title: Berberine ameliorates renal injury by regulating G proteins-AC- cAMP signaling in diabetic rats with nephropathy.
abstract: Diabetic nephropathy (DN) is a progressive kidney disease that is caused by injury to glomerulus and glomerular mesangial cells (MCs) proliferation play a critical role in the pathogenesis of DN. The current studies were undertaken to investigate the protective effects and the possible molecular mechanism of berberine on streptozotocin (STZ)-induced DN rats. Male Wistar rats were randomly assigned to normal control and DN groups of comparable age. Three DN groups received 50, 100 and 200 mg/kg of berberine for 8 weeks via daily intragastrically, respectively. The G proteins-adenylyl cyclase (AC)-cAMP signaling pathway and glomerular MCs proliferation were examined in STZ-induced diabetic rat kidney. Enhanced MCs proliferation and remarkable renal injury were concomitant with activation of Gαi and inhibition of Gαs and cAMP in DN model group. Berberine treatment for 8 weeks abolished the above changes by upregulating the expression of Gαs protein and downregulating the expression of Gαi protein, increasing cAMP level, and inhibiting MCs proliferation compared with model group. Taken together, for the first time, these results demonstrated that berberine can relieve renal injury in DN rats through mediating G proteins-AC-cAMP signaling pathway and inhibiting the abnormal proliferation of MCs by increasing cAMP level, suggesting that berberine could be a potential therapeutic agent for the treatment of DN.
authors.affiliation: Department of Pharmacy, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, Anhui, People's Republic of China. tulcyl@vip.sina.com
authors.forename: Li Qin
authors.initials: LQ
authors.lastname: Tang
authors.forename: Feng Ling
authors.initials: FL
authors.lastname: Wang
authors.forename: Ling Na
authors.initials: LN
authors.lastname: Zhu
authors.forename: Fei
authors.initials: F
authors.lastname: Lv
authors.forename: Sheng
authors.initials: S
authors.lastname: Liu
authors.forename: Shan Tang
authors.initials: ST
authors.lastname: Zhang
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001599:Berberine / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D024141:Collagen Type IV / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005215:Fasting / Q000097:blood; D005353:Fibronectins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; C526316:CCN2 protein, rat; D024141:Collagen Type IV; D005353:Fibronectins; D053773:Transforming Growth Factor beta1; D001599:Berberine; D055513:Connective Tissue Growth Factor; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases