β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo

Abstract Inflammation is a complex biological response involving the immune, autonomic, vascular, and somatosensory systems that occurs through the synthesis of inflammatory mediators and pain induction by the activation of nociceptors. Staphylococcus aureus, the main cause of bacteremia, is one of...

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Main Authors: Laís Ferraz Brito Sousa, Hellen Braga Martins Oliveira, Nathan das Neves Selis, Lorena Lobo Brito Morbeck, Talita Costa Santos, Lucas Santana Coelho da Silva, Jully Chayra Santos Viana, Mariane Mares Reis, Beatriz Almeida Sampaio, Guilherme Barreto Campos, Jorge Timenetsky, Regiane Yatsuda, Lucas Miranda Marques
Format: Article
Language:English
Published: Nature Portfolio 2022-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-23842-1
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author Laís Ferraz Brito Sousa
Hellen Braga Martins Oliveira
Nathan das Neves Selis
Lorena Lobo Brito Morbeck
Talita Costa Santos
Lucas Santana Coelho da Silva
Jully Chayra Santos Viana
Mariane Mares Reis
Beatriz Almeida Sampaio
Guilherme Barreto Campos
Jorge Timenetsky
Regiane Yatsuda
Lucas Miranda Marques
author_facet Laís Ferraz Brito Sousa
Hellen Braga Martins Oliveira
Nathan das Neves Selis
Lorena Lobo Brito Morbeck
Talita Costa Santos
Lucas Santana Coelho da Silva
Jully Chayra Santos Viana
Mariane Mares Reis
Beatriz Almeida Sampaio
Guilherme Barreto Campos
Jorge Timenetsky
Regiane Yatsuda
Lucas Miranda Marques
author_sort Laís Ferraz Brito Sousa
collection DOAJ
description Abstract Inflammation is a complex biological response involving the immune, autonomic, vascular, and somatosensory systems that occurs through the synthesis of inflammatory mediators and pain induction by the activation of nociceptors. Staphylococcus aureus, the main cause of bacteremia, is one of the most common and potent causes of inflammation in public health, with worse clinical outcomes in hospitals. Antioxidant substances have been evaluated as alternative therapeutic analgesics, antioxidants, anti-inflammatory agents, antitumor agents, and bactericides. Among these, we highlight the essential oils of aromatic plants, such as β-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The objective of this study was to evaluate the biological activities of BCP–DHA association in in vitro and in vivo experimental models of antinociception and inflammation. To determine the anti-inflammatory effects, monocytes isolated from the peripheral blood of adult male volunteers were infected with methicillin-resistant S. aureus and incubated with treatment for cytokine dosage and gene expression analysis. Antinociceptive effects were observed in the three models when comparing the control (saline) and the BCP-DHA treatment groups. For this purpose, the antinociceptive effects were evaluated in animal models using the following tests: acetic acid-induced abdominal writhing, paw edema induced by formalin intraplantar injection, and von Frey hypernociception. There was a significant reduction in the GM-CSF, TNFα, IL-1, IL-6, and IL-12 levels and an increase in IL-10 levels in the BCP-DHA treatment groups, in addition to negative regulation of the expression of the genes involved in the intracellular inflammatory signaling cascade (IL-2, IL-6, IRF7, NLRP3, and TYK2) in all groups receiving treatment, regardless of the presence of infection. Statistically significant results (p < 0.05) were obtained in the acetic acid-induced abdominal writhing test, evaluation of paw edema, evaluation of paw flinching and licking in the formalin intraplantar injection model, and the von Frey hypernociception test. Therefore, BCP and DHA, either administered individually or combined, demonstrate potent anti-inflammatory and antinociceptive effects.
