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Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain

Metformin is a well-tolerated antidiabetic drug and has recently been repurposed for numerous diseases, including pain. However, a higher dose of metformin is required for effective analgesia, which can potentiate its dose-dependent gastrointestinal side effects. Curcumin is a natural polyphenol and...

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Autores principales: Dasuni Wasana, Peththa Wadu, Hasriadi, Muangnoi, Chawanphat, Vajragupta, Opa, Rojsitthisak, Pranee, Rojsitthisak, Pornchai, Towiwat, Pasarapa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188603/
https://www.ncbi.nlm.nih.gov/pubmed/35690654
http://dx.doi.org/10.1038/s41598-022-13647-7
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author Dasuni Wasana, Peththa Wadu
Hasriadi
Muangnoi, Chawanphat
Vajragupta, Opa
Rojsitthisak, Pranee
Rojsitthisak, Pornchai
Towiwat, Pasarapa
author_facet Dasuni Wasana, Peththa Wadu
Hasriadi
Muangnoi, Chawanphat
Vajragupta, Opa
Rojsitthisak, Pranee
Rojsitthisak, Pornchai
Towiwat, Pasarapa
author_sort Dasuni Wasana, Peththa Wadu
collection PubMed
description Metformin is a well-tolerated antidiabetic drug and has recently been repurposed for numerous diseases, including pain. However, a higher dose of metformin is required for effective analgesia, which can potentiate its dose-dependent gastrointestinal side effects. Curcumin is a natural polyphenol and has beneficial therapeutic effects on pain. Curcumin has been used as an analgesic adjuvant with several analgesic drugs, allowing synergistic antinociceptive effects. Nevertheless, whether curcumin can exert synergistic analgesia with metformin is still unknown. In the present study, the nature of curcumin-metformin anti-inflammatory interaction was evaluated in in vitro using lipopolysaccharide-induced RAW 264.7 macrophage and BV-2 microglia cells. In both macrophage and microglia, curcumin effectively potentiates the anti-inflammatory effects of metformin, indicating potential synergistic effects in both peripheral and central pathways of pain. The nature of the interaction between curcumin and metformin was further recapitulated using a mouse model of formalin-induced pain. Coadministration of curcumin and metformin at a 1:1 fixed ratio of their ED(50) doses significantly reduced the dose required to produce a 50% effect compared to the theoretically required dose in phase II of the formalin test with a combination index value of 0.24. Besides, the synergistic interaction does not appear to involve severe CNS side effects indicated by no motor alterations, no alterations in short-term and long-term locomotive behaviors, and the general well-being of mice. Our findings suggest that curcumin exerts synergistic anti-inflammation with metformin with no potential CNS adverse effects.
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spelling pubmed-91886032022-06-13 Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain Dasuni Wasana, Peththa Wadu Hasriadi Muangnoi, Chawanphat Vajragupta, Opa Rojsitthisak, Pranee Rojsitthisak, Pornchai Towiwat, Pasarapa Sci Rep Article Metformin is a well-tolerated antidiabetic drug and has recently been repurposed for numerous diseases, including pain. However, a higher dose of metformin is required for effective analgesia, which can potentiate its dose-dependent gastrointestinal side effects. Curcumin is a natural polyphenol and has beneficial therapeutic effects on pain. Curcumin has been used as an analgesic adjuvant with several analgesic drugs, allowing synergistic antinociceptive effects. Nevertheless, whether curcumin can exert synergistic analgesia with metformin is still unknown. In the present study, the nature of curcumin-metformin anti-inflammatory interaction was evaluated in in vitro using lipopolysaccharide-induced RAW 264.7 macrophage and BV-2 microglia cells. In both macrophage and microglia, curcumin effectively potentiates the anti-inflammatory effects of metformin, indicating potential synergistic effects in both peripheral and central pathways of pain. The nature of the interaction between curcumin and metformin was further recapitulated using a mouse model of formalin-induced pain. Coadministration of curcumin and metformin at a 1:1 fixed ratio of their ED(50) doses significantly reduced the dose required to produce a 50% effect compared to the theoretically required dose in phase II of the formalin test with a combination index value of 0.24. Besides, the synergistic interaction does not appear to involve severe CNS side effects indicated by no motor alterations, no alterations in short-term and long-term locomotive behaviors, and the general well-being of mice. Our findings suggest that curcumin exerts synergistic anti-inflammation with metformin with no potential CNS adverse effects. Nature Publishing Group UK 2022-06-11 /pmc/articles/PMC9188603/ /pubmed/35690654 http://dx.doi.org/10.1038/s41598-022-13647-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Dasuni Wasana, Peththa Wadu
Hasriadi
Muangnoi, Chawanphat
Vajragupta, Opa
Rojsitthisak, Pranee
Rojsitthisak, Pornchai
Towiwat, Pasarapa
Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain
title Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain
title_full Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain
title_fullStr Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain
title_full_unstemmed Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain
title_short Curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain
title_sort curcumin and metformin synergistically modulate peripheral and central immune mechanisms of pain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188603/
https://www.ncbi.nlm.nih.gov/pubmed/35690654
http://dx.doi.org/10.1038/s41598-022-13647-7
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