{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:09:04Z","timestamp":1787612944748,"version":"build-2736575974"},"reference-count":104,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"GoodCap Pharmaceuticals"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Inflammation plays a pivotal role in the development and progression of inflammatory bowel disease (IBD), by contributing to tissue damage and exacerbating the immune response. The investigation of serotonin receptor 2A (5-HT2A) ligands and transient receptor potential (TRP) channel ligands is of significant interest due to their potential to modulate key inflammatory pathways, mitigate the pathological effects of inflammation, and offer new avenues for therapeutic interventions in IBD. This study investigates the anti-inflammatory effects of 5-HT2A ligands, including psilocybin, 4-AcO-DMT, and ketanserin, in combination with TRP channel ligands, including capsaicin, curcumin, and eugenol, on the inflammatory response induced by tumor necrosis factor (TNF)-\u03b1 and interferon (IFN)-\u03b3 in human 3D EpiIntestinal tissue. Enzyme-linked immunosorbent assay was used to assess the expression of pro-inflammatory markers TNF-\u03b1, IFN-\u03b3, IL-6, IL-8, MCP-1, and GM-CSF. Our results show that psilocybin, 4-AcO-DMT, and eugenol significantly reduce TNF-\u03b1 and IFN-\u03b3 levels, while capsaicin and curcumin decrease these markers to a lesser extent. Psilocybin effectively lowers IL-6 and IL-8 levels, but curcumin, capsaicin, and 4-AcO-DMT have limited effects on these markers. In addition, psilocybin can significantly decrease MCP-1 and GM-CSF levels. While ketanserin lowers IL-6 and GM-CSF levels, there are no effects seen on TNF-\u03b1, IFN-\u03b3, IL-8, or MCP-1. Although synergistic effects between 5-HT2A and TRP channel ligands are minimal in this study, the results provide further evidence of the anti-inflammatory effects of psilocybin and eugenol. Further research is needed to understand the mechanisms of action and the feasibility of using these compounds as anti-inflammatory therapies for conditions like IBD.<\/jats:p>","DOI":"10.3390\/life13122345","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T06:53:16Z","timestamp":1702623196000},"page":"2345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8122-2788","authenticated-orcid":false,"given":"Gregory Ian","family":"Robinson","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7260-1938","authenticated-orcid":false,"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahiat","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4037-8086","authenticated-orcid":false,"given":"Marta","family":"Gerasymchuk","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryl","family":"Hudson","sequence":"additional","affiliation":[{"name":"GoodCap Pharmaceuticals, 520 3rd Avenue SW, Suite 1900, Calgary, AB T2P 0R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Kovalchuk","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8137-6928","authenticated-orcid":false,"given":"Igor","family":"Kovalchuk","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lee, J.Y., Wasinger, V.C., Yau, Y.Y., Chuang, E., Yajnik, V., and Leong, R.W. (2018). Molecular Pathophysiology of Epithelial Barrier Dysfunction in Inflammatory Bowel Diseases. Proteomes, 6.","DOI":"10.3390\/proteomes6020017"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3748\/wjg.14.401","article-title":"Role of the intestinal barrier in inflammatory bowel disease","volume":"14","author":"Laukoetter","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"129","DOI":"10.2147\/BTT.S380027","article-title":"A Review on Inflammatory Bowel Diseases: Recent Molecular Pathophysiology Advances","volume":"16","author":"Abdulla","year":"2022","journal-title":"Biol. Targets Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"765474","DOI":"10.3389\/fmed.2021.765474","article-title":"Treatment of Inflammatory Bowel Disease: A Comprehensive Review","volume":"8","author":"Cai","year":"2021","journal-title":"Front. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S2468-1253(19)30333-4","article-title":"The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"5","author":"Alatab","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/jgh.14872","article-title":"The epidemiology of inflammatory bowel disease: East meets west","volume":"35","author":"Mak","year":"2020","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nkadimeng, S.M., Nabatanzi, A., Steinmann, C.M.L., and Eloff, J.N. (2020). Phytochemical, Cytotoxicity, Antioxidant and Anti-Inflammatory Effects of Psilocybe Natalensis Magic Mushroom. Plants, 9.","DOI":"10.3390\/plants9091127"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.2147\/JIR.S317182","article-title":"Anti-Inflammatory Effects of Four Psilocybin-Containing Magic Mushroom Water Extracts in vitro on 15-Lipoxygenase Activity and on Lipopolysaccharide-Induced Cyclooxygenase-2 and Inflammatory Cytokines in Human U937 Macrophage Cells","volume":"14","author":"Nkadimeng","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1080\/09540261.2018.1481827","article-title":"Psychedelics as anti-inflammatory agents","volume":"30","author":"Flanagan","year":"2018","journal-title":"Int. Rev. Psychiatry Abingdon Engl."