Metabolite Profiling, Modulation of Glucose Metabolism and Antioxidant Activity Reveals the Protective Effect of Sulfated Polysaccharides From Gracilaria gracilis in Hepatic Tissues of Type 2 Diabetic Ra

ABSTRACT

Diabetic hepatopathy is one of the complications of Type 2 diabetes (T2D), and it's a major cause of mortality and morbidities associated with the disease. Seaweeds are good sources of bioactive compounds of medicinal importance and have shown potential as an alternative therapy for the treatment of diabetes. This study assessed the protective effect of sulfated polysaccharides (SPs) from a red seaweed specie ( Gracilaria gracilis ) against diabetic hepatopathy and its potential biochemical mechanisms in rats with T2D. SPs from G. gracilis (150 and 300 mg/kg bodyweight [bw]) were given orally to two groups of T2D rats, respectively. The diabetic and normal control groups were given water, while metformin served as the standard. Hepatic activities of glucose metabolic enzymes and oxidative stress parameters were assessed in the liver. Hepatic metabolites in liver tissues from the different groups were analyzed using chromatographic techniques. Induction of T2D led to significant decrease in glutathione level, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S‐transferase activities, while an increase in fructose‐1.6‐biphosphatase, glucose 6‐phosphatase and glycogen phosphorylase activities were observed in hepatic tissues. Glucose, lipid and amino acid metabolic pathways, and their metabolites were also dysregulated on induction of T2D. Treatment with SPs led to the reversal of the glutathione and malondialdehyde levels, as well as antioxidant enzyme activities, Furthermore a significant improvement in glucose, lipid, and amino acid metabolisms were observed in hepatic tissues of SPs treated diabetic rats. Our findings showed that SPs from G. gracilis exhibited protective effects against diabetic hepatopathy in T2D by attenuating lipotoxicity, oxidative stress, with concomitant improved glucose, lipid and amino acid metabolisms.