Investigation of molecular and biophysical mechanisms of action involved in the anti-inflammatory intestinal response of 6,7-dihydroxy-4-methylcoumarin

• Grant number: 13/19138-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2014
• End date: February 28, 2017
• Field of knowledge: Health Sciences - Pharmacy - Pharmacognosy
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Luiz Claudio Di Stasi
• Grantee: Alexandre Tanimoto
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Inflammatory Bowel Disease (IBD) shows increasing incidence in the world and are characterized as a relapsing chronic idiopathic inflammatory process of the gastrointestinal tract. Researching new drugs to treat IBD, which remains without cure, must be lead throughout interdisciplinary aspects, especially on the main mediators involved in the anti-inflammatory response of new potential substances to IBD treatment in humans. Recently, our research group demonstrated that 6,7-dihydroxy-4-methylcoumarin (4-ME), a natural coumarin derivative, has a potent anti-inflammatory activity, which was related to the reduction of proinflammatory cytokines and to 4-ME antioxidant activity. Based on the information above, the aims of the present project are to identify the antioxidant mechanisms of action involved in the anti-inflammatory response produced by 4-ME in rat model of TNBS-induced intestinal inflammation and to characterize, by biophysics technics, if exists the direct interaction between 4-ME and the main mediators of oxidative stress present in colonic inflammation, such as glutathione peroxidase (GPx) and the inhibitory protein ºB (IºB). For this, studies will follow into the rat model of TNBS-induced intestinal inflammation by quantification of free radicals; gene expression and also of enzymatic activity of pro/antioxidant enzymes or transcription factors, such as lipoxygenase, ciclooxygenase, mieloperoxydase, superoxide dismutase, catalase, glutathione dependent enzymes, NF-ºB and Nrf2 and, finally to evaluate interaction parameters of 4-ME with GPx and IºB via fluorescent espctroscopy through fluorimetric titration, constant of association calculations and verification of biding sites existing in the proteins for 4-ME. The present work expects to elucidate the main mechanisms of action involved in the anti-inflammatory and antioxidant effects of 4-ME. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

TANIMOTO, Alexandre. Investigation of molecular and biophysical mechanisms of action involved in the anti-inflammatory intestinal response of 6,7-dihydroxy-4-methylcoumarin. 2017. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.