Luteolin alleviates ulcerative colitis through SHP-1/STAT3 pathway.

Area of Science:

• Gastroenterology
• Molecular Biology
• Pharmacology

Background:

• Luteolin is known to improve epithelial barrier integrity.
• The precise mechanism of Luteolin's action on the intestinal barrier remains unclear.
• This study investigates Luteolin's effects and regulatory mechanisms in intestinal epithelial barrier integrity.

Purpose of the Study:

• To explore the effects of Luteolin on intestinal epithelial barrier integrity.
• To elucidate the underlying regulatory mechanism of Luteolin's action.
• To evaluate Luteolin's therapeutic potential in ulcerative colitis.

Main Methods:

• Caco-2 cell monolayers were treated with TNF-α, IFN-γ, and Luteolin.
• SHP-1 (protein phosphoserine phosphatase-1) expression was manipulated (overexpression/knockdown).
• Barrier function was assessed using TEER and FITC-dextran assays, with molecular analysis via qRT-PCR and Western blot. An in vivo ulcerative colitis model was also used.

Main Results:

• Luteolin treatment increased Caco-2 monolayer resistance and expression of tight junction proteins (OCLN, CLDN1, ZO1), while decreasing CLDN2.
• Overexpression of SHP-1 enhanced epithelial barrier function; SHP-1 knockdown or STAT3 inhibition negated Luteolin's protective effects.
• Luteolin significantly alleviated symptoms in a DSS-induced mouse model of ulcerative colitis.

Conclusions:

• Luteolin treatment promotes intestinal epithelial barrier function.
• Luteolin preserves intestinal barrier integrity potentially by inhibiting the STAT3 signaling pathway through SHP-1.
• These findings highlight Luteolin as a potential therapeutic agent for intestinal barrier dysfunction.