Curcumin attenuates allergic airway inflammation and hyper-responsiveness in mice through NF-κB inhibition.
BACKGROUND
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-κB pathway.


OBJECTIVE
The purposes of this study were to determine whether curcumin inhibits NF-κB-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-κB pathway.


METHODS
The effect of curcumin on NF-κB transcriptional activity was investigated using a cell-based luciferase reporter assay in A549 cells and by measuring inhibitory κBα (IκBα), 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-κB activation in lung tissue was also assessed by Western blot analyses.


RESULTS
Curcumin inhibited NF-κB-dependent transcription in reporter assays in A549 cells with an IC(50) of 21.50±1.25μM. Curcumin stabilized IκBα 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.


CONCLUSIONS
Curcumin attenuates the development of allergic airway inflammation and hyper-responsiveness, possibly through inhibition of NF-κB activation in the asthmatic lung tissue. Our results indicate that curcumin may attenuate development of asthma by inhibition of NF-κB activation.
Oh
Se-Woong
SW
Central Research Institute, Choongwae Pharma Corp., Hwaseong, Republic of Korea.
Cha
Joo-Young
JY
Jung
Ji-Eun
JE
Chang
Beom-Chol
BC
Kwon
Hyo-Jung
HJ
Lee
Bo-Ram
BR
Kim
Dae-Yong
DY
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D020672:I-kappa B Proteins / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007962:Leukocytes / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D027343:Rhizome; D051996:Transcription Factor RelA / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D010936:Plant Extracts; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D007073:Immunoglobulin E; D003474:Curcumin