Optimised <i>Gynura divaricata</i> polysaccharide extract ameliorated type 2 diabetes in mice by activating the PI3K/Akt/GLUT-4 signalling pathway

Type 2 diabetes mellitus (T2DM) is a long-term metabolic disorder, which is characterised by insulin resistance and persistent hyperglycaemia. Natural polysaccharides exhibit promising hypoglycaemic potential; however, optimising their extraction and mechanistic understanding of polysaccharides from Gynura divaricata (GDP) remain limited. Here, GDP underwent hot-water extraction followed by ethanol precipitation. A response surface methodology known as Box-Behnken design was utilised to refine the extraction process (extraction time, 120 min; temperature, 90 °C; solid-to-liquid ratio, 1:20 [g/mL]). Under these optimal conditions, the polysaccharide yield was 0.42% ± 0.03%. A homogeneous polysaccharide, GDP1, isolated and purified from GDP, exhibited potent hypoglycaemic activity in T2DM mice. GDP1 effectively decreased fasting blood glucose levels, ameliorated dyslipidemia, reduced inflammation and oxidative stress, and enhanced insulin sensitivity. GDP1 upregulated the levels of phosphorylated phosphoinositide 3-kinase (PI3K), Akt, and glucose transporter 4 (GLUT4), suggesting that its hypoglycaemic effect was partly owing to the activation of the PI3K/AkT/GLUT4 axis.