Catalpol ameliorates advanced glycation end product-induced dysfunction of glomerular endothelial cells via regulating nitric oxide synthesis by inducible nitric oxide synthase and endothelial nitric oxide synthase

IUBMB Life. 2019 Sep;71(9):1268-1283. doi: 10.1002/iub.2032. Epub 2019 Mar 12.

Abstract

Catalpol (Cat.) is an iridoid glucoside extracted from the root of Rehmannia glutinosa Libosch. In this study, we investigated whether Cat. could protect the mouse glomerular endothelial cells against the deleterious effect induced by advanced glycation end products (AGEs) and explored potential mechanisms. We found that 10 μM Cat. showed a protective effect on dead cells stimulated by AGEs. Cat. significantly decreased the expression of p-NF-κBp65 and inducible nitric oxide synthase (iNOS) and increased the expression of phosphorylated-endothelial nitric oxide synthase (p-eNOS; Ser1177), PI3K, p-Akt (Thr308), and total-Akt. Moreover, Cat. restored the integrity of glomerular endothelial barrier by increasing endothelial tight gap junction protein and ameliorated the endothelial hyperpermeability induced by AGEs via modulating the nitric oxide (NO) production. Additionally, Cat. attenuated the massive release of NO induced by AGEs, inhibiting the macrophage infiltration by modulating the NO production, accompanied by the decrease in the release of monocyte chemoattractant protein-1 and intercellular cell adhesion molecule-1 in vitro. Therefore, Cat. ameliorated AGEs-induced endothelial dysfunction via inhibiting the NF-κB/iNOS pathway and activating the PI3K/Akt/eNOS pathway. © 2019 IUBMB Life, 71(9):1268-1283, 2019.

Keywords: advanced glycation end products; catalpol; endothelial dysfunction; nitric oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL2 / genetics*
  • Endothelial Cells / metabolism
  • Glycation End Products, Advanced / genetics
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics*
  • Iridoid Glucosides / pharmacology*
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / genetics
  • Kidney Diseases / pathology
  • Kidney Glomerulus / drug effects*
  • Kidney Glomerulus / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • NF-kappa B / genetics
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / genetics
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type III / genetics
  • Oncogene Protein v-akt / genetics
  • Phosphatidylinositol 3-Kinases / genetics

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Glycation End Products, Advanced
  • Icam1 protein, mouse
  • Iridoid Glucosides
  • NF-kappa B
  • Intercellular Adhesion Molecule-1
  • catalpol
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Oncogene Protein v-akt