Study of anti-diabetic nephropathy efficacy of berberine analogue Y53 in STZ-induced diabetic C57 BL/6 J mice / 中国药理学通报

ABSTRACT

Aim To investigate the ameliorative effects pseudoberberine(Y53), a berberine(BBR) analogue, on diabetic nephropathy( DN) in streptozotocin( STZ)-induced diabetic mice. Methods Diabetes mellitus ( DM) of the C57BL/6J mice was induced by intraper-itoneal injection of STZ at 120 mg·kg-1 . The diabetic animals were divided into 4 groups, which were orally treated with saline, 50 mg · kg-1 of BBR, 50 mg · kg-1 of Y53 or 5 mg · kg-1 of rosiglitazone ( ROSI ) , respectively. During and after the experiment, the u-rine, blood, serum and kidney of the animals were harvested for determination of relevant parameters by kits. Kidney tissues of the mice were subjected to pathological examination by hematoxylin & eosin( HE) staining;mRNA and protein expression levels of target genes in the kidney were determined by quantitative re-al-time reverse transcriptase-polymerase chain reaction ( qRT-PCR) and Western blot, respectively. Results Y53 greatly reduced the fasting blood glucose ( FBG ) and glycosylated hemoglobin( GHb) , improved diabet-ic symptoms such as polyphagia and polyuria in the di-abetic mice( P<0. 01 vs DM control group) . Y53 po-tently reduced the blood urea nitrogen ( BUN ) , serum creatinine( Scr) , 24 h urinary protein, kidney index, serum and kidney advanced glycation end-products ( AGEs) and nitric oxide( NO) , as well as kidney cho-lesterol( CHO ) and triglyceride ( TG ) contents ( P <0. 05 or P<0. 01 vs DM control group) . In the patho-logical examination, Y53 greatly restored kidney mor-phology and suppressed glomerular sclerosis( P<0. 001 vs DM control group). In addition, Y53 significantly reduced the renal expression of fibrosis-related genes, such as the transforming growth factor-β1 ( TGF-β1 ) and smad2(P<0. 01 vs DM control group). The reno-protective efficacies of Y53 were superior to those of BBR and ROSI in our study ( P<0. 05 or P<0. 01 ) . Conclusions The BBR analogue Y53 has potent ac-tivities in ameliorating renal injury and restoring renal function in STZ-induced diabetic mice. Y53 may be developed as a novel kind of agent for the treatment of DN in the future.