 4 (HCC + GNPs): HCC-induced rats treated with ginger nanoparticles (50 mg/kg body weight/day). Liver function enzymes and gene expression levels were assessed in blood and tissue samples.

RESULTS

The HCC-induced group showed a significant elevation in liver marker enzymes, global DNA hypermethylation, upregulation of HAT1 and HDAC4, and downregulation of miRNA-34a expression. In contrast, treatment with GE or GNPs resulted in significant global DNA hypomethylation, downregulation of HAT1 and HDAC4, and upregulation of hepatic miRNA-34a expression.

CONCLUSION

The findings suggest that GE and GNPs suppress hepatocarcinogenesis, potentially through activation of the miRNA-34a pathway involved in apoptosis regulation.