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

Abstract

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.

Curcumin analogs (B2BrBC and C66) supplementation attenuates airway hyperreactivity and promote airway relaxation in neonatal rats exposed to hyperoxia

“…There are several mechanisms described for CUR derivatives to exercise their antiinflammatory activity. Liu et al (2015), reported that derivatives of CUR might alleviate airway inflammation in asthma through the Nrf2/HO-1 pathway. Other studies suggest that intranasal CUR (2.5 and 5.0 mg/ kg) regulates airway inflammation and airway obstruction by modulating cytokine levels (IL-4, IL-5, IFN-α, and TNF-α) and sPLA2 activity thereby inhibiting PGD 2 release and COX-2 expression (Kumari, Dash, & Singh, 2017;Masella, Di Benedetto, Varì, Filesi, & Giovannini, 2005;Subhashini, Chauhan, Dash, Paul, & Singh, 2016).…”

Nutritional control of IL-23/Th17-mediated autoimmune disease through HO-1/STAT3 activation

“…7c,d). The expression of HO-1 is regulated by Nrf24849 and CUR activates this signaling pathway. Whole genome expression profiling unraveled that oral CUR feeding regulates more than 800 NRF2-dependent genes in vivo with a >2-fold induction or suppression.…”

TLR-7 agonist attenuates airway reactivity and inflammation through Nrf2-mediated antioxidant protection in a murine model of allergic asthma

“…Nrf2 has been shown to be protective in various inflammatory animal models (Cho et al, 2013;Liu et al, 2015;Rangasamy et al, 2005). Importance of Nrf2 is also strengthened by the fact is that its induction leads to transcription of many antioxidant genes which include hemeoxygenase 1, glutathione peroxidase and SOD (Eggler et al, 2008;Lee et al, 2008;Vijayan et al, 2011;Zhu et al, 2005).…”

“…Nrf2 is a transcription factor that is activated by ROS and responsible for detoxification through induction of various antioxidant genes (Lee and Yang, 2012;Liu et al, 2015;Spiess et al, 2013;Yao et al, 2007). One of the antioxidants that may be induced through Nrf2 is superoxide dismutase (SOD).…”