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


CONCLUSIONS
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.
Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education , Hefei , China .
Yang
Y
Yang
Weijian
W
Ni
Ming
M
Cai
Liqin
L
Tang
Wei
W
Wei
D000818:Animals; D001599:Berberine / Q000008:administration & dosage*; D000242:Cyclic AMP / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin; D016896:Treatment Outcome
C545651:Ptger4 protein, mouse; D058309:Receptors, Prostaglandin E, EP4 Subtype; D001599:Berberine; D013311:Streptozocin; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs
Berberine; EP4; course of disease; diabetic nephropathy