A numerical and experimental study of the jet buckling phenonenon

Fundação para a Ciência e a Tecnologia (FCT) - POCI 2010 e programas plurianuaisAgências de Financiamento Brazileiras CNP

Preventive Oral Treatment with Resveratrol Pro-prodrugs Drastically Reduce Colon Inflammation in Rodents

12 páginas, 7 figuras, 2 esquemas.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 work was supported by the projects 200670F0131 (CSIC), CICYT-BFU2007-60576, and CSD2007-00063 (Fun-C-Food; Consolider Ingenio 2010). M.L. and R.L. are holders of a JAE-DOC grant from CSIC and M.V.S of a “Ramón y Cajal” grant from MCINN. J.T.C. is holder of a predoctoral grant from MCINN.Peer reviewe