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MECHANISM OF ANALGESIC ACTION OF MANGIFERIN

Grant number: 12/04188-1
Support Opportunities:Scholarships in Brazil - Doctorate
Start date: August 01, 2012
End date: September 30, 2014
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Carlos Amilcar Parada
Grantee:Lilian Wünsch Rocha
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Mangiferin is a major component of M. Indica (Mango) has shown antioxidant and neuroprotective effect in a model of glial and neuronal damage. Studies suggest that mangiferin is able to limit the formation of free radicals to and production of prostaglandins (PGs) by reducing the synthesis of COX-2 in microglia cells. Also, mangiferin inhibits the chemotactic activity of neutrophil-mediated intracellular adhesion molecule 1 (ICAM-1), suggesting their possible anti-inflammatory effect is wider than a possible reduction in prostaglandin synthesis. The sensitization of nociceptors by prostaglandins is an important factor for the onset of inflammatory hyperalgesia, which act directly on nociceptors. Numerous stimuli are able to induce the release of PGs, including interleukin-1 ² (IL-1 ²) that is released at the site of inflammation, or acting as a neuromodulatory molecule in the central nervous system. The model of inflammatory hyperalgesia induced by carrageenan has become popular for inducing the synthesis and release of endogenous prostaglandins thus approaching a model of inflammatory hyperalgesia sensitive to the action of NSAIDs, such as those that normally occur in humans. In this process, carrageenan also induces the migration of neutrophils stimulated by the release of TNF a and especially by the chemokine IL-8. From the pharmacological point of view, the modulation of inflammatory hyperalgesia in peripheral tissue may occur, at least two mechanisms: inhibition of prostaglandin synthesis and stimulation of the L-Arginine - NO - cGMP - PKG - KATP in the fiber nociceptive. Although some literature data suggest that mangiferin has an inhibitory effect on prostaglandin synthesis and neutrophil migration, the scarcity of data can not yet say that this molecule has an anti-hyperalgesic, nor what mechanisms of action are involved. Thus, the objective of this study is to verify that mangiferin has analgesic action in peripheral tissue and elucidate the mechanisms involved in this effect.

News published in Agência FAPESP Newsletter about the scholarship:
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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ROCHA, LILIAN WUNSCH; MAGAYEWSKI BONET, IVAN JOSE; TAMBELI, CLAUDIA HERRERA; DE-FARIA, FELIPE MEIRA; PARADA, CARLOS AMILCAR. Local administration of mangiferin prevents experimental inflammatory mechanical hyperalgesia through CINC-1/epinephrine/PKA pathway and TNF-alpha inhibition. European Journal of Pharmacology, v. 830, p. 87-94, . (12/04188-1)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
ROCHA, Lilian Wünsch. Analgesic mechanism of action of mangiferin. 2015. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.