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Authors = Sanjana Nandakumar

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24 pages, 6173 KiB  
Article
LPS-Induced Liver Inflammation Is Inhibited by Psilocybin and Eugenol in Mice
by 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 and Igor Kovalchuk
Pharmaceuticals 2025, 18(4), 451; https://doi.org/10.3390/ph18040451 - 23 Mar 2025
Viewed by 1221
Abstract
Background/Objectives: 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 [...] Read more.
Background/Objectives: 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. Methods: 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. Results: 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 IL-1β, IL-6, and MCP-1, while its combination with eugenol in 1:50 ratio demonstrated similar results, with strongly reduced COX-2 and TNF-α. Histological analysis revealed improved nuclear circularity and reduced inflammatory infiltration in the treatment groups. Eugenol alone showed potential adverse effects, including increased MCP-1 and GM-CSF, but this was mitigated by the co-administration of psilocybin. Conclusions: 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. Full article
(This article belongs to the Section Pharmacology)
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19 pages, 4126 KiB  
Article
The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice
by Timur Zanikov, Marta Gerasymchuk, Esmaeel Ghasemi Gojani, Gregory Ian Robinson, Shima Asghari, Alyssa Groves, Lucie Haselhorst, Sanjana Nandakumar, Cora Stahl, Mackenzie Cameron, Dongping Li, Rocio Rodriguez-Juarez, Alexandra Snelling, Darryl Hudson, Anna Fiselier, Olga Kovalchuk and Igor Kovalchuk
Molecules 2023, 28(6), 2624; https://doi.org/10.3390/molecules28062624 - 14 Mar 2023
Cited by 33 | Viewed by 7950
Abstract
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 [...] Read more.
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. Full article
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26 pages, 6307 KiB  
Article
Phytocannabinoids Stimulate Rejuvenation and Prevent Cellular Senescence in Human Dermal Fibroblasts
by Marta Gerasymchuk, Gregory Ian Robinson, Alyssa Groves, Lucie Haselhorst, Sanjana Nandakumar, Cora Stahl, Olga Kovalchuk and Igor Kovalchuk
Cells 2022, 11(23), 3939; https://doi.org/10.3390/cells11233939 - 6 Dec 2022
Cited by 23 | Viewed by 26812
Abstract
In light of the increased popularity of phytocannabinoids (pCBs) and their appearance in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of pCBs in skin rejuvenation. Utilizing healthy and stress-induced premature senescent (SIPS) CCD-1064Sk skin [...] Read more.
In light of the increased popularity of phytocannabinoids (pCBs) and their appearance in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of pCBs in skin rejuvenation. Utilizing healthy and stress-induced premature senescent (SIPS) CCD-1064Sk skin fibroblasts, the effects of pCBs on cellular viability, functional activity, metabolic function, and nuclear architecture were tested. Both delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) within the range of 0.5 µM to 2.0 µM increased cell growth in a dose-dependent manner while significantly decreasing senescence as measured by beta-galactosidase activity. Utilizing a scratch assay, both THC and CBD (2.0 µM) significantly improved wound healing in both healthy and SIPS fibroblasts. THC and CBD altered nuclear architecture and mRNA levels of cell cycle regulators and genes involved in ECM production. Subsequently, we found ELN, Cyclin D1, PCNA, and BID protein levels altered by SIPS but ameliorated after pCBs exposure in human dermal fibroblasts. Lastly, we compared the efficacy of THC and CBD with common anti-aging nutrient signaling regulators in replicative senescent adult human dermal fibroblasts, CCD-1135Sk. Both THC and CBD were found to improve wound healing better than metformin, rapamycin, and triacetylresveratrol in replicative senescent CCD-1135Sk fibroblasts. Therefore, pCBs can be a valuable source of biologically active substances used in cosmetics, and more studies using clinical trials should be performed to confirm the efficacy of phytocannabinoids. Full article
(This article belongs to the Special Issue Molecular and Cell Basis of Skin Diseases and Aging)
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