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kalkman, H.O. (2023). Inhibition of Microglial GSK3\u03b2 Activity Is Common to Different Kinds of Antidepressants: A Proposal for an In Vitro Screen to Detect Novel Antidepressant Principles. Biomedicines, 11.","DOI":"10.3390\/biomedicines11030806"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1021\/acsptsci.0c00176","article-title":"Investigation of the Structure-Activity Relationships of Psilocybin Analogues","volume":"4","author":"Klein","year":"2021","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6743","DOI":"10.3390\/cimb45080427","article-title":"Anti-Inflammatory Effects of Serotonin Receptor and Transient Receptor Potential Channel Ligands in Human Small Intestinal Epithelial Cells","volume":"45","author":"Robinson","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fphar.2016.00068","article-title":"Dual Role of Endogenous Serotonin in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis","volume":"7","author":"Rapalli","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"659","DOI":"10.3892\/ijmm.2016.2486","article-title":"Effects of ketanserin on experimental colitis in mice and macrophage function","volume":"37","author":"Xiao","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/bjp.2008.261","article-title":"The 5-HT2 antagonist ketanserin is an open channel blocker of human cardiac ether-\u00e0-go-go-related gene (hERG) potassium channels","volume":"155","author":"Tang","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_16","unstructured":"Aronson, J.K. (2016). Meyler\u2019s Side Effects of Drugs (Sixteenth Edition), Elsevier."},{"key":"ref_17","first-page":"CD000954","article-title":"Ketanserin for Raynaud\u2019s phenomenon in progressive systemic sclerosis","volume":"1998","author":"Pope","year":"1998","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1187890","DOI":"10.3389\/fimmu.2023.1187890","article-title":"Function of TRP channels in monocytes\/macrophages","volume":"14","author":"Wu","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1111\/bph.13392","article-title":"What is the evidence for the role of TRP channels in inflammatory and immune cells?","volume":"173","author":"Parenti","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"136895","DOI":"10.1016\/j.neulet.2022.136895","article-title":"Effects of peripheral administration of lipopolysaccharide on chronic sickness responses in TRPM8-deficient mice","volume":"790","author":"Horikawa","year":"2022","journal-title":"Neurosci. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Piciu, F., Balas, M., Badea, M.A., and Cucu, D. (2023). TRP Channels in Tumoral Processes Mediated by Oxidative Stress and Inflammation. Antioxidants, 12.","DOI":"10.20944\/preprints202305.1357.v1"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zanikov, T., Gerasymchuk, M., Ghasemi Gojani, E., Robinson, G.I., Asghari, S., Groves, A., Haselhorst, L., Nandakumar, S., Stahl, C., and Cameron, M. (2023). The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice. Molecules, 28.","DOI":"10.3390\/molecules28062624"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2497354","DOI":"10.1155\/2021\/2497354","article-title":"Pharmacological Properties and Health Benefits of Eugenol: A Comprehensive Review","volume":"2021","author":"Nisar","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.molimm.2019.09.020","article-title":"Curcumin inhibits LPS-induced neuroinflammation by promoting microglial M2 polarization via TREM2\/TLR4\/NF-\u03baB pathways in BV2 cells","volume":"116","author":"Zhang","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Karthikeyan, A., Young, K.N., Moniruzzaman, M., Beyene, A.M., Do, K., Kalaiselvi, S., and Min, T. (2021). Curcumin and Its Modified Formulations on Inflammatory Bowel Disease (IBD): The Story So Far and Future Outlook. