Robinson Gregory Ian, Gerasymchuk Marta, Zanikov Timur, Gojani Esmaeel Ghasemi, Asghari Shima, Groves Alyssa, Haselhorst Lucie, Nandakumar Sanjana, Stahl Cora, Cruz Ceejay, Cameron Mackenzie, Zahoruiko Yeva, Li Dongping, Rodriguez-Juarez Rocio, Snelling Alex, Hudson Darryl, Fiselier Anna, Kovalchuk Olga, Kovalchuk Igor
Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada.
Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Pharmaceuticals (Basel). 2025 Mar 23;18(4):451. doi: 10.3390/ph18040451.
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. 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. 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 , , and , while its combination with eugenol in 1:50 ratio demonstrated similar results, with strongly reduced and . Histological analysis revealed improved nuclear circularity and reduced inflammatory infiltration in the treatment groups. Eugenol alone showed potential adverse effects, including increased and , but this was mitigated by the co-administration of psilocybin. 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.
肝脏炎症性疾病是全球主要的健康负担，脂多糖（LPS）通过Toll样受体4信号传导驱动的炎症常常会加剧这种负担。本研究评估了裸盖菇素和丁香酚在C57BL/6J小鼠LPS诱导的肝脏炎症模型中的抗炎作用。在LPS注射前（预处理）或后（后处理），用裸盖菇素（0.88mg/kg）和/或丁香酚（17.59mg/kg）对小鼠进行治疗。裸盖菇素和丁香酚单独使用及联合使用时，均能显著降低LPS诱导的促炎细胞因子mRNA水平，后处理给药的效果比预处理更强。单独使用裸盖菇素表现出最显著的抗炎反应，尤其是对[此处原文缺失具体细胞因子名称]、[此处原文缺失具体细胞因子名称]和[此处原文缺失具体细胞因子名称]，而其与丁香酚以1:50比例联合使用时也显示出类似结果，[此处原文缺失具体细胞因子名称]和[此处原文缺失具体细胞因子名称]大幅降低。组织学分析显示，治疗组的细胞核圆形度有所改善，炎症浸润减少。单独使用丁香酚显示出潜在的不良反应，包括[此处原文缺失具体指标名称]和[此处原文缺失具体指标名称]增加，但裸盖菇素的共同给药减轻了这种情况。这些发现突出了裸盖菇素及其与丁香酚的组合作为肝脏炎症有前景的治疗方法，表明它们在治疗急性和慢性肝病中的应用。未来的研究应探索它们的长期影响、抗炎作用的潜在机制以及它们在人类中的治疗效果。
