Pterostilbene exerts an anti-inflammatory effect via regulating endoplasmic reticulum stress in endothelial cells

Cytokine. 2016 Jan;77:88-97. doi: 10.1016/j.cyto.2015.11.006. Epub 2015 Nov 7.


Pterostilbene (PT), an analog of resveratrol, exerts a potent anti-inflammatory effect. However, the protective effects of PT against inflammation in endothelial cells have not been elucidated. Previous studies have confirmed that endoplasmic reticulum stress (ERS) plays an important role in regulating the pathological process of endothelial cell inflammation. In this study, we explored the effect of PT on the tumor necrosis factor-α (TNF-α)-induced inflammatory response in human umbilical vein endothelial cells (HUVECs) and elaborated the role of ERS in this process. TNF-α treatment significantly upregulated the levels of inflammation-related molecules in cell culture media, increased the adhesion of monocytes to HUVECs, and enhanced the expression of the MMP9 and ICAM proteins in HUVECs. Additionally, TNF-α potently increased ERS-related protein levels, such as GRP78 and p-eIF2α. However, PT treatment reversed the increased production of inflammatory cytokines and the adhesion of monocytes to HUVECs, as well as reduced the TNF-α-induced effects exerted by ERS-related molecules. Furthermore, thapsigargin (THA), an ERS inducer, attenuated the protective effect of PT against TNF-α-induced inflammation and ERS in HUVECs. Additionally, the downregulation of ERS signaling using siRNA targeting eIF2α and IRE1 not only inhibited ERS-related molecules but also simulated the therapeutic effects of PT on TNF-α-induced inflammation. In summary, PT treatment potently attenuates inflammation in vascular endothelial cells, which at least partly depends on the reduction of ERS.

Keywords: Anti-inflammatory; Endoplasmic reticulum stress; Endothelial cells; Pterostilbene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Blotting, Western
  • Cell Adhesion / drug effects
  • Cell Adhesion Molecules / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Endoplasmic Reticulum Stress / drug effects*
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Eukaryotic Initiation Factor-2 / genetics
  • Eukaryotic Initiation Factor-2 / metabolism
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Inflammation Mediators / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA Interference
  • Stilbenes / pharmacology*
  • Tumor Necrosis Factor-alpha / pharmacology
  • U937 Cells


  • Anti-Inflammatory Agents
  • Cell Adhesion Molecules
  • Eukaryotic Initiation Factor-2
  • Inflammation Mediators
  • Stilbenes
  • Tumor Necrosis Factor-alpha
  • pterostilbene
  • ERN1 protein, human
  • Protein-Serine-Threonine Kinases
  • Endoribonucleases
  • Matrix Metalloproteinase 9