2024-03-29T14:06:56Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/374412021-07-21T12:54:00Zcom_10261_38com_10261_5col_10261_291
2011-07-04T07:19:35Z
urn:hdl:10261/37441
Preventive Oral Treatment with Resveratrol Pro-prodrugs Drastically Reduce Colon Inflammation in Rodents
Larrosa, Mar
Tomé-Carneiro, Joao
Yáñez-Gascón, María J.
Alcántara, David
Selma, María Victoria
Beltrán Riquelme, David
García-Conesa, María Teresa
Urbán, Cristina
Lucas, Ricardo
Tomás Barberán, Francisco
Morales, Juan C.
Espín de Gea, Juan Carlos
Inflamatory bowel diseases (IBDs)
Polyphenol
Anti-inflammatory
Colon
Dextran suflate sodium (DSS)
Resveratrol
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.
2011-07-04T07:19:35Z
2011-07-04T07:19:35Z
2010-09-24
artículo
Journal of Medicinal of Chemistry 53(20): 7365-7376 (2010)
0022-2623
20866032
http://hdl.handle.net/10261/37441
10.1021/jm1007006
eng
http://dx.doi.org/10.1021/jm1007006
closedAccess
American Chemical Society