Abstract
The relevance and incidence of intestinal bowel diseases (IBD) have been increasing over the last 50 years and the current therapies are characterized by severe side effects, making essential the development of new strategies that combine efficacy and safety in the management of human IBD. Herbal products are highly considered in research aimed at discovering new approaches for IBD therapy and, among others, Cannabis sativa L. has been traditionally used for centuries as an analgesic and anti-inflammatory remedy also in different gastrointestinal disorders. This study aims to investigate the effects of different C. sativa isolated compounds in an in vitro model of intestinal epithelium. The ability of treatments to modulate markers of intestinal dysfunctions was tested on Caco-2 intestinal cell monolayers. Our results, obtained by evaluation of ROS production, TEER and paracellular permeability measurements and tight junctions evaluation show Cannabidiol as the most promising compound against intestinal inflammatory condition. Cannabidiol is able to inhibit ROS production and restore epithelial permeability during inflammatory and oxidative stress conditions, suggesting its possible application as adjuvant in IBD management.
Highlights
The gastrointestinal epithelium forms the body’s larger interface between the external environment providing a functional epithelial barrier that regulates the bi-directional flow of water, ions and macromolecules between the lumen and the host
CBD, THC, cannabidiolic acid (CBDA) and tetrahydrocannabinolic acid (THCA) analytical standards were purchased from Sigma Aldrich
The main cannabinoids identified by comparison with reference standards were CBD, CBDA, THC and THCA (Figure 2)
Summary
The gastrointestinal epithelium forms the body’s larger interface between the external environment providing a functional epithelial barrier that regulates the bi-directional flow of water, ions and macromolecules between the lumen and the host. A breach in the mucosal barrier incites mucosal inflammation leading to a wide array of non-intestinal and intestinal disorders including clinically diagnosed inflammatory bowel disease (IBD). Mucosal permeability (D’Incà et al, 1999; Su et al, 2009) and initial clinical observation indicate that intestinal epithelium of IBD patients is more permeable to paracellular-permeable traces molecules (Hering, et al, 2012). These findings, confirmed in mouse models, support a correlation between the mucosal leakiness and mucosal inflammatory conditions, suggesting that deregulation of intestinal barrier functions by dietary, microbial and immunological factors might precede the clinical IBD manifestation. The intestinal barrier is furnished with immune and non-immune molecules, including mucosal immunoglobulins that contributed to the maintenance of gut homeostasis (Odenwald and Turner 2017)
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