DK-1108 exerts anti-inflammatory activity against phorbol 12-myristate 13-acetate-induced inflammation and protective effect against OVA-induced allergic asthma

Biomed Pharmacother. 2020 Dec:132:110950. doi: 10.1016/j.biopha.2020.110950. Epub 2020 Nov 3.

Abstract

There is an increasing interest in natural products and their derivatives with therapeutic benefits and less side effects compared to steroid therapy. Benzofuran derivatives display biological effects including anti-inflammatory effects. The present study aims to investigate whether (3-(7-methoxy-2-p-tolyl benzofuran-5-yl) propan-1-ol) (DK-1108), new synthetic benzofuran compound exerts anti-asthmatic effects in vitro and in vivo. DK-1108 strongly reduced the production of inflammatory mediators, cytokines and chemokines in RAW264.7 and A549 cells. DK-1108 significantly regulated the levels of AKT/MAPKs/c-Jun activation, AP-1 luciferase activity and ICAM-1 expression. Furthermore, DK-1108 effectively suppressed the adhesion of A549 and EOL-1 cells. In OVA-induced asthmatic mice, DK-1108 decreased the levels of IL-5/IL-13/IgE production, eosinophils/macrophages influx, ICAM-1/MCP-1 expression, mucus secretion and airway hyperresponsiveness (AHR). These effects of DK-1108 were accompanied by downregulation of MAPKs activation. Therefore, we suggest that DK-1108 exerts protective effect against airway inflammation and mucus overproduction, and therefore could be valuable therapeutic agent for treatment in asthma.

Keywords: Asthma; DK-1108; ICAM-1; Inflammation; MAPK; Th2 cytokines.

MeSH terms

  • A549 Cells
  • Animals
  • Anti-Asthmatic Agents / chemistry
  • Anti-Asthmatic Agents / pharmacology
  • Anti-Asthmatic Agents / therapeutic use
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Asthma / chemically induced
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Benzofurans / chemistry
  • Benzofurans / pharmacology
  • Benzofurans / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / toxicity*
  • RAW 264.7 Cells
  • Respiratory Hypersensitivity / chemically induced
  • Respiratory Hypersensitivity / drug therapy*
  • Respiratory Hypersensitivity / metabolism
  • Tetradecanoylphorbol Acetate / analogs & derivatives*
  • Tetradecanoylphorbol Acetate / toxicity

Substances

  • Anti-Asthmatic Agents
  • Anti-Inflammatory Agents
  • Benzofurans
  • Inflammation Mediators
  • 4-O-methyl-12-O-tetradecanoylphorbol 13-acetate
  • Ovalbumin
  • Tetradecanoylphorbol Acetate