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spelling doaj.art-d59d8f00844b49dc94695ecec4ed44c92022-12-22T04:35:37ZengNature PortfolioScientific Reports2045-23222022-11-0112111410.1038/s41598-022-23842-1β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivoLaís Ferraz Brito Sousa0Hellen Braga Martins Oliveira1Nathan das Neves Selis2Lorena Lobo Brito Morbeck3Talita Costa Santos4Lucas Santana Coelho da Silva5Jully Chayra Santos Viana6Mariane Mares Reis7Beatriz Almeida Sampaio8Guilherme Barreto Campos9Jorge Timenetsky10Regiane Yatsuda11Lucas Miranda Marques12Multidisciplinary Institute of Health, Federal University of Bahia (UFBA)University of Santa Cruz (UESC)University of Santa Cruz (UESC)Multidisciplinary Institute of Health, Federal University of Bahia (UFBA)Multidisciplinary Institute of Health, Federal University of Bahia (UFBA)University of Santa Cruz (UESC)Multidisciplinary Institute of Health, Federal University of Bahia (UFBA)Multidisciplinary Institute of Health, Federal University of Bahia (UFBA)Multidisciplinary Institute of Health, Federal University of Bahia (UFBA)Multidisciplinary Institute of Health, Federal University of Bahia (UFBA)Department of Microbiology, Institute of Biomedical Science, University of São PauloMultidisciplinary Institute of Health, Federal University of Bahia (UFBA)Multidisciplinary Institute of Health, Federal University of Bahia (UFBA)Abstract Inflammation is a complex biological response involving the immune, autonomic, vascular, and somatosensory systems that occurs through the synthesis of inflammatory mediators and pain induction by the activation of nociceptors. Staphylococcus aureus, the main cause of bacteremia, is one of the most common and potent causes of inflammation in public health, with worse clinical outcomes in hospitals. Antioxidant substances have been evaluated as alternative therapeutic analgesics, antioxidants, anti-inflammatory agents, antitumor agents, and bactericides. Among these, we highlight the essential oils of aromatic plants, such as β-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The objective of this study was to evaluate the biological activities of BCP–DHA association in in vitro and in vivo experimental models of antinociception and inflammation. To determine the anti-inflammatory effects, monocytes isolated from the peripheral blood of adult male volunteers were infected with methicillin-resistant S. aureus and incubated with treatment for cytokine dosage and gene expression analysis. Antinociceptive effects were observed in the three models when comparing the control (saline) and the BCP-DHA treatment groups. For this purpose, the antinociceptive effects were evaluated in animal models using the following tests: acetic acid-induced abdominal writhing, paw edema induced by formalin intraplantar injection, and von Frey hypernociception. There was a significant reduction in the GM-CSF, TNFα, IL-1, IL-6, and IL-12 levels and an increase in IL-10 levels in the BCP-DHA treatment groups, in addition to negative regulation of the expression of the genes involved in the intracellular inflammatory signaling cascade (IL-2, IL-6, IRF7, NLRP3, and TYK2) in all groups receiving treatment, regardless of the presence of infection. Statistically significant results (p < 0.05) were obtained in the acetic acid-induced abdominal writhing test, evaluation of paw edema, evaluation of paw flinching and licking in the formalin intraplantar injection model, and the von Frey hypernociception test. Therefore, BCP and DHA, either administered individually or combined, demonstrate potent anti-inflammatory and antinociceptive effects.https://doi.org/10.1038/s41598-022-23842-1
spellingShingle Laís Ferraz Brito Sousa
Hellen Braga Martins Oliveira
Nathan das Neves Selis
Lorena Lobo Brito Morbeck
Talita Costa Santos
Lucas Santana Coelho da Silva
Jully Chayra Santos Viana
Mariane Mares Reis
Beatriz Almeida Sampaio
Guilherme Barreto Campos
Jorge Timenetsky
Regiane Yatsuda
Lucas Miranda Marques
β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo
Scientific Reports
title β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo
title_full β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo
title_fullStr β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo
title_full_unstemmed β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo
title_short β-caryophyllene and docosahexaenoic acid, isolated or associated, have potential antinociceptive and anti-inflammatory effects in vitro and in vivo
title_sort β caryophyllene and docosahexaenoic acid isolated or associated have potential antinociceptive and anti inflammatory effects in vitro and in vivo
url https://doi.org/10.1038/s41598-022-23842-1
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