title: Honokiol ameliorates endothelial dysfunction through suppression of PTX3 expression, a key mediator of IKK/IκB/NF-κB, in atherosclerotic cell model.
abstract: Pentraxin 3 (PTX3) was identified as a marker of the inflammatory response and overexpressed in various tissues and cells related to cardiovascular disease. Honokiol, an active component isolated from the Chinese medicinal herb Magnolia officinalis, was shown to have a variety of pharmacological activities. In the present study, we aimed to investigate the effects of honokiol on palmitic acid (PA)-induced dysfunction of human umbilical vein endothelial cells (HUVECs) and to elucidate potential regulatory mechanisms in this atherosclerotic cell model. Our results showed that PA significantly accelerated the expression of PTX3 in HUVECs through the IκB kinase (IKK)/IκB/nuclear factor-κB (NF-κB) pathway, reduced cell viability, induced cell apoptosis and triggered the inflammatory response. Knockdown of PTX3 supported cell growth and prevented apoptosis by blocking PA-inducted nitric oxide (NO) overproduction. Honokiol significantly suppressed the overexpression of PTX3 in PA-inducted HUVECs by inhibiting IκB phosphorylation and the expression of two NF-κB subunits (p50 and p65) in the IKK/IκB/NF-κB signaling pathway. Furthermore, honokiol reduced endothelial cell injury and apoptosis by regulating the expression of inducible NO synthase and endothelial NO synthase, as well as the generation of NO. Honokiol showed an anti-inflammatory effect in PA-inducted HUVECs by significantly inhibiting the generation of interleukin-6 (IL-6), IL-8 and monocyte chemoattractant protein-1. In summary, honokiol repaired endothelial dysfunction by suppressing PTX3 overexpression in an atherosclerotic cell model. PTX3 may be a potential therapeutic target for atherosclerosis.
authors.affiliation: Geriatrics Department, Shanghai Clinical Center, Chinese Academy of Sciences/Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Geriatrics Department, Shanghai Clinical Center, Chinese Academy of Sciences/Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.affiliation: Geriatrics Department, Shanghai Clinical Center, Chinese Academy of Sciences/Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Siyang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Shanghai Clinical Center, Chinese Academy of Sciences/Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Shuijun
authors.initials: S
authors.lastname: Li
authors.affiliation: Endocrinology Department, Shanghai Clinical Center, Chinese Academy of Sciences/Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Shanghai Clinical Center, Chinese Academy of Sciences/Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Wu
authors.affiliation: Geriatrics Department, Shanghai Clinical Center, Chinese Academy of Sciences/Shanghai Xuhui Central Hospital, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001713:Biphenyl Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000235:genetics* / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000276:immunology*; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry; D019308:Palmitic Acid; D017346:Protein Serine-Threonine Kinases / Q000276:immunology*; D000683:Serum Amyloid P-Component / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D000097782:NF-kappaB-Inducing Kinase; D000099153:Pentraxins; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D002097:C-Reactive Protein; D004365:Drugs, Chinese Herbal; D051550:I-kappa B Kinase; D017705:Lignans; D019308:Palmitic Acid; D017346:Protein Serine-Threonine Kinases; D000683:Serum Amyloid P-Component; D000097782:NF-kappaB-Inducing Kinase; D000099153:Pentraxins; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols