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Aegeline attenuates TNBS-induced colitis by suppressing the NFƙB-mediated NLRP3 inflammasome pathway in mice

Bhagyabhumi Shah1, Nilay Solanki2

  • 1Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology (CHARUSAT), CHARUSAT Campus, Changa, 388421, Gujarat, India. Bhagyabhumishah.ph@charusat.ac.in.

Inflammopharmacology
|May 20, 2024
PubMed

Insights

Aegeline, derived from Aegle marmelos, effectively reduced inflammation and colon damage in a mouse model of ulcerative colitis (UC). This natural compound shows promise as a safer, more effective treatment for UC by targeting key inflammatory pathways.

Area of Science:

  • Pharmacology
  • Gastroenterology
  • Natural Products Chemistry

Background:

  • Ulcerative colitis (UC) management is challenging due to limited efficacy and side effects of current therapies.
  • Aegeline, an alkaloid from Aegle marmelos, possesses anti-inflammatory and antioxidant properties.
  • Aegeline's potential to suppress pro-inflammatory cytokines warrants investigation for UC treatment.

Purpose of the Study:

  • To investigate the therapeutic potential of aegeline in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mouse model.
  • To elucidate the mechanism of action involving the NF-κB-mediated NLRP3 inflammasome pathway.

Main Methods:

  • Induction of colitis in mice using TNBS.
  • Administration of varying doses of aegeline (5, 10, 20 mg/kg) or sulfasalazine.
  • Assessment of physical parameters, disease activity index (DAI), myeloperoxidase (MPO), nitric oxide (NO), gene expression, and histopathology.

Main Results:

  • Aegeline (10, 20 mg/kg) significantly improved physical parameters and reduced DAI and MPO levels.
  • High-dose aegeline downregulated key inflammatory genes: NF-κB, iNOS, COX-2, NLRP3, IL-1β, and IL-18.
  • Histopathological analysis confirmed reduced colon damage in aegeline-treated groups.

Conclusions:

  • Aegeline demonstrates significant anti-inflammatory potential in TNBS-induced colitis.
  • Aegeline effectively protects the colon by downregulating inflammatory mediators via the NF-κB-mediated NLRP3 inflammasome pathway.
  • Aegeline represents a promising therapeutic candidate for ulcerative colitis treatment.
Keywords:
AegelineInflammatory bowel diseaseNFƙB pathwayNLRP3 inflammasomeUlcerative colitis

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