Curcumin Improves Epithelial Barrier Integrity of Caco-2 Monolayers by Inhibiting Endoplasmic Reticulum Stress and...

Area of Science:

• Molecular Biology
• Cell Biology
• Gastroenterology

Background:

• Curcumin, a natural polyphenol, exhibits potential antioxidant, anti-inflammatory, and antiapoptotic properties.
• While therapeutic effects of curcumin on ulcerative colitis (UC) are suggested, its precise mechanism of action requires further elucidation.
• Intestinal epithelial barrier dysfunction and apoptosis are key factors in UC pathogenesis.

Purpose of the Study:

• To investigate the protective mechanisms of curcumin on intestinal epithelial barrier integrity using an in vitro coculture model.
• To evaluate the effects of curcumin on tight junction protein expression, cell apoptosis, oxidative stress, and endoplasmic reticulum stress (ERS) in intestinal cells.

Main Methods:

• Establishment of an in vitro coculture model using Caco-2 and differentiated THP-1 cells.
• Administration of curcumin (10 μM) and subsequent analysis via Western blot for tight junction proteins (ZO-1, claudin-1), oxidative stress markers (iNOS, γH2AX), and ERS-related molecules (CHOP, cleaved caspase-12).
• Assessment of Caco-2 cell apoptosis using Annexin V-APC/7-AAD assays and flow cytometry.

Main Results:

• Curcumin treatment significantly upregulated the protein levels of zonula occludens-1 (ZO-1) and claudin-1, enhancing intestinal epithelial barrier integrity.
• Curcumin administration markedly reduced Caco-2 cell apoptosis and downregulated key markers of oxidative stress (iNOS, γH2AX) and ERS-induced apoptosis (CHOP, cleaved caspase-12).
• Curcumin effectively inhibited the PERK-eIF2α-ATF4-CHOP signaling pathway, a critical mediator of ERS-induced apoptosis.

Conclusions:

• Curcumin enhances intestinal epithelial barrier function by upregulating tight junction proteins and mitigating apoptosis in an in vitro model.
• The protective effects of curcumin are potentially mediated through the suppression of endoplasmic reticulum stress and subsequent apoptosis.
• These findings provide mechanistic insights into curcumin's therapeutic potential for conditions like ulcerative colitis involving intestinal barrier dysfunction.