The ginger component 6-shogaol prevents TNF-α-induced barrier loss via inhibition of PI3K/Akt and NF-κB signaling

Scope: Anti-inflammatory properties of the ginger-derived pungent component 6-shogaol (6-SG) have been studied intensively in recent years. Purpose of this study was to characterize the influence of 6-SG on inflammation-related intestinal barrier dysfunction, especially its paracellular component. Methods and results: The effect of 6-SG was studied in the human intestinal cell models HT-29/B6 and Caco-2 either under control conditions or challenged by the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha). Electrophysiological measurements, freeze-fracture electron microscopy, and protein analyses were performed. 6-SG partially prevented both, the TNF-alpha-induced decrease in transepithelial resistance and the rise in fluorescein permeability. By inhibiting phosphatidylinositol-3-kinase/Akt signaling 6-SG prevented the TNF-alpha-induced increase in protein expression of claudin-2, a channel-forming tight junction protein. In addition, the TNF-alpha-induced disassembly of the sealing tight junction protein claudin-1 was attenuated, the latter of which was due to TNF-alpha-triggered phosphorylation of nuclear factor kappa light chain enhancer of activated B cells (NF-kappa B). Conclusion: 6-SG has barrier-protective effects by affecting TNF-alpha-induced claudin-2 upregulation and claudin-1 disassembly via inhibition of phoshatidylinositol-3-kinase/Akt and nuclear factor kappa light chain enhancer of activated B-cell signaling. Therefore, 6-SG-containing food might be beneficial for barrier preservation during intestinal inflammation.