Renoprotective effects of berberine and its potential effect on the expression of β-arrestins and intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in streptozocin-diabetic nephropathy rats

J Diabetes. 2016 Sep;8(5):693-700. doi: 10.1111/1753-0407.12349. Epub 2015 Dec 29.

Abstract

Background: Berberine has been shown to exert protective effects against diabetic nephropathy (DN), but the mechanisms involved have not been fully characterized. The aim of the present study was to explore the effects of berberine on the expression of β-arrestins, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in DN rat kidneys and investigate the underlying molecular mechanisms.

Methods: To create the DN model, rats fed a high-fat and high-glucose diet were injected with a single dose of streptozotocin (35 mg/kg, i.p.). Then, DN rats were either treated or not with berberine (50, 100, 200 mg/kg per day, i.g., 8 weeks). Periodic acid-Schiff staining was used to evaluate renal histopathological changes. Renal tissue levels of β-arrestin 1 and β-arrestin 2 were determined by Western blot analysis, whereas immunohistochemistry was used to determine renal ICAM-1 and VCAM-1 levels.

Results: Berberine (100, 200 mg/kg) ameliorated the histopathological changes in the diabetic kidney. Western blot analysis revealed significant increases in ICAM-1 and VCAM-1 levels in the kidneys of DN rats, which were reversed by treatment with 100 and 200 mg/kg berberine. In addition, berberine treatment (50, 100, 200 mg/kg) increased diabetic-induced decreases in β-arrestin 1 and β-arrestin 2.

Conclusions: Berberine exhibited renoprotective effects in DN rats. The underlying molecular mechanisms may be associated with changes in the levels and regulation of β-arrestin expression, as well as ICAM-1 and VCAM-1 levels in the rat kidney.

Keywords: berberine; diabetic nephropathy; intercellular adhesion molecule-1 vascular cell adhesion molecule-1 β-arrestin; β-arrestin; 小檗碱; 糖尿病肾病; 细胞间粘附分子; 血管细胞粘附分子.

MeSH terms

  • Animals
  • Berberine / pharmacology*
  • Blotting, Western
  • Diabetes Mellitus, Experimental / complications*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / prevention & control*
  • Dose-Response Relationship, Drug
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Phytotherapy
  • Protective Agents / pharmacology
  • Rats, Sprague-Dawley
  • Vascular Cell Adhesion Molecule-1 / metabolism*
  • beta-Arrestins / metabolism*

Substances

  • Protective Agents
  • Vascular Cell Adhesion Molecule-1
  • beta-Arrestins
  • Berberine
  • Intercellular Adhesion Molecule-1