International Immunopharmacology
February 23, 2024
Salma Laabi, Claire LeMmon, Callie Vogel et al.
16 citations
Psilocybin and its active metabolite psilocin show different cytotoxic and immunomodulatory effects on mouse macrophages. Psilocybin is nearly twice as cytotoxic as psilocin, with LC50 values of 12 ng/ml and 28 ng/ml, respectively. In resting macrophages, both compounds triggered significant release of the pro-inflammatory cytokine TNF-α after 4 hours, with lower doses inducing higher levels than higher doses. Only the highest dose of psilocin increased the anti-inflammatory cytokine IL-10 in resting cells. In LPS-activated macrophages, psilocin reduced TNF-α more than psilocybin in both pre-treatment and post-treatment. Psilocin, but not psilocybin, significantly increased IL-10 in post-treatment, indicating that psilocin exerts anti-inflammatory effects on classically activated macrophages.
International Immunopharmacology
June 26, 2025
Salma Laabi, Claire LeMmon, Callie Vogel et al.
15 citations
Psilocybin and its active metabolite psilocin suppress the pro-inflammatory cytokine TNF-α and increase levels of the neuroplasticity marker BDNF in activated microglia. These effects are mediated through 5-HT2A, 5-HT2B, 5-HT7, and TrkB signaling. AhR activation is required for psilocin-induced BDNF upregulation but not for TNF-α suppression. IL-10 levels remain unchanged under normal conditions but rise when serotonergic, TrkB, or AhR signaling is blocked, indicating a compensatory anti-inflammatory shift. The compounds promote a microglial phenotype that reduces inflammation and supports neuroplasticity via distinct receptor-specific pathways.
International Immunopharmacology
September 30, 2024
San-Ying Cai, Ang Liu, Wen-Xi Xie et al.
13 citations
In a rat model of chronic obstructive pulmonary disease (COPD) receiving mechanical ventilation, esketamine reduced lung injury by dampening inflammation and oxidative stress. Rats given esketamine showed lower lung water content, reduced permeability, and decreased levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-8) while increasing the anti-inflammatory cytokine IL-10. The drug also lowered markers of oxidative stress (malondialdehyde and myeloperoxidase) and raised the antioxidant enzyme superoxide dismutase. These effects were linked to reduced activation of the MAPK and NF-κB signaling pathways. Esketamine appears to protect lung tissue in ventilated COPD rats through these mechanisms.
International Immunopharmacology
August 1, 2026
Jinghua Zhao, Ruxin Zhang, Jiarui Pan et al.
The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) reduces depression-like behavior in mice by suppressing neuroinflammation and neuronal pyroptosis. In experiments with male C57BL/6J mice and PC12 cells, HNK lowered expression of NLRP3, caspase-1, GSDMD, and interleukin-1β at both protein and mRNA levels, lessened neuronal injury, and reduced lactate dehydrogenase release. Transcriptomic analysis identified Vcam1 as a key differentially expressed gene. Overexpressing Vcam1 increased pyroptosis markers, while HNK reduced Vcam1 expression; knocking down Vcam1 had opposite effects. HNK thus attenuates LPS-induced pyroptosis and neuroinflammation partly by downregulating the Vcam1/caspase-1/IL-1β pathway, offering insights for depression treatment.
International Immunopharmacology
May 5, 2023
Zhi-Heng Zheng, Xing-Cheng Lin, Ying-ling Lu et al.
Harmine, a compound found in certain medicinal plants, reduces anxiety-like behaviors in mice by calming brain inflammation and restoring normal nerve cell activity. In a mouse model where anxiety was triggered by a bacterial immune challenge, harmine lowered levels of inflammatory proteins IL-1β and TNF-α in the brain. It also corrected an overactive connection between the medial prefrontal cortex and the basolateral amygdala, rebalancing excitatory and inhibitory signals. Additionally, harmine reduced the heightened excitability of amygdala neurons. These results suggest harmine may work as an anxiety treatment by both reducing neuroinflammation and reversing stress-related changes in brain cell communication.
International Immunopharmacology
August 1, 2019
Daiyue Chang, Jinghua Zhao, Xintong Zhang et al.
Ketamine combined with docosahexaenoic acid (DHA), an unsaturated fatty acid, reversed depression-like behaviors in rats exposed to lipopolysaccharide, an inflammatory trigger. The combination reduced immobility time in forced swimming and tail suspension tests and increased sucrose preference more effectively than either agent alone. It also reversed nerve damage, reduced inflammatory cytokines IL-1, IL-6, and TNF-α in the hippocampus and PC12 cells, increased brain-derived neurotrophic factor (BDNF), inhibited PP65 nuclear translocation, and suppressed NF-κB expression while increasing P-CREB and BDNF. The findings suggest that combining ketamine with DHA may offer a more effective treatment for inflammation-driven depression by inhibiting inflammatory pathways.