Berberine Enhanced Antidiabetic Effects And Attenuated Untoward Effects Of Canagliflozin In Streptozotocin-induced Diabetic Mice

Diabetes Mellitus is a complex chronic disease mainly involved in glucose metabolism.It exhibits some common charactors,namely increased blood glucose,urine glucose,mpaired glucose tolerance,increased diet,and water intake,urine excretion.A relative or absolute deficiency of insulin secretion or insulin resistance resulted in those changes,which is widely recognized.This disease finally caused the other metabolic disorders,such as lipids,proteins,electrolytes,water and so on.Besides of these it also developed diabetic complications.According to the updated statistics,the number of patients with diabetes mellitus will rise to 592 million in 2035.The prevalence,mortality and danger have remained upward trends these years.And the patients are younger and younger around the world.Obvously,it has become a key killer of human beings,therefore,it's a necessity for developing an efficient and rational treatment.Although common antidiabetes drugs have function on lowering glucose,but long-term monotherapy became unsustainable in regulating blood glucose,even caused adverse aspects.It already existed combination ways of diabetes mellitus treatment in clinical trials,which point out the trend of enhanced antidiabetic effects and attenuated untoward effects by combination ways.Canagliflozin approved by FDA in 2013 is a novel antidiabetic drug,which belongs to the class of sodium-glucose transptor 2 inhibitor.This drug involves the inhibition of SGLT2 in kidneys,blocking the reabsorption of renal glucose,then the surplus glucose was excreted as urine.But the adverse aspects of increasing urine excretion,urinary tract infection,renal dysfunction.Berberine,a compound from traditional Chinese medicine,was confirmed the ability of regulating the metabolism of glucose and lipids,and also used as an antipyretic and anti-bacterial medicine.In the current study,we investigated the enhanced antidiabetic effects and attenuated untoward effects of Canagliflozin combinated with Berberine in streptozotocin-induced diabetic mice.We have evaluated the improvements of related indicators in diabetic mice,which mean a new idea for diabetes mellitus treatment.Diabetic NIH mice were orally administrated with Canagliflozin,Berberine,and Canagliflozin conbined with Berberine(BC)respectively.The diet,water intake,urine excretion,total urine glucose were monitored in those mice.We also tested the concentration of glucose,cholesterol,triglycerides,high density lipoprotein cholesterol,low density lipoprotein cholesterol,insulin,creatinine,and urea in serum;finally we detected the malondialdehyde concentration,superoxide dismutase activity and the expression of 5'-AMP-activated protein kinase and tumor necrosis factor a in kidneys.We have found the combination is prior to canagliflozin or berberine alone in several aspects,namely blood glucose homeostasis,the improvement of glucose tolerance,diet,water intake,urine excretion,total urine glucose and so on.In addition,we have discovered BC up-regulated the expression of 5' AMP-activated protein kinase,but down-regulated that of tumor necrosis factor a in kidney.In summary,we first showed BC enhanced antidiabetic effects and alleviaed renal adverse aspects.The antidiabetic effect is likely mediated by synergically promoting the expression of pAMPK and reducing the expression of TNF? in kidneys.Therefore,BC is probably to be a new combination for diabetes mellitus treatment,especially for those patients who can't tolerate insulin administration.But as for the exact mechanism of BC,it still requires further study.