Local administration of mangiferin prevents experimental inflammatory mechanical hyperalgesia through CINC-1/epinephrine/PKA pathway and TNF-alpha inhibition

Author(s)

Rocha, Lilian Wunsch ^[1] ; Magayewski Bonet, Ivan Jose ^[1] ; Tambeli, Claudia Herrera ^[1] ; de-Faria, Felipe Meira ^[1] ; Parada, Carlos Amilcar ^[1]

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Struct & Funct Biol, BR-13083862 Campinas, SP - Brazil

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 830, p. 87-94, JUL 5 2018.
• Web of Science Citations: 5

Abstract

Steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to control inflammatory pain, but there is a risk of gastrointestinal bleeding and increased heart failure risk. The search for new drugs remains ongoing, and natural products are a source for potential new compounds. Mangiferin, a natural xanthone Cglucoside, has demonstrated biological activity, including anti-inflammatory and analgesic properties, but ifs mechanisms are poorly understood. In this study, we investigated the mechanisms underlying the anti-inflammatory and analgesic effects of local administration of mangiferin. We employed an electronic von Frey apparatus to evaluate mechanical hyperalgesia induced by carrageenan in rats. Mangiferin (150-1200 mu g/paw), administered locally into the hindpaw, prevented hyperalgesia in a dose-dependent -150 mu g ( - 9%), 300 mu g ( - 27%, P < 0.01), 600 mu g ( - 77%, P < 0.001) and 1000 mu g ( - 93%, P < 0.001) - and local manner. Mangiferin showed decreased levels of TNF-alpha (P < 0.001) and CINC-1 (P < 0.001), but not IL-1 beta; it also prevented neutrophil migration (P < 0.01), but not the increased COX-2 expression in peripheral tissue challenged with carrageenan. To further explore the mechanisms of mangiferin actions, rats were injected with modulators of inflammation and nociception; mangiferin prevented hyperalgesia induced by IL-1 beta (P < 0.01), CINC-1 (P < 0.01), epinephrine (P < 0.01), 8-Br-cAMP (P < 0.01) or capsaicin (P < 0.01), but not that induced by PGE(2) or alpha,beta-MeATP. Our study shows that mangiferin has anti-inflammatory and analgesic properties when locally administrated. The control of the inflammatory response and mechanical hyperalgesia by mangiferin depends on the inhibition of TNF-alpha production/release and the CINC1/epinephrine/PKA pathway, supporting its marked inhibition of inflammatory mechanical hyperalgesia. (AU)

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