Astragaloside IV attenuates Toll-like receptor 4 expression via NF-κB pathway under high glucose condition in mesenchymal stem cells

Eur J Pharmacol. 2012 Dec 5;696(1-3):203-9. doi: 10.1016/j.ejphar.2012.09.033. Epub 2012 Oct 3.

Abstract

Diabetic hyperglycemia causes a variety of pathological changes. Astragaloside IV (AS-IV) was widely used for the treatment of cardiovascular diseases in China. The aim of this study was to determine the effect of AS-IV on bone marrow mesenchymal stem cells (MSCs) and the underlying mechanism in diabetes. We used reverse transcription polymerase chain reaction and western blotting to determine the expression of Toll-like receptor 4 (TLR4), matrix metalloproteinase-2 (MMP-2) and NF-κB p65 in MSCs under high glucose (HG) with or without pretreatment with AS-IV. The surface expression of TLR4 was checked by flow cytometry and the expression of TNF-α and MCP-1 were detected by ELISA in diabetes patients treated with AS-IV. AS-IV promoted the proliferation of MSCs and attenuated the increased expression of TLR4 induced by HG. In addition, AS-IV decreased the HG-induced translocation of NF-κB p65 and increased the MMP-2 expression in MSCs. AS-IV decreased the TLR4, TNF-α and MCP-1 expression in patients. Collectively,our data revealed that AS-IV attenuated TLR4 expression through the NF-κB signaling pathway in MSCs.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chemokine CCL2 / blood
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / metabolism
  • Drugs, Chinese Herbal / pharmacology*
  • Glucose / pharmacology
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism
  • Saponins / pharmacology*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*
  • Transcription Factor RelA / metabolism*
  • Triterpenes / pharmacology*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • Drugs, Chinese Herbal
  • RNA, Messenger
  • Saponins
  • TLR4 protein, human
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • Triterpenes
  • Tumor Necrosis Factor-alpha
  • astragaloside A
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • Glucose