Quercetin Reduces Antinociceptive but Not the Anti-Inflammatory Effects of Indomethacin, Ketorolac, and Celecoxib in Rats with Gout-like Pain

The objective of this study was to determine the pharmacological interaction of some common NSAIDs in the presence of quercetin (QUER). Indomethacin (IND), ketorolac (KET), or celecoxib (CEL) were assessed alone and in combination with QUER using experimental gout-arthritic pain and the carrageenan-...

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Main Authors: José Aviles-Herrera, Guadalupe Esther Ángeles-López, Myrna Déciga-Campos, María Eva González-Trujano, Gabriel Fernando Moreno-Pérez, Ricardo Reyes-Chilpa, Irma Romero, Amalia Alejo-Martínez, Rosa Ventura-Martínez
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/15/3196
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author José Aviles-Herrera
Guadalupe Esther Ángeles-López
Myrna Déciga-Campos
María Eva González-Trujano
Gabriel Fernando Moreno-Pérez
Ricardo Reyes-Chilpa
Irma Romero
Amalia Alejo-Martínez
Rosa Ventura-Martínez
author_facet José Aviles-Herrera
Guadalupe Esther Ángeles-López
Myrna Déciga-Campos
María Eva González-Trujano
Gabriel Fernando Moreno-Pérez
Ricardo Reyes-Chilpa
Irma Romero
Amalia Alejo-Martínez
Rosa Ventura-Martínez
author_sort José Aviles-Herrera
collection DOAJ
description The objective of this study was to determine the pharmacological interaction of some common NSAIDs in the presence of quercetin (QUER). Indomethacin (IND), ketorolac (KET), or celecoxib (CEL) were assessed alone and in combination with QUER using experimental gout-arthritic pain and the carrageenan-induced edema test in rats to evaluate their antinociceptive and anti-inflammatory effects, respectively. The antinociceptive effect of each NSAID was also analyzed after the repeated administration of QUER for 10 days. Molecular docking analysis on COX-1/COX-2 with each drug was explored to analyze the pharmacological interaction. QUER produced minimal antinociceptive or anti-inflammatory effects on experimental gout-arthritic pain or on the carrageenan-induced edema in rats. Additionally, QUER reduced the antinociceptive effect of NSAIDs, mainly those COX-1 inhibitors (IND and KET), when they were combined. However, QUER did not modify the anti-inflammatory effect of these COX-1 inhibitors and slightly improved the anti-inflammatory effect of the COX-2 inhibitor (CEL). According to the docking analysis, COX-1 and COX-2 are likely implicated in these pharmacological interactions. In conclusion, QUER, a known bioactive natural product, may alter the antinociceptive efficacy of NSAIDs commonly used to relieve gout-like pain and suggests not using them together to prevent a negative therapeutic interaction in this effect.
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spelling doaj-art-fad48ed9e42147c8a9cb4afcf5bd64722025-08-20T03:36:27ZengMDPI AGMolecules1420-30492025-07-013015319610.3390/molecules30153196Quercetin Reduces Antinociceptive but Not the Anti-Inflammatory Effects of Indomethacin, Ketorolac, and Celecoxib in Rats with Gout-like PainJosé Aviles-Herrera0Guadalupe Esther Ángeles-López1Myrna Déciga-Campos2María Eva González-Trujano3Gabriel Fernando Moreno-Pérez4Ricardo Reyes-Chilpa5Irma Romero6Amalia Alejo-Martínez7Rosa Ventura-Martínez8Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, MexicoDepartamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, MexicoSección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional (IPN), Ciudad de México 11340, MexicoLaboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñiz”, Ciudad de México 14370, MexicoLaboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñiz”, Ciudad de México 14370, MexicoInstituto de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, MexicoDepartamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, MexicoLaboratorio 7 de Dolor y Analgesia, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Sede Sur, Ciudad de México 14330, MexicoDepartamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, MexicoThe objective of this study was to determine the pharmacological interaction of some common NSAIDs in the presence of quercetin (QUER). Indomethacin (IND), ketorolac (KET), or celecoxib (CEL) were assessed alone and in combination with QUER using experimental gout-arthritic pain and the carrageenan-induced edema test in rats to evaluate their antinociceptive and anti-inflammatory effects, respectively. The antinociceptive effect of each NSAID was also analyzed after the repeated administration of QUER for 10 days. Molecular docking analysis on COX-1/COX-2 with each drug was explored to analyze the pharmacological interaction. QUER produced minimal antinociceptive or anti-inflammatory effects on experimental gout-arthritic pain or on the carrageenan-induced edema in rats. Additionally, QUER reduced the antinociceptive effect of NSAIDs, mainly those COX-1 inhibitors (IND and KET), when they were combined. However, QUER did not modify the anti-inflammatory effect of these COX-1 inhibitors and slightly improved the anti-inflammatory effect of the COX-2 inhibitor (CEL). According to the docking analysis, COX-1 and COX-2 are likely implicated in these pharmacological interactions. In conclusion, QUER, a known bioactive natural product, may alter the antinociceptive efficacy of NSAIDs commonly used to relieve gout-like pain and suggests not using them together to prevent a negative therapeutic interaction in this effect.https://www.mdpi.com/1420-3049/30/15/3196gout paininfra-additive interactionnatural productsNSAIDsquercetin
spellingShingle José Aviles-Herrera
Guadalupe Esther Ángeles-López
Myrna Déciga-Campos
María Eva González-Trujano
Gabriel Fernando Moreno-Pérez
Ricardo Reyes-Chilpa
Irma Romero
Amalia Alejo-Martínez
Rosa Ventura-Martínez
Quercetin Reduces Antinociceptive but Not the Anti-Inflammatory Effects of Indomethacin, Ketorolac, and Celecoxib in Rats with Gout-like Pain
Molecules
gout pain
infra-additive interaction
natural products
NSAIDs
quercetin
title Quercetin Reduces Antinociceptive but Not the Anti-Inflammatory Effects of Indomethacin, Ketorolac, and Celecoxib in Rats with Gout-like Pain
title_full Quercetin Reduces Antinociceptive but Not the Anti-Inflammatory Effects of Indomethacin, Ketorolac, and Celecoxib in Rats with Gout-like Pain
title_fullStr Quercetin Reduces Antinociceptive but Not the Anti-Inflammatory Effects of Indomethacin, Ketorolac, and Celecoxib in Rats with Gout-like Pain
title_full_unstemmed Quercetin Reduces Antinociceptive but Not the Anti-Inflammatory Effects of Indomethacin, Ketorolac, and Celecoxib in Rats with Gout-like Pain
title_short Quercetin Reduces Antinociceptive but Not the Anti-Inflammatory Effects of Indomethacin, Ketorolac, and Celecoxib in Rats with Gout-like Pain
title_sort quercetin reduces antinociceptive but not the anti inflammatory effects of indomethacin ketorolac and celecoxib in rats with gout like pain
topic gout pain
infra-additive interaction
natural products
NSAIDs
quercetin
url https://www.mdpi.com/1420-3049/30/15/3196
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