Repurposing of the Nootropic Drug Vinpocetine as an Analgesic and Anti-Inflammatory Agent: Evidence in a Mouse Model of Superoxide Anion-Triggered Inflammation

Clinically active drugs for the treatment of acute pain have their prescription limited due to the significant side effects they induce. An increase in reactive oxygen species (ROS) has been linked to several conditions, including inflammation and pain processing. Therefore, new or repurposed drugs...

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Main Authors: Yuri Lourenco-Gonzalez, Victor Fattori, Talita P. Domiciano, Ana C. Rossaneis, Sergio M. Borghi, Tiago H. Zaninelli, Catia C. F. Bernardy, Jose C. Alves-Filho, Thiago M. Cunha, Fernando Q. Cunha, Rubia Casagrande, Waldiceu A. Verri
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2019/6481812
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author Yuri Lourenco-Gonzalez
Victor Fattori
Talita P. Domiciano
Ana C. Rossaneis
Sergio M. Borghi
Tiago H. Zaninelli
Catia C. F. Bernardy
Jose C. Alves-Filho
Thiago M. Cunha
Fernando Q. Cunha
Rubia Casagrande
Waldiceu A. Verri
author_facet Yuri Lourenco-Gonzalez
Victor Fattori
Talita P. Domiciano
Ana C. Rossaneis
Sergio M. Borghi
Tiago H. Zaninelli
Catia C. F. Bernardy
Jose C. Alves-Filho
Thiago M. Cunha
Fernando Q. Cunha
Rubia Casagrande
Waldiceu A. Verri
author_sort Yuri Lourenco-Gonzalez
collection DOAJ
description Clinically active drugs for the treatment of acute pain have their prescription limited due to the significant side effects they induce. An increase in reactive oxygen species (ROS) has been linked to several conditions, including inflammation and pain processing. Therefore, new or repurposed drugs with the ability of reducing ROS-triggered responses are promising candidates for analgesic drugs. Vinpocetine is a clinically used nootropic drug with antioxidant, anti-inflammatory, and analgesic properties. However, the effects of vinpocetine have not been investigated in a model with a direct relationship between ROS, inflammation, and pain. Based on that, we aimed to investigate the effects of vinpocetine in a model of superoxide anion-induced pain and inflammation using potassium superoxide (KO2) as a superoxide anion donor to trigger inflammation and pain. In the KO2 model, vinpocetine dose-dependently reduced pain-like behaviors (spontaneous pain and hyperalgesia), paw edema, and neutrophil and mononuclear cell recruitment to the paw skin (assessed by H&E staining, fluorescence, and enzymatic assays) and to the peritoneal cavity. Vinpocetine also restored tissue endogenous antioxidant ability and Nrf2 and Ho-1 mRNA expression and reduced superoxide anion production and gp91phox mRNA expression. We also observed the inhibition of IκBα degradation by vinpocetine, which demonstrates a reduction in the activation of NF-κB explaining the diminished production of IL-33, IL-1β, and TNF-α. Collectively, our data show that vinpocetine alleviates pain and inflammation induced by KO2, which is a mouse model with a direct role of ROS in triggering pain and other inflammatory phenomena. Thus, the results suggest the repurposing of vinpocetine as an anti-inflammatory and analgesic drug.
