Berberine enhanced antidiabetic effects and attenuated untoward effects of canagliflozin in streptozotocininduced diabetic mice

OBJECTIVE To determine whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus.METHODS Streptozotocin-induced diabetic mice were introduced,and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated.RESULTS Berberine combined with canagliflozin(BC)increased reduction of fasting and postprandial blood glucose,diet,and water intake compared with berberine or canagliflozin alone.Interestingly,BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone.In addition,BC showed increased phosphorylated 5′AMP-activated protein kinase(pA MPK)expression and decreased tumor necrosis factor alpha(TNFα)levels in kidneys compared with berberine or canagliflozin alone.CONCLUSION These results indicated that BC is as tronger antidiabetic than berberine or canagliflozin alone with less negative side effectson the kidneys of diabetic mice.The antidiabetic effect is likely mediated by synergically promoting the expression of p AMPK and reducing the expression of TNFαin kidneys.This study first proved that canagliflozin combined withberberine is apromising treatment for diabetes mellitus.However,the exact mechanisms should be further investigated in future studies.