title: Thymoquinone inhibits inflammation, neoangiogenesis and vascular remodeling in asthma mice.
abstract: Asthma is a chronic obstructive disease which is characterized by recurring airway inflammation, reversible airway obstruction, airway hyper responsiveness and vascular remodeling. Thymoquinone (TQ), an active ingredient isolated from Nigella sativa, was reported to exhibit anti-inflammation and anti-proliferation of in various cancer cells as well as epithelial cells. The aim of this study was to evaluate the effect of TQ on the inflammation, neoangiogenesis and vascular remodeling induced by Ovalbumin (OVA) in asthma mice in vivo and the anti-angiogenesis effects of TQ in VEGF-induced human umbilical vein endothelial cells (HUVECs) in vitro. Our results revealed that TQ inhibited the production of inflammatory factors interleukin-4/-5 (IL-4/-5) by enzyme-linked immunesorbent assay (ELISA). Immunohistochemistry analysis showed that the increase of platelet endothelial cell adhesion molecule-1, which is also known as CD31 and α-smooth muscle actinalpha (α-SMA) expression in asthma mice challenged by OVA was suppressed by TQ. Moreover, TQ suppressed the activation of VEGFR2-PI3K-Akt pathway and up-regulated the expression of Slit glycoprotein-2 (Slit-2) both in vivo and in vitro with the inhibition of tube information in HUVEC cells. Meanwhile immunofluorescence analysis showed that Slit-2 and Roundabout-4 (Robo-4) were co-expressing after TQ treatment in OVA-challenged asthma mice. Our study demonstrates that TQ attenuated the inflammatory reaction by antagonizing IL-4/-5 while the anti-neoangiogenesis effect of TQ is mediated by inhibition of vascular endothelial growth factor (VEGF) expression through VEGFR2/PI3K/Akt signaling pathway, which supports a potential role for TQ in ameliorating asthma.
authors.affiliation: Department of Respiratory Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China. Electronic address: xinming_med@126.com.
authors.forename: Xinming
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Respiratory Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Respiratory Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Yu
authors.affiliation: Department of Respiratory Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Kong
authors.affiliation: Department of Respiratory Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D016227:Benzoquinones / Q000627:therapeutic use*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000178:diet therapy / Q000188:drug therapy*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D031881:Nigella sativa / Q000276:immunology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D000098552:Slit Homolog 2 Protein
chemical_list: D016227:Benzoquinones; D036341:Intercellular Signaling Peptides and Proteins; D015848:Interleukin-5; D009419:Nerve Tissue Proteins; D042461:Vascular Endothelial Growth Factor A; D015847:Interleukin-4; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2; D051058:Oncogene Protein v-akt; C003466:thymoquinone; D000098552:Slit Homolog 2 Protein
keywords: Bronchial asthma; Ovalbumin; Robo-4; Slit-2; Thymoquinone; VEGF/PI3K/Akt