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13040484"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"EFSA (2010). Panel on Food Additives and Nutrient Sources added to Food (ANS) Scientific Opinion on the re-evaluation of curcumin (E 100) as a food additive. EFSA J., 8, 1679.","DOI":"10.2903\/j.efsa.2010.1679"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Csek\u0151, K., Beckers, B., Keszthelyi, D., and Helyes, Z. (2019). Role of TRPV1 and TRPA1 Ion Channels in Inflammatory Bowel Diseases: Potential Therapeutic Targets?. Pharmaceutics, 12.","DOI":"10.3390\/ph12020048"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8","DOI":"10.14302\/issn.2574-4526.jddd-19-3063","article-title":"Capsaicin: A Potential Therapy Adjuvant for Intestinal Bowel Disease","volume":"2","year":"2019","journal-title":"J. Dig. Disord. Diagn."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.chembiol.2022.06.011","article-title":"Capsaicin ameliorates inflammation in a TRPV1-independent mechanism by inhibiting PKM2-LDHA-mediated Warburg effect in sepsis","volume":"29","author":"Zhang","year":"2022","journal-title":"Cell Chem. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e00470-17","DOI":"10.1128\/mBio.00470-17","article-title":"Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet","volume":"8","author":"Kang","year":"2017","journal-title":"mBio"},{"key":"ref_31","first-page":"1","article-title":"Oral Capsaicin Ingestion: A Brief Update Dose, Tolerance and Side Effects","volume":"5","author":"Arnold","year":"2018","journal-title":"Res. Rev. J. Herb. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1749-6632.1998.tb10180.x","article-title":"Pleiotropic behavior of 5-HT2A and 5-HT2C receptor agonists","volume":"861","author":"Berg","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1007\/s11626-020-00526-6","article-title":"Human small intestinal organotypic culture model for drug permeation, inflammation, and toxicity assays","volume":"57","author":"Markus","year":"2021","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.18632\/aging.202500","article-title":"Fighting the storm: Could novel anti-TNF\u03b1 and anti-IL-6 C. sativa cultivars tame cytokine storm in COVID-19?","volume":"13","author":"Kovalchuk","year":"2021","journal-title":"Aging"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/s41419-021-04151-3","article-title":"TNF-\u03b1 synergises with IFN-\u03b3 to induce caspase-8-JAK1\/2-STAT1-dependent death of intestinal epithelial cells","volume":"12","author":"Woznicki","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nchembio.375","article-title":"COX-2\u2032s new role in inflammation","volume":"6","author":"Chen","year":"2010","journal-title":"Nat. Chem. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and Inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S1074-7613(00)80038-2","article-title":"Impaired On\/Off Regulation of TNF Biosynthesis in Mice Lacking TNF AU-Rich Elements: Implications for Joint and Gut-Associated Immunopathologies","volume":"10","author":"Kontoyiannis","year":"1999","journal-title":"Immunity"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1136\/gutjnl-2017-315671","article-title":"Expansion of IL-23 receptor bearing TNFR2+ T cells is associated with molecular resistance to anti-TNF therapy in Crohn\u2019s disease","volume":"68","author":"Schmitt","year":"2019","journal-title":"Gut"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41577-018-0029-z","article-title":"IFN\u03b3: Signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy","volume":"18","author":"Ivashkiv","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2934","DOI":"10.1128\/MCB.05445-11","article-title":"NF-kappaB protects cells from gamma interferon-induced RIP1-dependent necroptosis","volume":"31","author":"Thapa","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"E3109","DOI":"10.1073\/pnas.1301218110","article-title":"Interferon-induced RIP1\/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases","volume":"110","author":"Thapa","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.4049\/jimmunol.1900216","article-title":"ZBP1\/DAI Drives RIPK3-Mediated Cell Death Induced by IFNs in the Absence of RIPK1","volume":"203","author":"Ingram","year":"2019","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.4049\/jimmunol.157.3.1261","article-title":"Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn\u2019s disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5","volume":"157","author":"Fuss","year":"1996","journal-title":"J. Immunol."},{"key":"ref_45","first-page":"127","article-title":"Interleukin-2- and interferon-gamma-secreting T cells in normal and diseased human intestinal mucosa","volume":"78","author":"Breese","year":"1993","journal-title":"Immunology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1097\/00054725-199811000-00005","article-title":"Altered expression of interferon-gamma and interleukin-4 in inflammatory bowel disease","volume":"4","author":"Camoglio","year":"1998","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1365-2249.1991.tb05592.x","article-title":"Triggered human mucosal T cells release tumour necrosis factor-alpha and interferon-gamma which kill human colonic epithelial cells","volume":"83","author":"Deem","year":"1991","journal-title":"Clin. Exp. