title: Acanthoic acid inhibits LPS-induced inflammatory response by activating LXRα in human umbilical vein endothelial cells.
abstract: Acanthoic acid, a pimaradiene diterpene isolated from Acanthopanax koreanum, has been reported to have anti-inflammatory activities. However, the effect of acanthoic acid on vascular inflammation has not been investigated. The aim of this study was to investigate the anti-inflammatory effects of acanthoic acid on lipopolysaccharide (LPS)-induced inflammatory response in human umbilical vein endothelial cells (HUVECs). The production of cytokines TNF-α and IL-8 was detected by ELISA. The expression of VCAM-1, ICAM-1, E-selectin, NF-κB and LXRα were detected by Western blotting. Adhesion of monocytes to HUVECs was detected by monocytic cell adhesion assay. The results showed that acanthoic acid dose-dependently inhibited LPS-induced TNF-α and IL-8 production. Acanthoic acid also inhibited TNF-α-induced IL-8 and IL-6 production. LPS-induced endothelial cell adhesion molecules, VCAM-1 and ICAM-1 were also inhibited by acanthoic acid. Acanthoic acid inhibited LPS-induced NF-κB activation. Furthermore, acanthoic acid dose-dependently up-regulated the expression of LXRα. In addition, our results showed that the anti-inflammatory effect of acanthoic acid was attenuated by transfection with LXRα siRNA. In conclusion, the anti-inflammatory effect of acanthoic acid is due to its ability to activate LXRα. Acanthoic acid may be a therapeutic agent for inflammatory cardiovascular disease.
authors.affiliation: Department of Cardiovascular Surgery, The Second Hospital of Shandong University, Jinan, Shangdong 250000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shangdong 250000, China.
authors.forename: Xiao-Shi
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The Second Hospital of Shandong University, Jinan, Shangdong 250000, China. Electronic address: yujinlongyl@sina.com.
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Yu
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D019040:E-Selectin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides; D000071518:Liver X Receptors; D016328:NF-kappa B / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D019040:E-Selectin; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D000071518:Liver X Receptors; D016328:NF-kappa B; D057093:Orphan Nuclear Receptors; D034741:RNA, Small Interfering; C546936:SELE protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C099958:acanthoic acid; D018799:Intercellular Adhesion Molecule-1
keywords: Acanthoic acid; Cytokine; Human umbilical vein endothelial cells; LXRα; NF-κB