Salvianolic acid B improves airway hyperresponsiveness by inhibiting MUC5AC overproduction associated with Erk1/2/P38 signaling

Eur J Pharmacol. 2018 Apr 5:824:30-39. doi: 10.1016/j.ejphar.2018.01.050. Epub 2018 Jan 31.

Abstract

Salvianolic acid B (SalB) is one of the main water-soluble composites from Chinese medicine Dansen (Radix miltiorrhiza). It is used for clinical treatment of various diseases including cardiovascular, lung, Liver, renal and cancers. However, the effects of SalB to allergy induced airway mucin hypersecretion, inflammation and hyperresponsiveness (AHR) remains not clear. Overproduction of airway MUC5AC is a central effector of inflammation that is strongly associated with AHR in asthmatic attack. In this study, we investigated the anti-asthmatic activity and mechanism of SalB in a murine model and human epithelial cells by monitoring changes in mucin expression and secretion, airway inflammation, AHR, and signaling pathways. SalB was administered by intragastric administration (i.g) daily for a week, starting at 21 days after sensitization of ovalbumin (OVA). All examinations were performed 24h after the last antigen challenge. We found that treatments with SalB significantly inhibited increase in the tracheobronchial secretion, glycosaminoglycan levels, interleukin (IL)-13, IL-4, and IL-5 cytokines mRNA and protein expression, and decrease in mucociliary clearance in lung tissues. Histological results demonstrated that SalB attenuated OVA-induced eosinophil infiltration, airway goblet cell hyperplasia, and MUC5AC and MUC5B mRNA and protein expression in lung tissues. SalB exhibited protective effects against AHR in OVA-challenged animals. In vitro, SalB significantly inhibited IL-13-induced MUC5AC and MUC5B mRNA and protein expression in human epithelial cells. These effects were blocked by SalB by downregulating the Erk1/2 and P38 signaling pathways. Taken together, these data indicate that treatment with SalB may improve AHR by inhibiting MUC5AC overproduction.

Keywords: Airway hyperresponsiveness; Airway inflammation; Interleukin−13; MUC5AC; Mucin hypersecretion; Salvianolic acid B.

MeSH terms

  • Animals
  • Anti-Asthmatic Agents / pharmacology*
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / drug therapy
  • Asthma / metabolism
  • Benzofurans / pharmacology*
  • Benzofurans / therapeutic use
  • Bronchi / drug effects
  • Bronchi / metabolism
  • Cell Line
  • Female
  • Gene Expression Regulation / drug effects
  • Glycosaminoglycans / metabolism
  • Humans
  • Interleukin-13 / genetics
  • Interleukin-13 / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Mucin 5AC / biosynthesis*
  • Respiratory Hypersensitivity / drug therapy*
  • Respiratory Hypersensitivity / genetics
  • Respiratory Hypersensitivity / metabolism
  • Respiratory Hypersensitivity / pathology
  • Trachea / drug effects
  • Trachea / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Asthmatic Agents
  • Benzofurans
  • Glycosaminoglycans
  • Interleukin-13
  • Mucin 5AC
  • salvianolic acid B
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases