Abstract
Ulcerative colitis (UC), one of the two main types of inflammatory bowel disease, has no effective treatment. Rosmarinic acid (RA) is a polyphenol that, when administered orally, is metabolised in the small intestine, compromising its beneficial effects. We used chitosan/nutriose-coated niosomes loaded with RA to protect RA from gastric degradation and target the colon and evaluated their effect on acute colitis induced by 4% dextran sodium sulphate (DSS) for seven days in mice. RA-loaded nanovesicles (5, 10 and 20 mg/kg) or free RA (20 mg/kg) were orally administered from three days prior to colitis induction and during days 1, 3, 5 and 7 of DSS administration. RA-loaded nanovesicles improved body weight loss and disease activity index as well as increased mucus production and decreased myeloperoxidase activity and TNF-α production. Moreover, RA-loaded nanovesicles downregulated protein expression of inflammasome components such as NLR family pyrin domain-containing 3 (NLRP3), adaptor protein (ASC) and caspase-1, and the consequent reduction of IL-1β levels. Furthermore, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expression increased after the RA-loaded nanovesicles treatment However, these mechanistic changes were not detected with the RA-free treatment. Our findings suggest that the use of chitosan/nutriose-coated niosomes to increase RA local bioavailability could be a promising nutraceutical strategy for oral colon-targeted UC therapy.
Highlights
Inflammatory bowel disease (IBD), comprising Ulcerative colitis (UC) and Crohn’s disease (CD), is characterised by chronic and relapsing intestinal inflammation
260.7, 429.7 and 480.5 nm for uncoated niosomes loaded with Rosmarinic acid (RA), empty chitosan and nutriose-coated niosomes and chitosan and nutriose-coated niosomes loaded with RA, respectively
To further explore the protective mechanism of RA-loaded nanovesicles, we investigated their ability to activate nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which stimulates the transcription of antioxidant genes and detoxification of enzymes such as heme oxygenase-1 (HO-1) to protect against dextran sodium sulphate (DSS)-induced oxidative damage [5]
Summary
Inflammatory bowel disease (IBD), comprising UC and Crohn’s disease (CD), is characterised by chronic and relapsing intestinal inflammation. The etiology of IBD is still unclear, an aberrant innate immune response against internal and external threatening factors has been suggested to have a crucial role in IBD pathogenesis [1]. Inflammasome is a cytosolic multiprotein complex involved in the innate immune response, which is stimulated by many types of tissue damage. NLRP3 is one of the best representative inflammasomes, which has been associated with UC pathogenesis [2,3]. Mature IL-1β is a key inflammatory mediator that participates in the inflammation occurring in IBD patients, and its overproduction is related to augmented disease severity [4]
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