Protective effects of ambroxol in psoriasis like skin inflammation: Exploration of possible mechanisms

Int Immunopharmacol. 2019 Jun;71:301-312. doi: 10.1016/j.intimp.2019.03.035. Epub 2019 Mar 29.

Abstract

The purpose of this study was to investigate the protective effects of ambroxol in psoriasis-like skin inflammation both in vitro and in vivo and delineate the molecular mechanism of ambroxol. Our data demonstrated that ambroxol has an imperative role in inhibiting the lipopolysaccharide (LPS) stimulated nitrite levels, total cellular and mitochondrial reactive oxygen species level which was determined by Griess assay, DCFDA, and MitoSOX Red staining, respectively. We found that ambroxol remarkably reduced imiquimod (IMQ) induced epidermal hyperplasia, psoriasis area and severity index (PASI) scoring, splenomegaly, skin, and ear fold thickness. In addition, the histopathological evaluation revealed that ambroxol topical and subcutaneous treatment eloquently reduced psoriasiform lesions including acanthosis. Moreover, with ambroxol intervention, the levels of antioxidants glutathione (GSH), superoxide dismutase (SOD), and IL-10 were found to be increased along with a reduction in nitrite levels in skin tissues. On the other hand, ambroxol treatment significantly reduced imiquimod-induced levels of inflammatory cytokines such as IL-1β, IL-6, IL-17, IL-22, IL-23, TGF-β, and TNF-α. Furthermore, from immunoblotting, we found a decrease in the protein expression of nitrotyrosine, iNOS, NF-κB and MAPKs signaling cascade with a concomitant increase in the expression of Nrf-2 and SOD-1 in RAW 264.7 cells and skin tissues by ambroxol. Similar findings were observed by immunofluorescence in macrophages. Moreover, ambroxol downregulated the ICAM-1 and Ki67 expression observed in skin tissues. Collectively, our results demonstrate that ambroxol may have intriguing therapeutic possibilities in attenuating psoriasis.

Keywords: Ambroxol; Imiquimod; Lipopolysaccharide; Oxidative-nitrosative stress; Psoriasis.

MeSH terms

  • Ambroxol / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Hyperplasia
  • Imiquimod
  • Inflammation / drug therapy*
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / immunology
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Oxidative Stress / drug effects
  • Psoriasis / drug therapy*
  • RAW 264.7 Cells
  • Signal Transduction
  • Skin / pathology*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Ambroxol
  • Imiquimod