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6164","DOI":"10.4049\/jimmunol.171.11.6164","article-title":"Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms","volume":"171","author":"Bruewer","year":"2003","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1136\/gut.36.1.45","article-title":"Soluble interleukin-6 receptors in inflammatory bowel disease: Relation to circulating interleukin-6","volume":"36","author":"Mitsuyama","year":"1995","journal-title":"Gut"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/75068","article-title":"Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: Evidence in Crohn disease and experimental colitis in vivo","volume":"6","author":"Atreya","year":"2000","journal-title":"Nat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"921","DOI":"10.2174\/1381612822666161006151605","article-title":"Curcumin: An Effective Inhibitor of Interleukin-6","volume":"23","author":"Ghandadi","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"155541","DOI":"10.1016\/j.cyto.2021.155541","article-title":"Effect of curcumin on proinflammatory cytokines: A meta-analysis of randomized controlled trials","volume":"143","author":"Gorabi","year":"2021","journal-title":"Cytokine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.4049\/jimmunol.0804012","article-title":"Monocyte Chemoattractant Protein-1 Contributes to Gut Homeostasis and Intestinal Inflammation by Composition of IL-10\u2013Producing Regulatory Macrophage Subset","volume":"184","author":"Takada","year":"2010","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.fct.2009.09.013","article-title":"Curcumin inhibits phorbol myristate acetate (PMA)-induced MCP-1 expression by inhibiting ERK and NF-kappaB transcriptional activity","volume":"48","author":"Lim","year":"2010","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.cytogfr.2016.10.001","article-title":"Curcumin as a natural regulator of monocyte chemoattractant protein-1","volume":"33","author":"Karimian","year":"2017","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/gtc.13008","article-title":"GM-CSF-producing CCR2+ CCR6+ Th17 cells are pathogenic in dextran sodium sulfate-induced colitis model in mice","volume":"28","author":"Ariki","year":"2023","journal-title":"Genes Cells"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/nri.2017.86","article-title":"Innate lymphoid cells: Major players in inflammatory diseases","volume":"17","author":"Ebbo","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s12026-022-09350-4","article-title":"Immunostimulatory activity of fluoxetine in macrophages via regulation of the PI3K and P38 signaling pathways","volume":"71","author":"Yetkin","year":"2023","journal-title":"Immunol. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"715469","DOI":"10.3389\/fphys.2021.715469","article-title":"Capsaicin Attenuates Lipopolysaccharide-Induced Inflammation and Barrier Dysfunction in Intestinal Porcine Epithelial Cell Line-J2","volume":"12","author":"Zhao","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Azimirad, M., Noori, M., Azimirad, F., Gholami, F., Naseri, K., Yadegar, A., Asadzadeh Aghdaei, H., and Zali, M.R. (2022). Curcumin and capsaicin regulate apoptosis and alleviate intestinal inflammation induced by Clostridioides difficile in vitro. Ann. Clin. Microbiol. Antimicrob., 21.","DOI":"10.1186\/s12941-022-00533-3"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Cione, E., Plastina, P., Pingitore, A., Perri, M., Caroleo, M.C., Fazio, A., Witkamp, R., and Meijerink, J. (2019). Capsaicin Analogues Derived from n-3 Polyunsaturated Fatty Acids (PUFAs) Reduce Inflammatory Activity of Macrophages and Stimulate Insulin Secretion by \u03b2-Cells In Vitro. Nutrients, 11.","DOI":"10.3390\/nu11040915"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.taap.2018.09.025","article-title":"TRPV1 mediates capsaicin-stimulated metabolic activity but not cell death or inhibition of interleukin-1\u03b2 release in human THP-1 monocytes","volume":"360","author":"Kunde","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"102125","DOI":"10.1016\/j.pupt.2022.102125","article-title":"Inflammatory and contractile profile in LPS-challenged equine isolated bronchi: Evidence for IL-6 as a potential target against AHR in equine asthma","volume":"73\u201374","author":"Calzetta","year":"2022","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"17690","DOI":"10.1038\/s41598-021-96736-3","article-title":"LSD-stimulated behaviors in mice require \u03b2-arrestin 2 but not \u03b2-arrestin 1","volume":"11","author":"Rodriguiz","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/gene.2015.37","article-title":"Multifaceted role of \u03b2-arrestins in inflammation and disease","volume":"16","author":"Sharma","year":"2015","journal-title":"Genes Immun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.bcp.2017.09.008","article-title":"Free-fatty acid receptor-4 (FFA4) modulates ROS generation and COX-2 expression via the C-terminal \u03b2-arrestin phosphosensor in Raw 264.7 macrophages","volume":"146","author":"Cheshmehkani","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1002\/ptr.7768","article-title":"Eugenol promotes appetite through TRP channels mediated-CaMKK2\/AMPK signaling pathway","volume":"37","author":"Huang","year":"2023","journal-title":"Phytother. