The renoprotective effects of berberine via the EP4-Gαs-cAMP signaling pathway in different stages of diabetes in rats

Abstract

Aims: To investigate the renoprotective roles of berberine (BBR) in different stages of diabetic nephropathy (DN) in streptozotocin (STZ)-induced diabetic rats fed a high-sugar and high-fat diet. Methods: Diabetes was induced in mice by intraperitoneal injection of STZ, and the mice were then randomly divided into groups: normal, diabetes, high-sugar and high-fat and BBR (high, median and low dose) groups. The body weight (BW), kidney weight to body weight (KW/BW), blood urea nitrogen, urine total protein to urine creatinine ratio and serum creatinine were measured on different weeks throughout the study. The protein levels of E prostanoid receptor 4 (EP4), Gαs and content of cAMP in the kidney were, respectively, detected by western blot analysis and RIA analysis. Results: In the DN rats, there was remarkable renal damage. BBR restored renal functional parameters, suppressed alterations in histological and ultrastructural changes in the kidney tissues and increased EP4, Gαs and cAMP levels compared with those of the DN model group. In addition, BBR has different therapeutic effects during the different stages of the development of DN, and it works best in the sixth week. Conclusion: These studies demonstrate, for the first time, that BBR exerts renoprotective effects in different stages of DN via EP4- Gαs- AC-cAMP signaling pathway in STZ-induced DN rats fed a high-sugar and high-fat diet.