Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune System

Int J Mol Sci. 2023 Mar 29;24(7):6419. doi: 10.3390/ijms24076419.


Inflammatory bowel disease (IBD) refers to chronic intestinal immune-mediated diseases including two main disease manifestations: ulcerative colitis (UC) and Crohn's disease (CD). Epidemiological, clinical, and preclinical evidence has highlighted the potential anti-inflammatory properties of naturally occurring alkaloids. In the present study, we investigated the potential anti-inflammatory activities of the tobacco alkaloids nicotine and anatabine in a dextran sulfate sodium (DSS)-induced UC mouse model with a fully humanized immune system. Our results show that nicotine significantly reduced all acute colitis symptoms and improved colitis-specific endpoints, including histopathologically assessed colon inflammation, tissue damage, and mononuclear cell infiltration. The tobacco alkaloid anatabine showed similar effectiveness trends, although they were generally weaker or not significant. Gene expression analysis in the context of biological network models of IBD further pinpointed a possible mechanism by which nicotine attenuated DSS-induced colitis in humanized mice. The current study enables further investigation of possible molecular mechanisms by which tobacco alkaloids attenuate UC symptoms.

Keywords: alkaloids; mouse model; nicotine; ulcerative colitis.

MeSH terms

  • Alkaloids* / metabolism
  • Alkaloids* / pharmacology
  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Antineoplastic Agents* / therapeutic use
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / metabolism
  • Colon / metabolism
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Immune System / metabolism
  • Inflammatory Bowel Diseases* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nicotiana / adverse effects
  • Nicotine / adverse effects


  • Nicotine
  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Alkaloids
  • Dextran Sulfate

Grants and funding

Philip Morris International is the sole source of funding and the sponsor of this research.