Curcumin ameliorates asthmatic airway inflammation by activating nuclear factor-E2-related factor 2/haem oxygenase (HO)-1 signalling pathway

Clin Exp Pharmacol Physiol. 2015 May;42(5):520-9. doi: 10.1111/1440-1681.12384.


Previous studies have shown that curcumin alleviates asthma in vivo. However, the relationship between curcumin and the nuclear factor-E2-related factor 2 (Nrf2)/haem oxygenase (HO)-1 pathway in asthma treatment remains unknown. The aim of the present study was to investigate the mechanisms of curcumin involved in the amelioration of airway inflammation in a mouse asthma model. Curcumin was administrated to asthmatic mice, and bronchoalveolar lavage fluid was collected. Inflammatory cell infiltration was measured by Giemsa staining. Immunoglobulin E production in bronchoalveolar lavage fluid was measured by enzyme-linked immunosorbent assay. Histological analyses were evaluated with haematoxylin-eosin and periodic acid-Schiff staining. Airway hyperresponsiveness was examined by whole-body plethysmography. Nuclear factor-E2-related factor 2, HO-1, nuclear factor-κB and inhibitory κB/p-inhibitory κB levels in lung tissues were detected by western blot, and Nrf2 activity was measured by electrophoretic mobility shift assay. Tumour necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in the small interfering RNA-transfected cells were detected by enzyme-linked immunosorbent assay. Curcumin treatment significantly reduced immunoglobulin E production, attenuated inflammatory cell accumulation and goblet cell hyperplasia, and ameliorated mucus secretion and airway hyperresponsiveness. Nuclear factor-E2-related factor 2 and HO-1 levels in lung tissues were significantly increased. Meanwhile, Nrf2 activity was enhanced. Nuclear factor-κB and p-inhibitory κB levels were elevated in the lung tissue of ovalbumin-challenged mice. Both were restored to normal levels after curcumin treatment. Haem oxygenase-1 and nuclear Nrf2 levels were enhanced in dose- and time-dependent manners in curcumin-treated RAW264.7 cells. Curcumin blocked lipopolysaccharide-upregulated expression of tumour necrosis factor-α, IL-1β, and IL-6. After the cells were transfected with HO-1 or Nrf2 small interfering RNA, lipopolysaccharide-induced pro-inflammation cytokine expression was significantly restored. In summary, curcumin might alleviate airway inflammation in asthma through the Nrf2/HO-1 pathway, potentially making it an effective drug in asthma treatment.

Keywords: Nrf2/HO-1 pathway; RAW264.7 cell; asthma; curcumin; pro-inflammation cytokine; siRNA.

MeSH terms

  • Animals
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / metabolism
  • Asthma / pathology*
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Cytokines / metabolism
  • Female
  • Gene Knockdown Techniques
  • Goblet Cells / drug effects
  • Goblet Cells / pathology
  • Heme Oxygenase-1 / deficiency
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Hyperplasia
  • Lipopolysaccharides / adverse effects
  • Lung / drug effects*
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology*
  • Mice
  • NF-E2-Related Factor 2 / deficiency
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Ovalbumin / immunology
  • RAW 264.7 Cells
  • RNA, Small Interfering / genetics
  • Signal Transduction / drug effects


  • Cytokines
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • RNA, Small Interfering
  • Ovalbumin
  • Heme Oxygenase-1
  • Curcumin