L-tetrahydropalamatine inhibits tumor necrosis factor-α-induced monocyte-endothelial cell adhesion through downregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 involving suppression of nuclear factor-κ B signaling pathway

Chin J Integr Med. 2015 May;21(5):361-8. doi: 10.1007/s11655-015-2165-7. Epub 2015 Mar 17.

Abstract

Objective: To investigate whether I-tetrahydropalmatine (I-THP), an alkaloid mainly present in Corydalis family, could ameliorate early vascular inflammatory responses in atherosclerotic processes.

Methods: Fluorescently labeled monocytes were co-incubated with human umbilical vein endothelial cells (HUVECs), which were pretreated with I-THP and then simulated with tumor necrosis factor (TNF)-α in absence of I-THP to determine if I-THP could reduce thecytokine-induced adhesion of monocytes to HUVECs. Then I-THP were further studied the underlying mechanisms through observing the transcriptional and translational level of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the nuclear translocation of nuclear factor (NF)-κ B in HUVECs.

Results: L-THP could block TNF-α-induced adhesion of monocytes to HUVECs and could significantly inhibited the expression of ICAM-1 and VCAM-1 on cell surface by 31% and 36% at 30 μ mol/L. L-THP pretreatment could also markedly reduce transcriptional and translational level of VCAM-1 as well as mildly reduce the total protein and mRNA expression levels of ICAM-1. Furthermore, I-THP attenuated TNF-α-stimulated NF-κ B nuclear translocation.

Conclusion: These results provide evidences supporting that I-THP could be a promising compound in the prevention and treatment of the early vascular inflammatory reaction in atherosclerosis by inhibiting monocyte adhesion to vascular endothelial cell through downregulating ICAM-1 and VCAM-1 in vascular endothelial cell based on suppressing NF-κ B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Berberine Alkaloids / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Down-Regulation / drug effects*
  • Human Umbilical Vein Endothelial Cells / cytology*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Monocytes / cytology*
  • Monocytes / drug effects
  • Monocytes / metabolism
  • NF-kappa B / metabolism*
  • Protein Transport / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

  • Berberine Alkaloids
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • tetrahydropalmatine