Anatabine ameliorates intestinal inflammation and reduces the production of pro-inflammatory factors in a dextran sulfate sodium mouse model of colitis

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.

Development of an Advanced Multicellular Intestinal Model for Assessing Immunomodulatory Properties of Anti-Inflammatory Compounds

“…On the other hand, the administration route of nicotine in vivo models (i.e., oral administration, subcutaneous injection) plays a crucial role in the potential antiinflammatory effects of nicotine in intestinal inflammation (AlSharari et al, 2013) therefore we might have not been able to capture the full potential of nicotine with our model as nicotine dissemination through the blood stream, intestinal absorption, or gastrointestinal metabolism might play a crucial role in nicotine bioavailability and anti-inflammatory effects in the gut. Of note, other minor tobacco alkaloids, nAChR agonists as well, were also suggested as having potential antiinflammatory effects (Olsson et al, 1993;Bai et al, 2007;Alijevic et al, 2020;Ruiz Castro et al, 2020). Among these, the alkaloids anatabine and cotinine have displayed protective effects in animal models of inflammatory conditions, including Alzheimer's disease (Paris et al, 2011), Parkinson's disease (Barreto et al, 2014), sepsis (Zabrodskii et al, 2015), and IBD (Bai et al, 2007;Ruiz Castro et al, 2020).…”

“…Of note, other minor tobacco alkaloids, nAChR agonists as well, were also suggested as having potential antiinflammatory effects (Olsson et al, 1993;Bai et al, 2007;Alijevic et al, 2020;Ruiz Castro et al, 2020). Among these, the alkaloids anatabine and cotinine have displayed protective effects in animal models of inflammatory conditions, including Alzheimer's disease (Paris et al, 2011), Parkinson's disease (Barreto et al, 2014), sepsis (Zabrodskii et al, 2015), and IBD (Bai et al, 2007;Ruiz Castro et al, 2020). Our results on anatabine are thus substantiated by the findings of previous studies that have demonstrated the anti-inflammatory effects of anatabine in in vivo disease models, indicating that this pyridine alkaloid might be a potential candidate for development of anti-inflammatory therapies (Paris et al, 2011;Paris et al, 2013b).…”

“…These natural derived bioactive compounds can be sourced from living organisms, such as bacteria, fungi, plants, and animals (Moreira et al, 2018). Plant-derived alkaloids have been shown to possess anti-inflammatory properties as demonstrated in animal models of disease, including inflammatory bowel disease (IBD), a group of disorders characterized by chronic inflammation of the gastrointestinal tract (Niu et al, 2013;Chen et al, 2017;Ruiz Castro et al, 2020). The positive effects of alkaloid have been linked to a modulation of intestinal oxidative stress (Karatay et al, 2017;Rodrigues de Carvalho et al, 2018), a strengthening of the epithelial barrier function (Zhang et al, 2017), and a boost of gut microbiota (Zhang et al, 2018).…”

Engineering Metabolism in Nicotiana Species: A Promising Future

“…Nicotine and all minor tobacco alkaloids have been shown to be pharmacologically active upon binding to several nicotinic acetylcholine receptors (nAChRs). Nicotine, anatabine, anabasine, anabaseine, and cotinine display protective effects in animal models of several inflammatory conditions, including sepsis, Parkinson's disease, Alzheimer's disease, and IBD [14]. Due to their amenability to both nuclear and plastid transformation, some Nicotiana species have been extensively used for metabolic engineering efforts based on classical transgenesis.…”

Anatabine, Nornicotine, and Anabasine Reduce Weight Gain and Body Fat through Decreases in Food Intake and Increases in Physical Activity

“…Minor tobacco alkaloids are naturally occurring compounds [5] that are structurally [6] and functionally [7][8][9] analogous to nicotine, the primary psychoactive component in cigarettes, and have been the subject of research on novel therapeutics for smoking cessation [10], cognitive disorders including Alzheimer's disease [11][12][13] and Parkinson's disease [14], traumatic brain injury [15], inflammatory bowel disease [16] and psoriasis (Rock Creek Pharmaceuticals), as well as a novel strategy for pain management [17]. Previous research investigating the role of nicotine on body weight has repeatedly demonstrated that cigarette smoking and/or nicotine administration produces sustained weight loss and reduced food intake [18][19][20][21][22].…”