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spelling doaj-art-ecec4d5a651847f292ee27dcac5acf292025-02-03T05:50:59ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/64818126481812Repurposing of the Nootropic Drug Vinpocetine as an Analgesic and Anti-Inflammatory Agent: Evidence in a Mouse Model of Superoxide Anion-Triggered InflammationYuri Lourenco-Gonzalez0Victor Fattori1Talita P. Domiciano2Ana C. Rossaneis3Sergio M. Borghi4Tiago H. Zaninelli5Catia C. F. Bernardy6Jose C. Alves-Filho7Thiago M. Cunha8Fernando Q. Cunha9Rubia Casagrande10Waldiceu A. Verri11Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid km 480 PR 445, Londrina, Paraná, BrazilDepartamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid km 480 PR 445, Londrina, Paraná, BrazilDepartamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, BrazilDepartamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid km 480 PR 445, Londrina, Paraná, BrazilDepartamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid km 480 PR 445, Londrina, Paraná, BrazilDepartamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid km 480 PR 445, Londrina, Paraná, BrazilDepartmento de Enfermagem, Centro de Ciências da Saúde, Universidade Estadual de Londrina, Av. Robert Koch 60, Londrina, PR, BrazilDepartamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, BrazilDepartamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, BrazilDepartamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, BrazilDepartamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, Av. Robert Koch 60, Londrina, Paraná, BrazilDepartamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid km 480 PR 445, Londrina, Paraná, BrazilClinically active drugs for the treatment of acute pain have their prescription limited due to the significant side effects they induce. An increase in reactive oxygen species (ROS) has been linked to several conditions, including inflammation and pain processing. Therefore, new or repurposed drugs with the ability of reducing ROS-triggered responses are promising candidates for analgesic drugs. Vinpocetine is a clinically used nootropic drug with antioxidant, anti-inflammatory, and analgesic properties. However, the effects of vinpocetine have not been investigated in a model with a direct relationship between ROS, inflammation, and pain. Based on that, we aimed to investigate the effects of vinpocetine in a model of superoxide anion-induced pain and inflammation using potassium superoxide (KO2) as a superoxide anion donor to trigger inflammation and pain. In the KO2 model, vinpocetine dose-dependently reduced pain-like behaviors (spontaneous pain and hyperalgesia), paw edema, and neutrophil and mononuclear cell recruitment to the paw skin (assessed by H&E staining, fluorescence, and enzymatic assays) and to the peritoneal cavity. Vinpocetine also restored tissue endogenous antioxidant ability and Nrf2 and Ho-1 mRNA expression and reduced superoxide anion production and gp91phox mRNA expression. We also observed the inhibition of IκBα degradation by vinpocetine, which demonstrates a reduction in the activation of NF-κB explaining the diminished production of IL-33, IL-1β, and TNF-α. Collectively, our data show that vinpocetine alleviates pain and inflammation induced by KO2, which is a mouse model with a direct role of ROS in triggering pain and other inflammatory phenomena. Thus, the results suggest the repurposing of vinpocetine as an anti-inflammatory and analgesic drug.http://dx.doi.org/10.1155/2019/6481812
spellingShingle Yuri Lourenco-Gonzalez
Victor Fattori
Talita P. Domiciano
Ana C. Rossaneis
Sergio M. Borghi
Tiago H. Zaninelli
Catia C. F. Bernardy
Jose C. Alves-Filho
Thiago M. Cunha
Fernando Q. Cunha
Rubia Casagrande
Waldiceu A. Verri
Repurposing of the Nootropic Drug Vinpocetine as an Analgesic and Anti-Inflammatory Agent: Evidence in a Mouse Model of Superoxide Anion-Triggered Inflammation
Mediators of Inflammation
title Repurposing of the Nootropic Drug Vinpocetine as an Analgesic and Anti-Inflammatory Agent: Evidence in a Mouse Model of Superoxide Anion-Triggered Inflammation
title_full Repurposing of the Nootropic Drug Vinpocetine as an Analgesic and Anti-Inflammatory Agent: Evidence in a Mouse Model of Superoxide Anion-Triggered Inflammation
title_fullStr Repurposing of the Nootropic Drug Vinpocetine as an Analgesic and Anti-Inflammatory Agent: Evidence in a Mouse Model of Superoxide Anion-Triggered Inflammation
title_full_unstemmed Repurposing of the Nootropic Drug Vinpocetine as an Analgesic and Anti-Inflammatory Agent: Evidence in a Mouse Model of Superoxide Anion-Triggered Inflammation
title_short Repurposing of the Nootropic Drug Vinpocetine as an Analgesic and Anti-Inflammatory Agent: Evidence in a Mouse Model of Superoxide Anion-Triggered Inflammation
title_sort repurposing of the nootropic drug vinpocetine as an analgesic and anti inflammatory agent evidence in a mouse model of superoxide anion triggered inflammation
url http://dx.doi.org/10.1155/2019/6481812
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