Anatabine ameliorates intestinal inflammation and reduces the production of pro-inflammatory factors in a dextran sulfat
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(2020) 17:29
RESEARCH
Open Access
Anatabine ameliorates intestinal inflammation and reduces the production of pro-inflammatory factors in a dextran sulfate sodium mouse model of colitis Pedro A. Ruiz Castro1*† , Ulrike Kogel1†, Giuseppe Lo Sasso1†, Blaine W. Phillips2*†, Alain Sewer1†, Bjorn Titz1, Llenalia Garcia1, Athanasios Kondylis1, Emmanuel Guedj1, Dariusz Peric1, David Bornand1, Remi Dulize1, Celine Merg1, Maica Corciulo1, Nikolai V. Ivanov1, Manuel C. Peitsch1 and Julia Hoeng1*
Abstract Background: Inflammatory bowel disease (IBD) is the collective term for chronic immune-mediated diseases of unknown, multifactorial etiology, arising from the interplay between genetic and environmental factors and including two main disease manifestations: ulcerative colitis (UC) and Crohn’s disease. In the last few decades, naturally occurring alkaloids have gained interest because of their substantial anti-inflammatory effects in several animal models of disease. Studies on mouse models of IBD have demonstrated the anti-inflammatory action of the main tobacco alkaloid, nicotine. In addition, anatabine, a minor tobacco alkaloid also present in peppers, tomato, and eggplant presents anti-inflammatory properties in vivo and in vitro. In this study, we aimed to evaluate the anti-inflammatory properties of nicotine and anatabine in a dextran sulfate sodium (DSS) mouse model of UC. Results: Oral administration of anatabine, but not nicotine, reduced the clinical symptoms of DSS-induced colitis. The result of gene expression analysis suggested that anatabine had a restorative effect on global DSS-induced gene expression profiles, while nicotine only had limited effects. Accordingly, MAP findings revealed that anatabine reduced the colonic abundance of DSS-associated cytokines and increased IL-10 abundance. Conclusions: Our results support the amelioration of inflammatory effects by anatabine in the DSS mouse model of UC, and suggest that anatabine constitutes a promising therapeutic agent for IBD treatment. Keywords: Plant-derived alkaloid, Mouse model, Nicotine, Colitis
* Correspondence: [email protected]; [email protected]; [email protected] † Pedro A. Ruiz Castro, Ulrike Kogel, Giuseppe Lo Sasso, Blaine W. Phillips and Alain Sewer contributed equally to this work. 1 Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland 2 Philip Morris International Research Laboratories Pte Ltd, 50 Science Park Road, The Kendall #02-07, Science Park II, Singapore 117406, Singapore
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