title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Bin-rui
authors.initials: BR
authors.lastname: Yang
authors.forename: Nan
authors.initials: N
authors.lastname: Yu
authors.forename: Yan-hui
authors.initials: YH
authors.lastname: Deng
authors.forename: Pui Man
authors.initials: PM
authors.lastname: Hoi
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Guang-yu
authors.initials: GY
authors.lastname: Liu
authors.forename: Wei-hong
authors.initials: WH
authors.lastname: Cong
authors.forename: Simon Ming-yuen
authors.initials: SM
authors.lastname: Lee
mesh_terms: D001600:Berberine Alkaloids / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D001600:Berberine Alkaloids; D016328:NF-kappa B; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C014215:tetrahydropalmatine