LPS-Induced Liver Inflammation Is Inhibited by Psilocybin and Eugenol in Mice

<b>Background/Objectives:</b> Liver inflammatory diseases are a major global health burden and are often exacerbated by inflammation driven by lipopolysaccharides (LPS) through toll-like receptor 4 signaling. This study evaluates the anti-inflammatory effects of psilocybin and eugenol in...

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Main Authors: Gregory Ian Robinson, Marta Gerasymchuk, Timur Zanikov, Esmaeel Ghasemi Gojani, Shima Asghari, Alyssa Groves, Lucie Haselhorst, Sanjana Nandakumar, Cora Stahl, Ceejay Cruz, Mackenzie Cameron, Yeva Zahoruiko, Dongping Li, Rocio Rodriguez-Juarez, Alex Snelling, Darryl Hudson, Anna Fiselier, Olga Kovalchuk, Igor Kovalchuk
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/4/451
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author Gregory Ian Robinson
Marta Gerasymchuk
Timur Zanikov
Esmaeel Ghasemi Gojani
Shima Asghari
Alyssa Groves
Lucie Haselhorst
Sanjana Nandakumar
Cora Stahl
Ceejay Cruz
Mackenzie Cameron
Yeva Zahoruiko
Dongping Li
Rocio Rodriguez-Juarez
Alex Snelling
Darryl Hudson
Anna Fiselier
Olga Kovalchuk
Igor Kovalchuk
author_facet Gregory Ian Robinson
Marta Gerasymchuk
Timur Zanikov
Esmaeel Ghasemi Gojani
Shima Asghari
Alyssa Groves
Lucie Haselhorst
Sanjana Nandakumar
Cora Stahl
Ceejay Cruz
Mackenzie Cameron
Yeva Zahoruiko
Dongping Li
Rocio Rodriguez-Juarez
Alex Snelling
Darryl Hudson
Anna Fiselier
Olga Kovalchuk
Igor Kovalchuk
author_sort Gregory Ian Robinson
collection DOAJ
description <b>Background/Objectives:</b> Liver inflammatory diseases are a major global health burden and are often exacerbated by inflammation driven by lipopolysaccharides (LPS) through toll-like receptor 4 signaling. This study evaluates the anti-inflammatory effects of psilocybin and eugenol in an LPS-induced liver inflammation model in C57BL/6J mice. <b>Methods:</b> Mice were treated with psilocybin (0.88 mg/kg) and/or eugenol (17.59 mg/kg) either before (pre-treatment) or after (post-treatment) LPS injection. <b>Results:</b> Psilocybin and eugenol, individually and in combination, significantly reduced the LPS-induced mRNA levels of pro-inflammatory cytokines, with post-treatment administration exhibiting stronger effects than pre-treatment. Psilocybin alone displayed the most pronounced anti-inflammatory response, especially for <i>IL-1β</i>, <i>IL-6</i>, and <i>MCP-1</i>, while its combination with eugenol in 1:50 ratio demonstrated similar results, with strongly reduced <i>COX-2</i> and <i>TNF-α</i>. Histological analysis revealed improved nuclear circularity and reduced inflammatory infiltration in the treatment groups. Eugenol alone showed potential adverse effects, including increased <i>MCP-1</i> and <i>GM-CSF</i>, but this was mitigated by the co-administration of psilocybin. <b>Conclusions:</b> These findings highlight psilocybin and its combination with eugenol as promising therapies for hepatic inflammation, suggesting their application in treating acute and chronic liver diseases. Future research should explore their long-term effects, the mechanisms underlying their anti-inflammatory actions, and their therapeutic efficacy in humans.
