Walnut Septum-Derived Aqueous Extract Alleviates Colitis Through Modulation of Gut Metabolism and Inflammatory...

Area of Science:

• Gastroenterology
• Immunology
• Pharmacology

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options.
• Food-derived functional ingredients offer potential therapeutic avenues for intestinal health.
• Diaphragma Juglandis Fructus (AED) is a byproduct of Juglans regia L. with potential anti-inflammatory properties.

Purpose of the Study:

• To evaluate the anti-colitis effects of AED.
• To elucidate the underlying mechanisms of AED's action in colitis.
• To explore AED as a functional ingredient for UC management.

Main Methods:

• In vitro: LPS-stimulated RAW264.7 macrophages.
• In vivo: Dextran sulfate sodium (DSS)-induced colitis mouse model.
• Analyses: Cytokine profiling, JAK/STAT signaling assessment, histological examination, tight junction protein analysis, transcriptomics, metabolomics, network pharmacology, and molecular docking.

Main Results:

• AED suppressed pro-inflammatory cytokine production and JAK1/STAT3 signaling in vitro.
• AED mitigated DSS-induced colonic injury, restored tight junction proteins, and improved epithelial barrier integrity in vivo.
• Integrated analyses revealed AED-associated alterations in arginine-polyamine and taurine-hypotaurine metabolism, with ACE and VWF identified as potential targets.

Conclusions:

• AED exhibits significant anti-colitis effects.
• AED's efficacy is linked to modulation of inflammatory signaling, metabolic pathways, and barrier function.
• AED is a promising food-derived functional ingredient for ulcerative colitis management.