Celastrol Alleviates Intestinal Epithelial Permeability by Inhibiting Ferroptosis through PI3K/Akt/FOXO1/HO-1...

Area of Science:

• Gastroenterology
• Cell Biology
• Pharmacology

Background:

• Ulcerative colitis (UC) involves inflammation, epithelial cell death, and barrier damage.
• Understanding UC pathogenesis is crucial for developing effective treatments.

Purpose of the Study:

• To investigate celastrol's role in ferroptosis and intestinal epithelial barrier permeability.
• To explore celastrol's therapeutic potential for ulcerative colitis.

Main Methods:

• In vitro studies using RSL3-induced intestinal epithelial cells.
• In vivo studies using dextran sulfate sodium (DSS)-induced colitis model in mice.
• Analysis of ferroptosis-related proteins, tight junction proteins, and signaling pathways (Akt/FOXO1).

Main Results:

• Celastrol inhibited ferroptosis and improved intestinal epithelial barrier permeability by upregulating tight junction proteins (ZO-1, occludin, claudin-1).
• Celastrol attenuated RSL3-induced Akt/FOXO1 phosphorylation.
• In vivo, celastrol ameliorated DSS-induced colitis, reducing inflammation, mucosal damage, and colon shortening.

Conclusions:

• Celastrol demonstrates therapeutic potential for ulcerative colitis by targeting ferroptosis and enhancing intestinal barrier integrity.
• Celastrol's mechanism involves regulating ferroptosis and tight junction proteins via the PI3K/Akt pathway.