title: Renoprotective effects of berberine and its possible molecular mechanisms in combination of high-fat diet and low-dose streptozotocin-induced diabetic rats.
abstract: Berberine (BBR), an effective compound of Chinese traditional herbal medicine, has preventive effects on diabetes and its complications. In this study, we investigated the therapeutic effects and underlying molecular mechanisms of BBR in rats with high-fat diet and streptozotocin (STZ)-induced diabetic nephropathy model. BBR (50, 100, 200 mg/kg/d) were orally administered to male Sprague-Dawley rats after STZ injection and conducted for 8 weeks. Renal damage was evaluated by kidney weight to body weight ratio (KW/BW), urine microalbumin (UMAlb), urine protein for 24 h (UP24 h), urine creatinine (UCr), and histological examination. Type IV collagen and transforming growth factor-beta1 (TGF-β1) were detected by immunohistochemistry and ultrastructure of glomeruli was observed. Fasting blood glucose (FBG),serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c) in serum and G protein-coupled receptor kinases (GRKs), cAMP in kidney were measured. Remarkable renal damage, hyperglycemia and hyperlipidemia were observed in DN rats. BBR could restore renal functional parameters, suppress alterations in histological and ultrastructural changes in the kidney tissues, improve glucose and lipid metabolism disorders, and increase cAMP levels compared with those of DN model group. Furthermore, BBR down-regulated total protein expression of GRK2, GRK3 and up-regulated expression of GRK6 of renal cortex in DN rats, but had a slight effects on GRK4 and GRK5. These studies demonstrate, for the first time, that BBR exerts renoprotection in high-fat diet and STZ-induced DN rats by modulating the proteins expression of GRKs in G protein- AC-cAMP signaling pathway.
authors.affiliation: Department of Pharmacy, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, Anhui, People's Republic of China.
authors.forename: Feng Ling
authors.initials: FL
authors.lastname: Wang
authors.forename: Li Qin
authors.initials: LQ
authors.lastname: Tang
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.forename: Ling Na
authors.initials: LN
authors.lastname: Zhu
authors.forename: Ming
authors.initials: M
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D001599:Berberine / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000209:etiology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005215:Fasting / Q000097:blood; D054768:G-Protein-Coupled Receptor Kinases / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D009929:Organ Size; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013311:Streptozocin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D020011:Protective Agents; D001599:Berberine; D013311:Streptozocin; D000242:Cyclic AMP; D054768:G-Protein-Coupled Receptor Kinases