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1038\/s41467-019-10424-5","article-title":"CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer","volume":"10","author":"Racioppi","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jconrel.2021.05.028","article-title":"In vitro models replicating the human intestinal epithelium for absorption and metabolism studies: A systematic review","volume":"335","author":"Fedi","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1126\/science.abl8615","article-title":"Structure-based discovery of nonhallucinogenic psychedelic analogs","volume":"375","author":"Cao","year":"2022","journal-title":"Science"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.neuron.2007.01.008","article-title":"Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior","volume":"53","author":"Weisstaub","year":"2007","journal-title":"Neuron"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.freeradbiomed.2013.07.045","article-title":"The protective action of ketanserin against lipopolysaccharide-induced shock in mice is mediated by inhibiting inducible NO synthase expression via the MEK\/ERK pathway","volume":"65","author":"Liu","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"11107","DOI":"10.1073\/pnas.95.19.11107","article-title":"Rapid inhibition of interleukin-6 signaling and Stat3 activation mediated by mitogen-activated protein kinases","volume":"95","author":"Sengupta","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1007\/s00296-008-0564-1","article-title":"Serotonin mediates PGE2 overexpression through 5-HT2A and 5-HT3 receptor subtypes in serum-free tissue culture of macrophage-like synovial cells","volume":"28","author":"Seidel","year":"2008","journal-title":"Rheumatol. Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/intimm\/dxg027","article-title":"Differential effect of serotonin on cytokine production in lipopolysaccharide-stimulated human peripheral blood mononuclear cells: Involvement of 5-hydroxytryptamine2A receptors","volume":"15","author":"Venters","year":"2003","journal-title":"Int. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/00001721-199603000-00004","article-title":"Serotonin stimulates megakaryocytopoiesis via the 5-HT2 receptor","volume":"7","author":"Yang","year":"1996","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"577608","DOI":"10.1016\/j.jneuroim.2021.577608","article-title":"The role of 5-HT2B-receptors in fluoxetine-mediated modulation of Th17- and Th1-cells in multiple sclerosis","volume":"356","author":"Sviridova","year":"2021","journal-title":"J. Neuroimmunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.euroneuro.2013.12.006","article-title":"Psilocybin\u2014Summary of knowledge and new perspectives","volume":"24","year":"2014","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1021\/acsptsci.3c00123","article-title":"Transient Elevation of Plasma Glucocorticoids Supports Psilocybin-Induced Anxiolysis in Mice","volume":"6","author":"Jones","year":"2023","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Liu, N., Sun, S., Wang, P., Sun, Y., Hu, Q., and Wang, X. (2021). The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157931"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Bischoff, S.C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J.-D., Serino, M., Tilg, H., Watson, A., and Wells, J.M. (2014). Intestinal permeability\u2014A new target for disease prevention and therapy. BMC Gastroenterol., 14.","DOI":"10.1186\/s12876-014-0189-7"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1093\/jn\/nxaa129","article-title":"Dietary L-Tryptophan Regulates Colonic Serotonin Homeostasis in Mice with Dextran Sodium Sulfate-Induced Colitis","volume":"150","author":"Wang","year":"2020","journal-title":"J. Nutr."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Koopman, N., Katsavelis, D., ten Hove, A.S., Brul, S., de Jonge, W.J., and Seppen, J. (2021). The Multifaceted Role of Serotonin in Intestinal Homeostasis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179487"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Nau, F., Yu, B., Martin, D., and Nichols, C.D. (2013). Serotonin 5-HT2A Receptor Activation Blocks TNF-\u03b1 Mediated Inflammation In Vivo. