Anti-diabetic effect of Ornithogalum caudatum Jacq. polysaccharides via the PI3K/Akt/GSK-3β signaling pathway and regulation of gut microbiota

Abstract

This study evaluated the anti-diabetic effect of polysaccharides isolated from Ornithogalum caudatum and their underlying mechanisms. To achieve this, a type 2 diabetes mellitus mouse model was established using a combination of a high-fat diet and low-dose streptozotocin injection. The mice were treated with Ornithogalumcaudatum polysaccharides (OCPs) for 4 weeks. OCPs treatment significantly decreased body weight loss, fasting blood glucose levels, and plasma insulin levels in diabetic mice. Additionally, compared with the untreated group, OCPs treatment significantly decreased total cholesterol, triacylglycerol, and low-density lipoprotein-cholesterol levels, but increased those of high-density lipoprotein-cholesterol in diabetic mice. Moreover, antioxidant enzyme activity and histopathology results revealed that OCPs effectively alleviated oxidative stress and streptozotocin-induced lesions by increasing antioxidant enzyme activity. Results from mechanistic studies showed that OCPs treatment significantly increased the expression of p-PI3K, p-Akt, and p-GSK-3β in the liver. Moreover, OCPs optimized the gut microbiota composition of diabetic mice by significantly decreasing the Firmicutes/Bacteroidetes ratio and increasing the levels of beneficial bacteria (Muribaculaceae_norank, Prevotellaceae_UCG-001 and Alloprevotella). Overall, these findings suggest that OCPs exert anti-diabetic effects by triggering the PI3K/Akt/GSK-3β signaling pathway and regulating the gut microbiota.