Analgesic mechanism of action of mangiferin

Author(s)

Lilian Wünsch Rocha

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2015-04-29

Examining board members

Carlos Amílcar Parada; Maria Martha Campos; Clélia Akiko Hiruma Lima; César Renato Sartori; Jozi Godoy Figueiredo

• Advisor: Carlos Amílcar Parada

Abstract

Vimang® is an herbal medicine constituted by the aqueous extract of Mangifera indica L plant. It is used in Cuba for the treatment of stress and immunopathological diseases because it has recognized antioxidant properties. The major component of this extract is mangiferin (about 7%) and literature data indicates that both, extract and mangiferin, have antinociceptive activity. The aim of this study was to evaluate the antihyperalgesic potential of mangiferin in peripheral tissue and investigate its possible mechanism of action in rats. Were used inflammatory hyperalgesia models such as carrageenan-induced hyperalgesia (100 ?g/paw), epinephrine (1 ?g/paw) and the inflammatory mediators PGE2 (100 ng/paw), IL-1? (0.5 pg/ paw) and CINC-1 (1 pg/paw). Hyperalgesia was also induced by ?,?-meATP (P2X3 receptor agonist) (50 ?g/paw) and 8-Br-cAMP (PKA activator) (0.01 ?g/paw). The evaluation of mechanical hyperalgesia was performed using Electronic Von Frey. The acute model of nociception induced by capsaicin (0.5 ?g/paw) was also performed. In addition to the behavioral experiments, the dosage of pro-inflammatory cytokines IL-1?, TNF-? and CINC-1 was performed, evaluation of the migration of neutrophils through the myeloperoxidase dosage, Western Blotting for COX-1 and COX-2, and the calcium imaging test to check possible interference of mangiferin in purinergic receptors. In all molecular tests, inflammation was induced by carrageenan and the plantar tissue of the hind paw of the rats was collected 3 hours after intraplantar injection. In all experiments in which there was pretreatment with mangiferin, it was conducted by local administration, intraplantar. To verify the involvement of the purinergic receptors in the mangiferin mechanism of action, using calcium imaging test, in vitro calcium influx was induced by ?, ?-meATP. The results demonstrate that mangiferin at doses of 300, 600 and 1200 ?g/paw reduced carrageenan-induced hyperalgesia in a dose-dependent manner and without providing systemic effect, which was evaluated through the threshold of the contralateral paw. For other experiments the submaximal dose of 600 ?g/paw was used. Mechanical hyperalgesia induced by epinephrine, IL-1? and CINC-1, but not by PGE2, was prevented by local administration of mangiferin. It was also observed mangiferin effect of reducing the capsaicin-induced nociception. In the ELISA test, the mangiferin pretreatment reduced the local concentration of the cytokine TNF-? and chemokine CINC-1, however, IL-1? levels were unchanged. The neutrophil migration was also assessed and local treatment with mangiferin reduced neutrophil migration induced by carrageenan into the plantar tissue. The results obtained with the COX-1 and COX-2 proteins dosage by Western Blotting demonstrated that local treatment with mangiferin did not alter the expression of these proteins. In vitro evaluation of the activity of mangiferin in inhibiting calcium influx induced by ?, ?-meATP there were no positive results, mangiferin did not cause desensitization in neurons. Taken together, the results show that mangiferin has anti-hyperalgesic activity and possibly this action is related to its ability to reduce cytokines that are essential to the development of inflammatory hyperalgesia (AU)

• FAPESP's process: 12/04188-1 - MECHANISM OF ANALGESIC ACTION OF MANGIFERIN
• Grantee: Lilian Wünsch Rocha
• Support Opportunities: Scholarships in Brazil - Doctorate