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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10056123 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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