Curcumin attenuates allergic airway inflammation and hyper-responsiveness in mice through NF-κB inhibition.
J Ethnopharmacol. 2010 Jul 17. Epub 2010 Jul 17. PMID: 20643202
Central Research Institute, Choongwae Pharma Corp., Hwaseong 445-380, Republic of Korea.
ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a polyphenol compound from Curcuma longa L. has been used for centuries as an anti-inflammatory remedy including asthma. Curcumin has been reported to exert an anti-inflammatory effect, in part, through inhibition of the NF-kappaB pathway. AIM OF THE STUDY: The purposes of this study were to determine whether curcumin inhibits NF-kappaB-dependent transcription in vitro, and test whether treatment with curcumin reduces allergen-induced airway inflammation and hyper-responsiveness in a mouse model of asthma through inhibition of NF-kappaB pathway. MATERIALS AND METHODS: The effect of curcumin on NF-kappaB transcriptional activity was investigated using a cell-based luciferase reporter assay in A549 cells and by measuring inhibitory kappaBalpha (IkappaBalpha), p65, and p50 levels after exposure of Raw264.7 cells to lipopolysaccharide (LPS). BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection, and challenged with repeated exposure to aerosolized OVA. The effects of daily administered curcumin (200mg/kg body weight, i.p.) on airway hyper-responsiveness (AHR), inflammatory cell number, and IgE levels in bronchoalveolar lavage (BAL) fluid were analyzed. NF-kappaB activation in lung tissue was also assessed by Western blot analyses. RESULTS: Curcumin inhibited NF-kappaB-dependent transcription in reporter assays in A549 cells with an IC(50) of 21.50+/-1.25muM. Curcumin stabilized IkappaBalpha and inhibited nuclear translocation of p65 and p50 in LPS-activated Raw264.7 cells, and curcumin-treated mice showed reduced nuclear translocation of p65 in lung tissue. Treatment with curcumin significantly attenuated AHR and reduced the numbers of total leukocytes and eosinophils in BAL fluid. Infiltration of inflammatory cells and mucus occlusions in lung tissue were significantly ameliorated by treatment with curcumin, which also markedly decreased the level of IgE in BAL fluid. CONCLUSION: Curcumin attenuates the development of allergic airway inflammation and hyper-responsiveness, possibly through inhibition of NF-kappaB activation in the asthmatic lung tissue. Our results indicate that curcumin may attenuate development of asthma by inhibition of NF-kappaB activation.