Coreopsis tinctoria buds polysaccharides boost metformin's antihyperglycemic effect in diabetic mice via gut microbiota and metabolism modulation

Coreopsis tinctoria bud is a characteristic plant of Xinjiang Uygur Autonomous Region, and it has various biological activities.This study investigated the effects of low-dose metformin (LMET) and the sodium hydroxide extract of Coreopsis tinctoria buds polysaccharides (Al) on streptozotocin-induced diabetes. The aim was to explore the potential mechanisms of LMET+Al and metformin alone in treating diabetes. The results showed that both metformin and LMET+Al could reduce weight loss and improve hyperglycemia in mice. Specifically, LMET+Al effectively lowered fasting blood glucose, enhanced glucose tolerance, promoted glycogen synthesis, improved islet function, and stimulated insulin secretion. It also better prevented islet cell atrophy by inhibiting cleaved Caspase-3 and the inflammatory factor NLRP-3. Gut microbiota analysis revealed higher levels of the probiotic Ligilactobacillus in the LMET+Al group compared to the metformin group. Metabolite analysis indicated that LMET+Al regulated diabetic mice through pathways like Aspartate Metabolism and Sphingolipid Metabolism. Correlation analysis showed that gut microbiota and metabolites were closely linked, with sphingosine positively correlated with Muribaculum and Alistipes_A ( p < 0.05) and negatively correlated with Acinetobacter ( p < 0.05). These interactions collectively contributed to host health. The findings suggest that Al may serve as a useful adjunct hypoglycemic agent for metformin in future applications. • The hypoglycemic effect of the combined application of Lose-dose Al and metformin is better than that of metformin alone. • Lose-dose Al and metformin protectd pancreatic tissue by reducing damage and suppressing cleaved Caspase-3/NLRP-3 expression. • Lose-dose Al and metformin modulatedgut microbiota, notably increasing beneficial Ligilactobacillus abundance. • Lose-dose Al and metformin improved metabolic disorders and demonstrates potential as a natural anti-diabetic agent.