alexa Preventive oral treatment with resveratrol pro-prodrugs drastically reduce colon inflammation in rodents.


Journal of Antivirals & Antiretrovirals

Author(s): Larrosa M, TomCarneiro J, YezGascn MJ, Alcntara D, Selma MV,

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Abstract There is no pharmaceutical or definitive surgical cure for inflammatory bowel diseases (IBDs). The naturally occurring polyphenol resveratrol exerts anti-inflammatory properties. However, its rapid metabolism diminishes its effectiveness in the colon. The design of prodrugs to targeting active molecules to the colon provides an opportunity for therapy of IBDs. Herein we explore the efficacy of different resveratrol prodrugs and pro-prodrugs to ameliorate colon inflammation in the murine dextran sulfate sodium (DSS) model. Mice fed with a very low dose (equivalent to 10 mg for a 70 kg-person) of either resveratrol-3-O-(6'-O-butanoyl)-β-D-glucopyranoside (6) or resveratrol-3-O-(6'-O-octanoyl)-β-D-glucopyranoside (7) did not develop colitis symptoms and improved 6-fold the disease activity index (DAI) compared to resveratrol. Our results indicate that these pro-prodrugs exerted a dual effect: (1) they prevented the rapid metabolism of resveratrol and delivered higher quantities of resveratrol to the colon and (2) they reduced mucosal barrier imbalance and prevented diarrhea, which consequently facilitated the action of the delivered resveratrol in the colon mucosa. This article was published in J Med Chem and referenced in Journal of Antivirals & Antiretrovirals

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