Inhibition of endothelial cell adhesion by the new anti-inflammatory agent alpha-iso-cubebene.

The current study explored if alpha-iso-cubebene, a novel cubebene sesquiterpene compound purified from Schisandra chinensis, could attenuate the activities of adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells (HUVECs). The study was performed on HUVECs that were pretreated with 25 microg/ml of alpha-iso-cubebene before TNF-alpha treatment. Treatment of HUVECs with alpha-iso-cubebene for 6 h significantly inhibited TNF-alpha-induced reactive oxygen species (ROS) formation. HUVECs treated with alpha-iso-cubebene showed markedly suppressed TNF-alpha-induced mRNA expression of VCAM-1 and E-selectin, but little alteration in ICAM-1 mRNA expression. alpha-iso-Cubebene treatment also significantly decreased the TNF-alpha-induced cell surface and total protein expression of VCAM-1 and E-selectin without affecting ICAM-1 expression. In addition, treatment of HUVECs with alpha-iso-cubebene markedly reduced U937 monocyte adhesion to TNF-alpha-stimulated HUVECs. alpha-iso-Cubebene treatment did not affect translocation of NF-kappaB transcription factor from the cytosol into the nucleus. However, alpha-iso-cubebene significantly inhibited NF-kappaB transcription factor activation in TNF-alpha-stimulated HUVECs. The new anti-inflammatory agent alpha-iso-cubebene attenuates TNF-alpha-stimulated endothelial adhesion to monocytes by inhibiting intracellular ROS production, the activation of redox-sensitive NF-kappaB transcription factor and expression of VCAM-1 and E-selectin. Based on these findings, alpha-iso-cubebene is proposed as an effective new anti-inflammatory agent that may have a potential therapeutic use for the prevention and treatment of vascular diseases.

CDNA array analysis of gene expression profiles in brain of mice exposed to manganese.

This study is performed to detect changes of gene expression in substantia nigra (SN) and striatum in manganese (Mn)-exposed mice brain. The cDNA array is a recently developed molecular biological method that can detect the differential expression of several hundreds of genes simultaneously and is therefore advantageous in the study of trace metal intoxication effect at the genetic level. Using this technology, we discovered 5 genes in the mouse striatum and 9 genes in SN changed by more than 50% following Mn exposure. Depression were observed in two genes (neural cell adhesion protein BIG2, heavy neurofilament subunit genes) in striatum and three genes (light neurofilament subunit, brain acyl-CoA synthetase II, heavy neurofilament subunit genes) in the SN. However three genes (N-acetylglucosaminyltransferase I, S100beta, and synaptonemal complex protein I genes) in striatum and six genes (noggin, striatin, Ost oncogene, S100beta, calcium/calmodulin-dependent protein kinase kinase beta, and N-acetylglucosaminyltransferase I genes) in SN were elevated following Mn exposure. Immunohistochemical study revealed that protein levels of S100beta also increased following Mn treatment. Activated astrocytes overexpressing S100beta are invariably and intimately associated with decreased expression of heavy and light neurofilament subunits which is a distinguishing feature of neurodegeneration by Mn exposure. All our findings suggested that neuronal degenerations occur in SN as well as striatum of mice exposed to Mn.