Red wine polyphenol extract efficiently protects intestinal epithelial cells from inflammation via opposite...

Area of Science:

• Gastroenterology and Immunology
• Molecular Biology
• Nutritional Science

Background:

• Intestinal inflammation requires novel therapeutic strategies with improved safety and efficacy.
• Dietary polyphenols show promise for chronic inflammatory diseases, but their mechanisms are not fully understood.
• Red wine extract (RWE) is a readily available source of polyphenols.

Purpose of the Study:

• To elucidate the molecular mechanisms of the anti-inflammatory effects of a non-alcoholic red wine extract (RWE).
• To investigate RWE's action on the Janus kinase/signal transducer and activator of transcription (JAK/STAT) and Nuclear factor-erythroid 2-related factor-2 (Nrf2) pathways in intestinal inflammation.

Main Methods:

• Treatment with RWE in an in vitro model of intestinal inflammation.
• Analysis of key signaling molecules including phosphorylated STAT1, phosphorylated JAK1, and nuclear Nrf2.
• Measurement of downstream targets like heme oxygenase-1 (HO-1) and glutamate-cysteine ligase subunit catalytic (GCLc) gene expression.
• Assessment of glutathione (GSH) synthesis.

Main Results:

• RWE significantly reduced the nuclear levels of phosphorylated STAT1 and cellular levels of phosphorylated JAK1, suppressing the JAK/STAT inflammatory cascade.
• RWE increased nuclear Nrf2 levels, activating the Nrf2 pathway.
• RWE upregulated HO-1 expression and GCLc gene expression, enhancing GSH synthesis and counteracting inflammatory GSH depletion.

Conclusions:

• RWE exerts anti-inflammatory effects through complementary mechanisms: suppression of the JAK/STAT pathway and activation of the Nrf2 pathway.
• These findings support the potential of RWE as an accessible and inexpensive therapeutic agent for gastrointestinal inflammation.
• RWE demonstrates a dual action, mitigating inflammatory signaling while bolstering cellular antioxidant defenses.