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The ginger component 6‐shogaol prevents TNF‐α‐induced barrier loss via inhibition of PI3K/Akt and NF‐κB signaling
Author(s) -
Luettig Julia,
Rosenthal Rita,
Lee InFah M.,
Krug Susanne M.,
Schulzke Jörg D.
Publication year - 2016
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201600274
Subject(s) - protein kinase b , tight junction , tumor necrosis factor alpha , microbiology and biotechnology , chemistry , claudin , pi3k/akt/mtor pathway , barrier function , signal transduction , paracellular transport , inflammation , nfkb1 , biology , immunology , biochemistry , permeability (electromagnetism) , transcription factor , membrane , gene
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 α (TNF‐α). Electrophysiological measurements, freeze‐fracture electron microscopy, and protein analyses were performed. 6‐SG partially prevented both, the TNF‐α‐induced decrease in transepithelial resistance and the rise in fluorescein permeability. By inhibiting phosphatidylinositol‐3‐kinase/Akt signaling 6‐SG prevented the TNF‐α‐induced increase in protein expression of claudin‐2, a channel‐forming tight junction protein. In addition, the TNF‐α‐induced disassembly of the sealing tight junction protein claudin‐1 was attenuated, the latter of which was due to TNF‐α‐triggered phosphorylation of nuclear factor kappa light chain enhancer of activated B cells (NF‐κB). Conclusion 6‐SG has barrier‐protective effects by affecting TNF‐α‐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.