title: Isobavachalcone attenuates lipopolysaccharide-induced ICAM-1 expression in brain endothelial cells through blockade of toll-like receptor 4 signaling pathways.
abstract: Inflammation has been implicated in the pathogenesis of various cerebral diseases. Thus, control of brain inflammation is regarded as one of the important therapeutic strategies for the treatment of neurodegenerative diseases such as Alzheimer׳s disease and stroke. Isobavachalcone, a flavonoid from Psoralea corylifolia, is known to possess a wide spectrum of biological activities and is expected to be useful in preventing or treating neurodegenerative diseases. However, very little is known regarding its effects on cerebral inflammation. In this study, we examined the effect of isobavachalcone on leukocyte adhesion and intercellular adhesion molecule-1 (ICAM-1) expression in brain endothelial cells activated with lipopolysaccharide (LPS) and explored the possible mechanisms involved. Isobavachalcone significantly down-regulated LPS-induced ICAM-1 expression and leukocyte-endothelial cell adhesion and suppressed NF-κB activity which is implicated in the expression of ICAM-1. It attenuated ICAM-1 expression as well as NF-κB transcriptional activity induced by macrophage-activating lipopeptide 2-kDa (MALP-2) or polyriboinosinic polyribocytidylic acid (poly[I:C]). Isobavachalcone also down-regulated LPS or poly[I:C]-induced expression of IFN-β, which can indirectly activate NF-κB. These data imply that isobavachalcone can modulate both MyD88-dependent and TRIF-dependent signaling of toll-like receptor 4 (TLR4). Taken together, our data suggest that isobavachalcone inhibits LPS-induced ICAM-1 expression and leukocyte adhesion to brain endothelial cell by blocking TLR4 signaling and thus, has the potential to ameliorate neuronal injury in brain diseases associated with inflammation.
authors.affiliation: Department of Physiology, School of Medicine, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Kwang Min
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Physiology, School of Medicine, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Jae Mi
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Physiology, School of Medicine, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Baik
authors.affiliation: College of Pharmacy, Sookmyung Women׳s University, Seoul 140-742,Republic of Korea.
authors.forename: Jae Ha
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Physiology, School of Medicine, Ajou University, Suwon 443-749, Republic of Korea. Electronic address: shwanlee@ajou.ac.kr.
authors.forename: Soo Hwan
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D055666:Lipopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors*
chemical_list: D047188:Chalcones; D015850:Interleukin-6; D055666:Lipopeptides; D008070:Lipopolysaccharides; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D018799:Intercellular Adhesion Molecule-1; C468754:isobavachalcone; C106335:macrophage stimulatory lipopeptide 2; D011070:Poly I-C
keywords: Brain endothelial cell; Inflammation; Intercellular adhesion molecule-1; Isobavachalcone; Nuclear factor-κB; Toll-like receptor 4