Curcumin, bisdemethoxycurcumin and dimethoxycurcumin complexed with cyclodextrins have structure specific effect on the paracellular integrity of lung epithelia in vitro

The phytochemical curcumin may improve translocation of the cystic fibrosis transmembrane regulatory (CFTR) protein in lung epithelium and therefore be helpful in the treatment of cystic fibrosis (CF) symptoms. However, previous studies often use commercial curcumin that is a combination of curcumin, demethoxycurcumin and bisdemethoxycurcumin which could affect the investigated cells differently. In the present study, we investigated the potential difference between curcumin, bisdemethoxycurcumin and dimethoxycurcumin on the epithelial tight junction complex, in the bronchial epithelial cell line VA10, by measuring transepithelial electrical resistance (TER), immunofluorescence and western blotting of tight junction proteins. The curcuminoids were complexed with hydroxypropyl-γ-cyclodextrin for increased solubility and stability. Curcumin (10 µg/ml) increased the TER significantly after 24 h of treatment while four times higher concentration of bisdemethoxycurcumin was required to obtain similar increase in TER as curcumin. Interestingly, dimethoxycurcumin did not increase TER. Curcumin clearly affected the F-actin structures both apically and basolaterally. These results begin to define possible effects of curcuminoids on healthy bronchial epithelia and shows that difference in the phenyl moiety structure of the curcuminoids influences the paracellular epithelial integrity.