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The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice

Inflammation is an organism’s biological defense mechanism. Acute and chronic inflammation of the body triggers the production of pro- and anti-inflammatory pathways that can affect the content of cytokines in the brain and thus cause brain inflammation. Disorders such as depression and posttraumati...

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Autores principales: Zanikov, Timur, Gerasymchuk, Marta, Ghasemi Gojani, Esmaeel, Robinson, Gregory Ian, Asghari, Shima, Groves, Alyssa, Haselhorst, Lucie, Nandakumar, Sanjana, Stahl, Cora, Cameron, Mackenzie, Li, Dongping, Rodriguez-Juarez, Rocio, Snelling, Alexandra, Hudson, Darryl, Fiselier, Anna, Kovalchuk, Olga, Kovalchuk, Igor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10056123/
https://www.ncbi.nlm.nih.gov/pubmed/36985596
http://dx.doi.org/10.3390/molecules28062624
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author Zanikov, Timur
Gerasymchuk, Marta
Ghasemi Gojani, Esmaeel
Robinson, Gregory Ian
Asghari, Shima
Groves, Alyssa
Haselhorst, Lucie
Nandakumar, Sanjana
Stahl, Cora
Cameron, Mackenzie
Li, Dongping
Rodriguez-Juarez, Rocio
Snelling, Alexandra
Hudson, Darryl
Fiselier, Anna
Kovalchuk, Olga
Kovalchuk, Igor
author_facet Zanikov, Timur
Gerasymchuk, Marta
Ghasemi Gojani, Esmaeel
Robinson, Gregory Ian
Asghari, Shima
Groves, Alyssa
Haselhorst, Lucie
Nandakumar, Sanjana
Stahl, Cora
Cameron, Mackenzie
Li, Dongping
Rodriguez-Juarez, Rocio
Snelling, Alexandra
Hudson, Darryl
Fiselier, Anna
Kovalchuk, Olga
Kovalchuk, Igor
author_sort Zanikov, Timur
collection PubMed
description Inflammation is an organism’s biological defense mechanism. Acute and chronic inflammation of the body triggers the production of pro- and anti-inflammatory pathways that can affect the content of cytokines in the brain and thus cause brain inflammation. Disorders such as depression and posttraumatic stress disorder (PTSD) are often associated with elevated inflammation. Recently, positive and promising clinical results of psilocybin for the treatment of depression and PTSD were reported. Thus, we decided to test whether psilocybin alone or in combination with eugenol, an anti-inflammatory and antioxidant agent, would prevent the increase in or decrease the content of cytokines in the brain of C57BL/6J mice injected with lipopolysaccharides (LPS). Two experiments were performed, one with pre-treatment of mice through gavage with psilocybin (0.88 mg/kg), eugenol (17.6 mg/kg), or combinations of psilocybin and eugenol (1:10, 1:20, or 1:50), followed by intraperitoneal injection of LPS, and the second, post-treatment, with initial injection with LPS, followed by treatment with psilocybin, eugenol, or their combination. Brain tissues were collected, and cytokines were analyzed by qRT-PCR, Western blot, and ELISA. Data were analyzed with a one-way ANOVA followed by Tukey’s post hoc test or with multiple unpaired t-tests. LPS upregulated mRNA expression of COX-2, TNF-α, IL-1β, and IL-6. All pre-treatments decreased the expression of COX-2 and TNF-α, with psilocybin alone and in 1:50 combination, with eugenol being the most effective. In the post-treatment, all combinations of psilocybin and eugenol were effective in reducing inflammation, with the 1:50 ratio displaying the most prominent results in reducing the mRNA content of tested cytokines. Western blot analysis confirmed the effect on COX-2 and IL-1β proteins. Finally, the ELISA showed that post-treatment with psilocybin + eugenol (1:50) demonstrated the best results, decreasing the expression of multiple markers including IL-6 and IL-8. This demonstrates the anti-inflammatory effects of a combination of psilocybin and eugenol in the brain of animals with systemically induced inflammation.
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spelling pubmed-100561232023-03-30 The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice Zanikov, Timur Gerasymchuk, Marta Ghasemi Gojani, Esmaeel Robinson, Gregory Ian Asghari, Shima Groves, Alyssa Haselhorst, Lucie Nandakumar, Sanjana Stahl, Cora Cameron, Mackenzie Li, Dongping Rodriguez-Juarez, Rocio Snelling, Alexandra Hudson, Darryl Fiselier, Anna Kovalchuk, Olga Kovalchuk, Igor Molecules Article Inflammation is an organism’s biological defense mechanism. Acute and chronic inflammation of the body triggers the production of pro- and anti-inflammatory pathways that can affect the content of cytokines in the brain and thus cause brain inflammation. Disorders such as depression and posttraumatic stress disorder (PTSD) are often associated with elevated inflammation. Recently, positive and promising clinical results of psilocybin for the treatment of depression and PTSD were reported. Thus, we decided to test whether psilocybin alone or in combination with eugenol, an anti-inflammatory and antioxidant agent, would prevent the increase in or decrease the content of cytokines in the brain of C57BL/6J mice injected with lipopolysaccharides (LPS). Two experiments were performed, one with pre-treatment of mice through gavage with psilocybin (0.88 mg/kg), eugenol (17.6 mg/kg), or combinations of psilocybin and eugenol (1:10, 1:20, or 1:50), followed by intraperitoneal injection of LPS, and the second, post-treatment, with initial injection with LPS, followed by treatment with psilocybin, eugenol, or their combination. Brain tissues were collected, and cytokines were analyzed by qRT-PCR, Western blot, and ELISA. Data were analyzed with a one-way ANOVA followed by Tukey’s post hoc test or with multiple unpaired t-tests. LPS upregulated mRNA expression of COX-2, TNF-α, IL-1β, and IL-6. All pre-treatments decreased the expression of COX-2 and TNF-α, with psilocybin alone and in 1:50 combination, with eugenol being the most effective. In the post-treatment, all combinations of psilocybin and eugenol were effective in reducing inflammation, with the 1:50 ratio displaying the most prominent results in reducing the mRNA content of tested cytokines. Western blot analysis confirmed the effect on COX-2 and IL-1β proteins. Finally, the ELISA showed that post-treatment with psilocybin + eugenol (1:50) demonstrated the best results, decreasing the expression of multiple markers including IL-6 and IL-8. This demonstrates the anti-inflammatory effects of a combination of psilocybin and eugenol in the brain of animals with systemically induced inflammation. MDPI 2023-03-14 /pmc/articles/PMC10056123/ /pubmed/36985596 http://dx.doi.org/10.3390/molecules28062624 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zanikov, Timur
Gerasymchuk, Marta
Ghasemi Gojani, Esmaeel
Robinson, Gregory Ian
Asghari, Shima
Groves, Alyssa
Haselhorst, Lucie
Nandakumar, Sanjana
Stahl, Cora
Cameron, Mackenzie
Li, Dongping
Rodriguez-Juarez, Rocio
Snelling, Alexandra
Hudson, Darryl
Fiselier, Anna
Kovalchuk, Olga
Kovalchuk, Igor
The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice
title The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice
title_full The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice
title_fullStr The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice
title_full_unstemmed The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice
title_short The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice
title_sort effect of combined treatment of psilocybin and eugenol on lipopolysaccharide-induced brain inflammation in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10056123/
https://www.ncbi.nlm.nih.gov/pubmed/36985596
http://dx.doi.org/10.3390/molecules28062624
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