Berberine Prevents NSAID-Induced Small Intestinal Injury by Protecting Intestinal Barrier and Inhibiting...

Area of Science:

• Gastroenterology
• Pharmacology
• Molecular Biology

Background:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) commonly cause gastrointestinal injuries, including small intestinal damage.
• Berberine (BBR), a traditional Chinese medicine, offers protection against NSAID-induced injuries, but its mechanism is not fully understood.

Purpose of the Study:

• To evaluate the protective effects of BBR against NSAID-induced intestinal injury.
• To elucidate the molecular mechanisms underlying BBR's protective action.

Main Methods:

• Utilized mouse models and human gut organoids to assess NSAID-induced intestinal injury.
• Administered indomethacin (NSAID) with or without BBR to mice.
• Exposed human gut organoids to NSAID with or without BBR.
• Performed histological analyses, cytokine measurements, and Western blotting.

Main Results:

• BBR treatment significantly reduced NSAID-induced ulcers and adhesions in mice.
• BBR preserved tight junction proteins (Claudin-1, Occludin, ZO-1) in the ileum.
• BBR inhibited inflammasome activation (NLRP6, NLRC4), reducing Caspase-1 maturation and downstream inflammatory cytokines.
• BBR mitigated NSAID-induced epithelial barrier disruption in human gut organoids.

Conclusions:

• BBR effectively prevents NSAID-induced small intestinal injury.
• BBR maintains tight junction integrity and inhibits inflammasome activation.
• BBR shows potential as a therapeutic agent for NSAID-induced gastrointestinal damage.