Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8529051 | European Journal of Pharmacology | 2018 | 25 Pages |
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 C-glucoside, has demonstrated biological activity, including anti-inflammatory and analgesic properties, but it's 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 (150-1200â¯Âµg/paw), administered locally into the hindpaw, prevented hyperalgesia in a dose-dependent - 150â¯Âµg (â 9%), 300â¯Âµg (â 27%, Pâ¯<â¯0.01), 600â¯Âµg (â 77%, Pâ¯<â¯0.001) and 1000â¯Âµg (â 93%, Pâ¯<â¯0.001) - and local manner. Mangiferin showed decreased levels of TNF-α (Pâ¯<â¯0.001) and CINC-1 (Pâ¯<â¯0.001), but not IL-1β; it also prevented neutrophil migration (Pâ¯<â¯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-1β (Pâ¯<â¯0.01), CINC-1 (Pâ¯<â¯0.01), epinephrine (Pâ¯<â¯0.01), 8-Br-cAMP (Pâ¯<â¯0.01) or capsaicin (Pâ¯<â¯0.01), but not that induced by PGE2 or α,β-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-α production/release and the CINC1/epinephrine/PKA pathway, supporting its marked inhibition of inflammatory mechanical hyperalgesia.
Related Topics
Life Sciences
Neuroscience
Cellular and Molecular Neuroscience
Authors
Lilian Wünsch Rocha, Ivan José Magayewski Bonet, Claudia Herrera Tambeli, Felipe Meira de-Faria, Carlos Amilcar Parada,