TY - JOUR
T1 - Naringenin inhibits superoxide anion-induced inflammatory pain
T2 - Role of oxidative stress, cytokines, Nrf-2 and the no-cGMP-PKG-KATP channel signaling pathway
AU - Manchope, Marília F.
AU - Calixto-Campos, Cássia
AU - Coelho-Silva, Letícia
AU - Zarpelon, Ana C.
AU - Pinho-Ribeiro, Felipe A.
AU - Georgetti, Sandra R.
AU - Baracat, Marcela M.
AU - Casagrande, Rúbia
AU - Verri, Waldiceu A.
N1 - Funding Information:
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Ministério da Ciências Tecnologia e Inovação (MCTI), Secretaria da Ciência, Tecnologia e Ensino Superior (SETI), Fundação Araucária and Parana State Government grants supported this study (Brazil). A.C.Z. received a postdoctoral fellowship from Fundação Araucária/CAPES (Brazil).
Publisher Copyright:
© 2016 Manchope et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/4
Y1 - 2016/4
N2 - In the present study, the effect and mechanism of action of the flavonoid naringenin were evaluated in superoxide anion donor (KO2)-induced inflammatory pain in mice. Naringenin reduced KO2-induced overt-pain like behavior, mechanical hyperalgesia, and thermal hyperalgesia. The analgesic effect of naringenin depended on the activation of the NO-cGMP-PKG-ATP-sensitive potassium channel (KATP) signaling pathway. Naringenin also reduced KO2-induced neutrophil recruitment (myeloperoxidase activity), tissue oxidative stress, and cytokine production. Furthermore, naringenin downregulated KO2-induced mRNA expression of gp91phox, cyclooxygenase (COX)-2, and preproendothelin-1. Besides, naringenin upregulated KO2-reduced nuclear factor (erythroid-derived 2)-like 2 (Nrf2) mRNA expression coupled with enhanced heme oxygenase (HO-1) mRNA expression. In conclusion, the present study demonstrates that the use of naringenin represents a potential therapeutic approach reducing superoxide anion-driven inflammatory pain. The antinociceptive, antiinflammatory and antioxidant effects are mediated via activation of the NO-cGMP-PKG-KATPchannel signaling involving the induction of Nrf2/HO-1 pathway.
AB - In the present study, the effect and mechanism of action of the flavonoid naringenin were evaluated in superoxide anion donor (KO2)-induced inflammatory pain in mice. Naringenin reduced KO2-induced overt-pain like behavior, mechanical hyperalgesia, and thermal hyperalgesia. The analgesic effect of naringenin depended on the activation of the NO-cGMP-PKG-ATP-sensitive potassium channel (KATP) signaling pathway. Naringenin also reduced KO2-induced neutrophil recruitment (myeloperoxidase activity), tissue oxidative stress, and cytokine production. Furthermore, naringenin downregulated KO2-induced mRNA expression of gp91phox, cyclooxygenase (COX)-2, and preproendothelin-1. Besides, naringenin upregulated KO2-reduced nuclear factor (erythroid-derived 2)-like 2 (Nrf2) mRNA expression coupled with enhanced heme oxygenase (HO-1) mRNA expression. In conclusion, the present study demonstrates that the use of naringenin represents a potential therapeutic approach reducing superoxide anion-driven inflammatory pain. The antinociceptive, antiinflammatory and antioxidant effects are mediated via activation of the NO-cGMP-PKG-KATPchannel signaling involving the induction of Nrf2/HO-1 pathway.
UR - https://www.scopus.com/pages/publications/84963636088
U2 - 10.1371/journal.pone.0153015
DO - 10.1371/journal.pone.0153015
M3 - Article
C2 - 27045367
AN - SCOPUS:84963636088
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 4
M1 - e0153015
ER -