Purpose: Myrrh, the oleo-gum resin of Commiphora molmol, is well known for its anti-inflammatory properties. In different animal models, it protected against DSS-, TNBS- and oxazolone-induced colitis. To date, no information concerning the effect of myrrh on barrier properties are available. Thus, this study investigates the effect of myrrh on paracellular barrier function in the absence or presence of the pro-inflammatory cytokine TNFα.
Methods: Monolayers of human colon cell lines HT-29/B6 and Caco-2 were incubated with myrrh under control conditions or after challenge with the pro-inflammatory cytokine TNFα. Barrier function was analysed by electrophysiological and permeability measurements, Western blotting, immunostaining in combination with confocal microscopy, and freeze-fracture electron microscopy.
Results: In Caco-2 cells, myrrh induced an increase in transepithelial resistance (TER) which was associated with downregulation of the channel-forming tight junction (TJ) protein claudin-2 via inhibition of the PI3 kinase signalling pathway. In HT-29/B6 cells, myrrh had no effect on barrier properties under basic conditions, but protected against barrier damage induced by TNFα, as indicated by a decrease in TER and an increase in fluorescein permeability. The TNFα effect was associated with a redistribution of the sealing TJ protein claudin-1, an increase in the expression of claudin-2 and a change in TJ ultrastructure. Most importantly, all TNFα effects were inhibited by myrrh. The effect of myrrh on claudin-2 expression in this cell line was mediated via inhibition of the STAT6 pathway.
Conclusions: This study shows for the first time that myrrh exerts barrier-stabilising and TNFα-antagonising effects in human intestinal epithelial cell models via inhibition of PI3K and STAT6 signalling. This suggests therapeutic application of myrrh in intestinal diseases associated with barrier defects and inflammation.
Keywords: Channel-forming claudin-2; Myrrh; Paracellular permeability; Sealing claudin-1; TNFα; Tight junction.