title: Suppression of adhesion molecule expression by phenanthrene-containing extract of bulbils of Chinese Yam in vascular smooth muscle cells through inhibition of MAPK, Akt and NF-κB.
abstract: Atherosclerosis is a chronic inflammatory disease associated with increased expression of adhesion molecules in vascular smooth muscle cells (VSMCs). The objective of this study was to examine the in vitro effects of extract from aerial Bulbil of Dioscorea batatas Decne (Db-Ex) on the ability to suppress the expression of adhesion molecules induced by TNF-α. We also identified bioactive components from a methanol extract. VSMCs pre-exposed to Db-Ex (10-100 μg/ml) were stimulated with TNF-α (10 ng/ml). Preincubation of VSMCs for 2 h with Db-Ex dose-dependently inhibited TNF-α-induced adhesion of THP-1 monocytic cells and mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Db-Ex treatment decreased ROS production and the amount of phosphorylated form of p38, ERK, JNK and Akt in TNF-α-stimulated cells, suggesting that Db-Ex inhibits adhesion molecule expression possibly through MAPK and Akt regulation. Db-Ex also suppressed TNF-α-activation NK-κB. This effect was mediated through degradation of IκBα and nuclear translocation of the p65 subunit of NF-κB. These results suggest that Db-Ex inhibits monocyte adhesion and the TNF-α-mediated induction of adhesion molecules in VSMC by downregulating the MAPK/Akt/NF-κB signaling pathway, which may explain the ability of Db-Ex to suppress inflammation within the atherosclerotic lesion.
authors.affiliation: Division of Immunopharmacolgy, School of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do 440-746, Republic of Korea.
authors.forename: Ko-Woon
authors.initials: KW
authors.lastname: Choi
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Um
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Kwak
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Kim
authors.forename: Eun-Yi
authors.initials: EY
authors.lastname: Moon
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Kwon
authors.forename: Suhkneung
authors.initials: S
authors.lastname: Pyo
mesh_terms: D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D017931:DNA Primers; D027742:Dioscorea / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010616:Phenanthrenes / Q000302:isolation & purification / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015815:Cell Adhesion Molecules; D017931:DNA Primers; D016328:NF-kappa B; D010616:Phenanthrenes; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C031181:phenanthrene; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases