title: Anti- trachea inflammatory effects of diosgenin from Dioscorea nipponica through interactions with glucocorticoid receptor α.
abstract: Asthma is a heterogeneous disease characterized by symptoms of chronic inflammation and airway structural and functional changes. It affects about 300 million people worldwide and causes 250 000 deaths annually, but its symptoms can be greatly relieved by regular use of inhaled glucocorticoids (GCs). GCs exert their function through interacting with glucocorticoid receptors (GRs). Diosgenin is a naturally occurring steroidal saponin abundantly present in many medicinal plants, including Dioscorea nipponica, which shares a similar steroidal structure with GC. In this study, ovalbumin (OVA)-induced asthmatic mice and primary tracheal epithelial cells (TECs) were used as research models. ELISAs were applied to measure the secretion of TNF-α, IL-1β, and IL-6, while quantitative PCR and western blotting were applied to evaluate expression of GRs SLPI, TTP, GILZ, MKP-1, and NF-κB. Our data demonstrated that diosgenin suppressed the secretion of TNF-α, IL-1β, and IL-6 by enhancing the expression of GRs, SLPI, GILZ, and MKP-1, and inhibiting the expression of HSP70. These data provide some evidence on the molecular mechanism of diosgenin, which might facilitate its clinical applications.
authors.affiliation: 1 Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Junchao
authors.affiliation: 1 Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhen
authors.affiliation: 2 Department of Pulmonary Function, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Yuan
authors.affiliation: 3 Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liying
authors.affiliation: 1 Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Libin
authors.affiliation: 1 Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yuanhong
authors.affiliation: 2 Department of Pulmonary Function, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wei
authors.affiliation: 1 Department of Respiration, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Ruilin
authors.affiliation: 4 Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.
authors.forename: Zhai
authors.initials: Z
authors.lastname: Lu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D027742:Dioscorea / Q000737:chemistry*; D004144:Diosgenin / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin; D010936:Plant Extracts / Q000737:chemistry; D061251:Primary Cell Culture; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018927:Anti-Asthmatic Agents; D003907:Dexamethasone; D004144:Diosgenin; D054638:Dual Specificity Phosphatase 1; D005938:Glucocorticoids; D018840:HSP70 Heat-Shock Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D010047:Ovalbumin; D010936:Plant Extracts; D011965:Receptors, Glucocorticoid; D053481:Secretory Leukocyte Peptidase Inhibitor; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C498608:Dsip1 protein, mouse; C587672:IL1B protein, mouse; C506815:Slpi protein, mouse; C541099:TTP protein, mouse; C411470:glucocorticoid receptor alpha; C577686:interleukin-6, mouse; C517020:Dusp1 protein, mouse
keywords: Diosgenin; asthma; glucocorticoid; glucocorticoid receptor