Investigating the Effects of Gossypetin on Liver Health in Diet-Induced Pre-Diabetic Male Sprague Dawley Rats

The rising prevalence of non-alcoholic fatty liver disease among patients with type 2 diabetes mellitus has emerged as a global health challenge. Gossypetin (GTIN) is a natural flavonoid which has recently demonstrated antihyperglycaemic, antioxidant, and anti-inflammatory effects. Despite these findings, no studies have investigated its effects on liver health in the pre-diabetic state. Hence, this study aimed to investigate the effects of GTIN on liver health in diet-induced pre-diabetic male rats in the presence and absence of dietary intervention and to compare these effects with those of metformin (MET). Following 20 weeks of pre-diabetes induction, the animals were divided into six groups (<i>n</i> = 6) as follows: non-pre-diabetic (NPD) control, pre-diabetic (PD) control, and PD groups treated with GTIN (15 mg/kg body weight (bw)) or metformin (500 mg/kg bw) on either a normal diet or a high-fat, high-carbohydrate diet for 12 weeks. The results showed that the PD group had significantly higher liver triglycerides (TAG), liver weights, sterol regulatory binding element regulatory protein-1c (SREBP-1c), malondialdehyde (MDA) levels, and liver injury enzyme levels, along with decreased liver superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, and plasma bilirubin levels in comparison to NPD. Histologically, there was an increased lipid droplet accumulation and structural disarray in the PD group. GTIN treatment significantly reduced liver TAGs, liver weights, and plasma SREBP-1c levels, as well as improved liver SOD and GPx activity while decreasing liver MDA levels and liver injury enzymes in comparison to the PD control. Notably, GTIN treatment increased plasma bilirubin levels. Liver histology in the GTIN-treated groups revealed decreased lipid droplet accumulation and improved tissue integrity. Similar results were observed for the liver parameters in the MET-treated groups. The findings of this study may suggest that GTIN and MET exhibit therapeutic effects on liver health in diet-induced pre-diabetes in both the presence and absence of diet intervention. Dietary intervention may confer beneficial effects on liver health, with the most favorable therapeutic outcomes observed through a combination of treatment with dietary intervention. Additionally, GTIN may exhibit greater hepatoprotective effects than MET in rats without dietary intervention.