Anti-Inflammatory Effects of Serotonin Receptor and Transient Receptor Potential Channel Ligands in Human Small Intestinal Epithelial Cells
Gregory Ian Robinson, Dongping Li, Bo Wang, Yeva Zahoruiko, Marta Gerasymchuk, Darryl Hudson, Olga Kovalchuk, Igor Kovalchuk
Current Issues in Molecular Biology August 15, 2023 DOI: 10.3390/cimb45080427 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Human small intestinal epithelial cells (HSEIC) |
| Interventions | Psilocybin 4-Acetoxy-N N-dimethyltryptamine Ketanserin Capsaicin Curcumin Eugenol |
| Duration | 24 to 96 h |
| Topics | Serotonin |
| Keywords | 5-HT Receptor Transient computer programming Cell biology Channel broadcasting Endocrinology |
| Citations | 20 |
| Key findings | Combined psilocybin and eugenol reduced COX-2 by 19-fold and IL-6 by 10-fold in inflamed human small intestinal epithelial cells without cytotoxicity. |
Abstract
Intestinal inflammation and dysbiosis can lead to inflammatory bowel diseases (IBD) and systemic inflammation, affecting multiple organs. Developing novel anti-inflammatory therapeutics is crucial for preventing IBD progression. Serotonin receptor type 2A (5-HT2A) ligands, including psilocybin (Psi), 4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), and ketanserin (Ket), along with transient receptor potential (TRP) channel ligands like capsaicin (Cap), curcumin (Cur), and eugenol (Eug), show promise as anti-inflammatory agents. In this study, we investigated the cytotoxic and anti-inflammatory effects of Psi, 4-AcO-DMT, Ket, Cap, Cur, and Eug on human small intestinal epithelial cells (HSEIC). HSEIC were exposed to tumor necrosis factor (TNF)-α and interferon (IFN)-γ for 24 h to induce an inflammatory response, followed by treatment with each compound at varying doses (0–800 μM) for 24 to 96 h. The cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and protein expression by Western blot (WB) analysis. As single treatments, Psi (40 μM), Cur (0.5 μM), and Eug (50 μM) significantly reduced COX-2 levels without cytotoxic effects. When combined, Psi (40 μM) and Cur (0.5 μM) exhibited synergy, resulting in a substantial decrease in COX-2 protein levels (−28× fold change), although the reduction in IL-6 was less pronounced (−1.6× fold change). Psi (20 μM) and Eug (25 μM) demonstrated the most favorable outcomes, with significant decreases in COX-2 (−19× fold change) and IL-6 (−10× fold change) protein levels. Moreover, the combination of Psi and Eug did not induce cytotoxic effects in vitro at any tested doses. This study is the first to explore the anti-inflammatory potential of psilocybin and 4-AcO-DMT in the intestines while highlighting the potential for synergy between the 5-HT2A and TRP channel ligands, specifically Psi and Eug, in alleviating the TNF-α/IFN-γ-induced inflammatory response in HSEIC. Further investigations should evaluate if the Psi and Eug combination has the therapeutic potential to treat IBD in vivo.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 12
- A Comprehensive Review of the Current Status of the Cellular Neurobiology of Psychedelics Biology October 28, 2023
- Do the therapeutic effects of psilocybin involve actions in the gut? TIPS - Trends in Pharmacological Sciences February 1, 2024
- The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies Progress in Neuro-Psychopharmacology and Biological Psychiatry September 7, 2024
- Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue Life December 15, 2023
- Therapeutic modulation of the kynurenine pathway in severe mental illness and comorbidities: A potential role for serotonergic psychedelics. Progress in Neuro-Psychopharmacology and Biological Psychiatry August 30, 2024
and 7 more in the library
Cites 17
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psychedelics as Medicines: An Emerging New Paradigm Clinical Pharmacology & Therapeutics November 4, 2016
- Structure-based discovery of nonhallucinogenic psychedelic analogs Science January 27, 2022
- Psychedelics as anti-inflammatory agents International Review of Psychiatry July 4, 2018
- Transient Stimulation with Psychoplastogens Is Sufficient to Initiate Neuronal Growth ACS Pharmacology & Translational Science September 11, 2020
and 12 more in the library