α-Mangostin ameliorates dextran sulfate sodium-induced colitis through inhibition of NF-κB and MAPK pathways

Area of Science:

• Gastroenterology
• Immunology
• Pharmacology

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) affecting the colon.
• Previous research suggests alpha-mangostin (αMG) may inhibit nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), key inflammatory mediators.
• High colon distribution of αMG indicates potential therapeutic value for UC.

Purpose of the Study:

• To investigate the therapeutic efficacy of αMG in a mouse model of UC.
• To determine the effects of αMG on NF-κB and MAPK signaling pathways in colitis.
• To assess the colon distribution of αMG in the context of DSS-induced colitis.

Main Methods:

• Induction of colitis in mice using dextran sodium sulfate (DSS).
• Administration of αMG to DSS-induced colitis mice.
• Assessment of disease activity index, colon length, myeloperoxidase (MPO) activity, and histological changes.
• Evaluation of NF-κB and MAPK pathway activation via Western blotting for phosphorylated proteins.

Main Results:

• DSS-induced colitis mice exhibited increased disease activity, reduced colon length, elevated MPO activity, and significant histological damage.
• Inflammatory pathways, including NF-κB and MAPK signaling (phosphorylation of IκB kinase, ERK1/2, SAPK/JNK, p38), were activated in the colons of DSS mice.
• αMG treatment restored disease parameters, reduced inflammation, and normalized histological findings in DSS mice.
• αMG treatment led to decreased intestinal metabolism and increased colon distribution of αMG in DSS mice.

Conclusions:

• αMG effectively attenuated DSS-induced colitis in mice.
• The therapeutic effect of αMG is likely mediated by the inhibition of NF-κB and MAPK pathways in the colon.
• Increased colon distribution of αMG contributes to its anti-colitis effects.