• Kenji W Ruiz-Miyazawa, Felipe A Pinho-Ribeiro, Ana C Zarpelon, Larissa Staurengo-Ferrari, Rangel L Silva, Jose C Alves-Filho, Thiago M Cunha, Fernando Q Cunha, Rubia Casagrande, and Waldiceu A Verri.
• Departamento de Ciências Patológicas, Universidade Estadual de Londrina-UEL, Rod. Celso Garcia Cid, Km 380, PR445, 86057-970, Cx. Postal 10.011, Londrina, Paraná, Brazil.
• Chem. Biol. Interact. 2015 Jul 25; 237: 9-17.

AbstractIn response to lipopolysaccharide (LPS), tissue resident macrophages and recruited neutrophils produce inflammatory mediators through activation of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway. These mediators include inflammatory cytokines and reactive oxygen species that, in turn, sensitize nociceptors and lead to inflammatory pain. Vinpocetine is a nootropic drug widely used to treat cognitive and neurovascular disorders, and more recently its anti-inflammatory properties through inhibition of NF-κB activation have been described. In the present study, we used the intraplantar and intraperitoneal LPS stimulus in mice to investigate the effects of vinpocetine pre-treatment (3, 10, or 30mg/kg by gavage) in hyperalgesia, leukocyte recruitment, oxidative stress, and pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-33). LPS-induced NF-κB activation and cytokine production were investigated using RAW 264.7 macrophage cell in vitro. Vinpocetine (30mg/kg) significantly reduces hyperalgesia to mechanical and thermal stimuli, and myeloperoxidase (MPO) activity (a neutrophil marker) in the plantar paw skin, and also inhibits neutrophil and mononuclear cell recruitment, superoxide anion and nitric oxide production, oxidative stress, and cytokine production (TNF-α, IL-1β and IL-33) in the peritoneal cavity. At least in part, these effects seem to be mediated by direct effects of vinpocetine on macrophages, since it inhibited the production of the same cytokines (TNF-α, IL-1β and IL-33) and the NF-κB activation in LPS-stimulated RAW 264.7 macrophages. Our results suggest that vinpocetine represents an important therapeutic approach to treat inflammation and pain induced by a gram-negative bacterial component by targeting NF-κB activation and NF-κB-related cytokine production in macrophages.Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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