title: Inhibition of phosphorylation of p38 MAPK involved in the protection of nephropathy by emodin in diabetic rats.
abstract: To explore the protection of emodin on renal dysfunction in the streptozotocin-induced diabetic rats with nephropathy and the role of p38 mitogen-activated protein kinase (p38 MAPK) signal transduction pathway in this protection. 30 male Spraque-Dawley rats were randomly divided into control group, model group and emodin group. The rats in the model group and emodin group were administered with streptozotocin (60 mg/kg) to induce diabetes. 40 mg/kg/day of emodin were orally given to the rats in emodin group. The rats in other groups were only given solvent. Biochemical index were analysed by oxidase and oxidase dynamical enzyme method. Glomerular area and volume were determined quantitatively by using Image Analysis System. Western blotting and immunohistochemical staining was used to detect the total p38 MAPK, phosphorylated p38 MAPK, phosphorylated cAMP response element binding protein (CREB) and fibronectin. The average kidney weight/body weight, glomerular area, glomerular volume and all biochemical indexes significantly increased in model group as compared to the control group (P<0.05), while the average body weight decreased. The expressions of phosphorylaed p38 MAPK, phosphorylated CREB and fibronectin increased by 1.98-fold, 1.94-fold and 1.96-fold respectively in model group compared with those in the control group (P<0.05). Emodin markedly decreased the average kidney weight/body weight, glomerular area, glomerular volume and all biochemical indexes (P<0.05), having a weak action on the level of blood glucose. The expressions of phosphorylated p38 MAPK, phosphorylated CREB and fibronectin also significantly downregulated in emodin group compared with those in model group (P<0.05). Emodin was efficient to ameliorate renal dysfunction in diabetic nephropathy rats probably by its inhibition of the activation of p38 MAPK pathway and downregulation of the expression of fibronectin.
authors.affiliation: Lab of Pharmacology and Toxicology, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Wang
authors.forename: Heqing
authors.initials: H
authors.lastname: Huang
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
authors.forename: Futian
authors.initials: F
authors.lastname: Tang
authors.forename: Jia
authors.initials: J
authors.lastname: Qin
authors.forename: Wenge
authors.initials: W
authors.lastname: Huang
authors.forename: Fengying
authors.initials: F
authors.lastname: Chen
authors.forename: Fenfen
authors.initials: F
authors.lastname: Guo
authors.forename: Weihua
authors.initials: W
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000503:physiopathology / Q000517:prevention & control*; D004642:Emodin / Q000494:pharmacology* / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000199:Actins; D001786:Blood Glucose; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D005353:Fibronectins; D048051:p38 Mitogen-Activated Protein Kinases; D004642:Emodin