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spelling doaj-art-a005b872657b4a86b460da7cc90f15882025-08-20T02:18:10ZengMDPI AGPharmaceuticals1424-82472025-03-0118445110.3390/ph18040451LPS-Induced Liver Inflammation Is Inhibited by Psilocybin and Eugenol in MiceGregory Ian Robinson0Marta Gerasymchuk1Timur Zanikov2Esmaeel Ghasemi Gojani3Shima Asghari4Alyssa Groves5Lucie Haselhorst6Sanjana Nandakumar7Cora Stahl8Ceejay Cruz9Mackenzie Cameron10Yeva Zahoruiko11Dongping Li12Rocio Rodriguez-Juarez13Alex Snelling14Darryl Hudson15Anna Fiselier16Olga Kovalchuk17Igor Kovalchuk18Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaGoodCap Pharmaceuticals, 520 3rd Avenue SW, Suite 1900, Calgary, AB T2P 0R3, CanadaGoodCap Pharmaceuticals, 520 3rd Avenue SW, Suite 1900, Calgary, AB T2P 0R3, CanadaCumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, CanadaDepartment of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada<b>Background/Objectives:</b> Liver inflammatory diseases are a major global health burden and are often exacerbated by inflammation driven by lipopolysaccharides (LPS) through toll-like receptor 4 signaling. This study evaluates the anti-inflammatory effects of psilocybin and eugenol in an LPS-induced liver inflammation model in C57BL/6J mice. <b>Methods:</b> Mice were treated with psilocybin (0.88 mg/kg) and/or eugenol (17.59 mg/kg) either before (pre-treatment) or after (post-treatment) LPS injection. <b>Results:</b> Psilocybin and eugenol, individually and in combination, significantly reduced the LPS-induced mRNA levels of pro-inflammatory cytokines, with post-treatment administration exhibiting stronger effects than pre-treatment. Psilocybin alone displayed the most pronounced anti-inflammatory response, especially for <i>IL-1β</i>, <i>IL-6</i>, and <i>MCP-1</i>, while its combination with eugenol in 1:50 ratio demonstrated similar results, with strongly reduced <i>COX-2</i> and <i>TNF-α</i>. Histological analysis revealed improved nuclear circularity and reduced inflammatory infiltration in the treatment groups. Eugenol alone showed potential adverse effects, including increased <i>MCP-1</i> and <i>GM-CSF</i>, but this was mitigated by the co-administration of psilocybin. <b>Conclusions:</b> These findings highlight psilocybin and its combination with eugenol as promising therapies for hepatic inflammation, suggesting their application in treating acute and chronic liver diseases. Future research should explore their long-term effects, the mechanisms underlying their anti-inflammatory actions, and their therapeutic efficacy in humans.https://www.mdpi.com/1424-8247/18/4/451psilocybineugenolpsychedelicsinflammationlipopolysaccharideliver
spellingShingle Gregory Ian Robinson
Marta Gerasymchuk
Timur Zanikov
Esmaeel Ghasemi Gojani
Shima Asghari
Alyssa Groves
Lucie Haselhorst
Sanjana Nandakumar
Cora Stahl
Ceejay Cruz
Mackenzie Cameron
Yeva Zahoruiko
Dongping Li
Rocio Rodriguez-Juarez
Alex Snelling
Darryl Hudson
Anna Fiselier
Olga Kovalchuk
Igor Kovalchuk
LPS-Induced Liver Inflammation Is Inhibited by Psilocybin and Eugenol in Mice
Pharmaceuticals
psilocybin
eugenol
psychedelics
inflammation
lipopolysaccharide
liver
title LPS-Induced Liver Inflammation Is Inhibited by Psilocybin and Eugenol in Mice
title_full LPS-Induced Liver Inflammation Is Inhibited by Psilocybin and Eugenol in Mice
title_fullStr LPS-Induced Liver Inflammation Is Inhibited by Psilocybin and Eugenol in Mice
title_full_unstemmed LPS-Induced Liver Inflammation Is Inhibited by Psilocybin and Eugenol in Mice
title_short LPS-Induced Liver Inflammation Is Inhibited by Psilocybin and Eugenol in Mice
title_sort lps induced liver inflammation is inhibited by psilocybin and eugenol in mice
topic psilocybin
eugenol
psychedelics
inflammation
lipopolysaccharide
liver
url https://www.mdpi.com/1424-8247/18/4/451
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