Anti- trachea inflammatory effects of diosgenin from Dioscorea nipponica through interactions with glucocorticoid receptor α

J Int Med Res. 2017 Feb;45(1):101-113. doi: 10.1177/0300060516676724. Epub 2016 Dec 7.

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.

Keywords: Diosgenin; asthma; glucocorticoid; glucocorticoid receptor.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology
  • Animals
  • Anti-Asthmatic Agents / isolation & purification
  • Anti-Asthmatic Agents / pharmacology*
  • Asthma / chemically induced
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / pathology
  • Dexamethasone / pharmacology
  • Dioscorea / chemistry*
  • Diosgenin / isolation & purification
  • Diosgenin / pharmacology*
  • Disease Models, Animal
  • Dual Specificity Phosphatase 1 / genetics
  • Dual Specificity Phosphatase 1 / immunology
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Epithelial Cells / pathology
  • Female
  • Gene Expression Regulation
  • Glucocorticoids / pharmacology
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / immunology
  • Humans
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Ovalbumin
  • Plant Extracts / chemistry
  • Primary Cell Culture
  • Receptors, Glucocorticoid / agonists*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / immunology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / pathology
  • Secretory Leukocyte Peptidase Inhibitor / genetics
  • Secretory Leukocyte Peptidase Inhibitor / immunology
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Anti-Asthmatic Agents
  • Dsip1 protein, mouse
  • Glucocorticoids
  • HSP70 Heat-Shock Proteins
  • IL1B protein, mouse
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • Plant Extracts
  • Receptors, Glucocorticoid
  • Secretory Leukocyte Peptidase Inhibitor
  • Slpi protein, mouse
  • TTP protein, mouse
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • glucocorticoid receptor alpha
  • interleukin-6, mouse
  • Dexamethasone
  • Ovalbumin
  • Dual Specificity Phosphatase 1
  • Dusp1 protein, mouse
  • Diosgenin