Hepatoprotective effect of gallic acid against type 2-induced diabetic liver injury in male rats through modulation of fetuin-A and GLP-1 with involvement of ERK1/2/NF-κB and Wnt1/β-catenin signaling pathways

Gallic acid is a phenolic compound with biological and pharmacological activities. Therefore, our study aimed to examine whether gallic acid has a beneficial effect against type 2-induced diabetic hepatic injury in rats and attempt to discover its possible intracellular pathways. Adult male rats were subdivided into six groups: Control, DM (diabetes mellitus), GA (gallic acid)+DM, DM+GA, DM+MET (metformin) and DM+GA+MET. Type 2 diabetes mellitus (T2DM) induced a significant increase in the blood glucose, HOMA-IR, liver enzymes, fetuin-A, hepatic triglycerides content with diminished serum insulin and hepatic glycogen content associated with impairment of cellular redox balance. Administration of gallic acid successfully restored all these alterations which was confirmed by marked improvement of the histopathological changes of the liver. Significantly, gallic acid increased the expression of glucagon-like peptide-1 (GLP-1) immunoreactive cells in the terminal ileum with negative correlation observed between fetuin- A and GLP-1 cells. Furthermore, our results discovered that gallic acid could diminish the DM-induced hepatic damage via upregulated hepatic mRNA expression of GLUT-4, Wnt1 and beta-catenin with inhibitory effects on the elevated expression of ERK1/2/NF-kappa B. In conclusion, this study suggests that gallic acid provides a significant protection against T2DM-mediated liver injury. The use of gallic acid with traditional anti-diabetic drug enhanced its efficiency compared with traditional drug alone.

Automated summary

The study showed that gallic acid could effectively alleviate liver injury induced by type 2 diabetes, restore cellular balance, and improve blood glucose and liver function markers. Gallic acid increased the expression of GLP-1 and reduced diabetes-induced hepatic damage through various pathways.