Berberine Protects Mice Against Dextran Sulfate Sodium-Induced Colitis by Activating mTORC1 Pathway

Area of Science:

• Immunology
• Pharmacology
• Gastroenterology

Background:

• Ulcerative colitis is a chronic inflammatory condition with limited treatment options.
• Berberine, a plant alkaloid, shows potential in protecting against colitis, but its mechanism is not fully understood.
• Regulatory T cells (Treg cells) play a crucial role in immune homeostasis and suppressing inflammation.

Purpose of the Study:

• To elucidate the anti-inflammatory mechanism of berberine in a mouse model of ulcerative colitis.
• To investigate the role of berberine in regulating immune cell populations and metabolic pathways.
• To determine the involvement of the mTORC1 pathway in berberine's protective effects.

Main Methods:

• Induction of colitis in mice using dextran sulfate sodium (DSS).
• Administration of berberine (50 mg/kg) via gavage.
• Flow cytometry to quantify Treg cells.
• Targeted metabolomics to analyze glutamine and glutamate metabolism.
• Western blotting to assess mTORC1 pathway activation (S6K1, 4EBP1).
• Inhibition of mTORC1 signaling using rapamycin.

Main Results:

• Berberine treatment significantly increased the proportion of Treg cells in DSS-induced colitis mice.
• Metabolomic analysis revealed the involvement of glutamine and glutamate metabolism.
• Berberine upregulated the expression of mTORC1 downstream effectors S6K1 and 4EBP1.
• Inhibition of mTORC1 with rapamycin abolished the protective effects of berberine on colon length, disease activity, and Treg cell proportion.

Conclusions:

• Berberine exerts protective effects against DSS-induced colitis.
• The anti-inflammatory action of berberine is mediated by the activation of the mTORC1 pathway.
• Berberine increases the proportion of Treg cells, contributing to its therapeutic efficacy in colitis.