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Modulation of mTOR, NLRP3, and Nrf2/HO-1 signaling by atorvastatin and nitazoxanide in experimental ulcerative

Hayam Ali AlRasheed1, Mahmoud S Abdallah2, Esraa M Mosalam2,3

  • 1Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, 11671, Riyadh, Saudi Arabia.

Naunyn-Schmiedeberg'S Archives of Pharmacology
|March 27, 2026
PubMed

Insights

Atorvastatin and nitazoxanide show promise in treating ulcerative colitis (UC) by reducing inflammation and oxidative stress. These drugs effectively modulated key signaling pathways involved in UC pathogenesis in an experimental rat model.

Area of Science:

  • Gastroenterology
  • Pharmacology
  • Molecular Biology

Background:

  • Ulcerative colitis (UC) etiology is complex, involving multiple signaling pathways like IL-6/STAT3, Wnt, HO-1/Nrf2, AMPK, mTOR, and NLRP3.
  • Atorvastatin and nitazoxanide possess anti-inflammatory, antioxidant, and immunomodulatory properties potentially targeting these UC-related pathways.

Purpose of the Study:

  • To investigate the coloprotective effects of atorvastatin and nitazoxanide in an experimental model of UC.
  • To assess the impact of these drugs on key signaling pathways and inflammatory markers in colitis.

Main Methods:

  • Ulcerative colitis was induced in rats using acetic acid (AA).
  • Rats were treated with atorvastatin or nitazoxanide.
  • Disease severity was evaluated through colon length, weight, disease activity index, and histopathology.
  • Tissue levels of specific proteins (SIRT1, mTOR, HO-1, Nrf2, STAT3, AMPK, DKK1) and gene expression (NLRP3, Wnt, IL-6, TNF-α, DKK1) were measured.

Main Results:

  • AA-induced colitis resulted in significant colon damage.
  • Both atorvastatin and nitazoxanide treatment significantly reduced disease activity and improved histological scores.
  • Treated groups showed decreased expression of mTOR, NLRP3, DKK1, IL-6, TNF-α, and STAT3.
  • Conversely, HO-1, Nrf2, SIRT1, Wnt, and AMPK levels were upregulated by both drugs.

Conclusions:

  • Atorvastatin and nitazoxanide demonstrate significant coloprotective effects in experimental UC.
  • These agents ameliorate colitis by modulating inflammatory and oxidative stress pathways, including those involving mTOR, NLRP3, and Nrf2.
  • The findings suggest potential therapeutic roles for atorvastatin and nitazoxanide in managing UC.
Keywords:
AtorvastatinIL-6/STAT3/WntMTOR/NLRP3NitazoxanideNrf2Ulcerative colitis

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