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075426"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3928","DOI":"10.7150\/thno.70762","article-title":"5-HT2B-mediated serotonin activation in enterocytes suppresses colitis-associated cancer initiation and promotes cancer progression","volume":"12","author":"Mao","year":"2022","journal-title":"Theranostics"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"26","DOI":"10.5217\/ir.2018.16.1.26","article-title":"Immunological pathogenesis of inflammatory bowel disease","volume":"16","author":"Lee","year":"2018","journal-title":"Intest. Res."},{"key":"ref_87","unstructured":"Zinberg, N.E. (1986). Drug, Set, and Setting: The Basis for Controlled Intoxicant Use, Yale University Press."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1177\/02698811211069100","article-title":"Adverse effects of psychedelics: From anecdotes and misinformation to systematic science","volume":"36","author":"Schlag","year":"2022","journal-title":"J. Psychopharmacol. Oxf. Engl."},{"key":"ref_89","first-page":"e31796","article-title":"Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis","volume":"14","author":"Irizarry","year":"2022","journal-title":"Cureus"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.neubiorev.2020.09.035","article-title":"Potential safety, benefits, and influence of the placebo effect in microdosing psychedelic drugs: A systematic review","volume":"119","author":"Ona","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2045125320950567","DOI":"10.1177\/2045125320950567","article-title":"The therapeutic potential of microdosing psychedelics in depression","volume":"10","author":"Kuypers","year":"2020","journal-title":"Ther. Adv. Psychopharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1080\/14740338.2022.1986001","article-title":"Safety considerations for prescribing SSRI antidepressants to patients at increased cardiovascular risk","volume":"21","author":"Mortensen","year":"2022","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1097\/JCP.0000000000001608","article-title":"A Critical Appraisal of Evidence on the Efficacy and Safety of Serotonergic Psychedelic Drugs as Emerging Antidepressants: Mind the Evidence Gap","volume":"42","author":"Ledwos","year":"2022","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1177\/07067437221111371","article-title":"The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: Serotonergic Psychedelic Treatments for Major Depressive Disorder","volume":"68","author":"Rosenblat","year":"2023","journal-title":"Can. J. Psychiatry"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"117415","DOI":"10.1016\/j.jep.2023.117415","article-title":"Antidepressant- and anxiolytic-like activities and acute toxicity evaluation of the Psilocybe cubensis mushroom in experimental models in mice","volume":"320","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1615\/JLongTermEffMedImplants.2015011871","article-title":"The mechanobiology of drug-induced cardiac valve disease","volume":"25","author":"Lam","year":"2015","journal-title":"J. Long. Term Eff. Med. Implants"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1080\/14740338.2023.2248883","article-title":"Serotonin 5-HT2B receptor agonism and valvular heart disease: Implications for the development of psilocybin and related agents","volume":"22","author":"McIntyre","year":"2023","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.euroneuro.2016.05.001","article-title":"Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens","volume":"26","author":"Rickli","year":"2016","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"24888","DOI":"10.1021\/acsomega.2c03476","article-title":"Synthesis, Structural Characterization, and Pharmacological Activity of Novel Quaternary Salts of 4-Substituted Tryptamines","volume":"7","author":"Glatfelter","year":"2022","journal-title":"ACS Omega"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1002\/cpdd.796","article-title":"Exposure-Response Analysis to Assess the Concentration-QTc Relationship of Psilocybin\/Psilocin","volume":"10","author":"Dahmane","year":"2021","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_101","first-page":"473","article-title":"Serotonin Signaling in the Gastrointestinal Tract: Nat","volume":"10","author":"Mawe","year":"2013","journal-title":"Rev. Gastroenterol. Hepatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"G877","DOI":"10.1152\/ajpgi.00435.2001","article-title":"5-HT2A receptors: Location and functional analysis in intestines of wild-type and 5-HT2A knockout mice","volume":"282","author":"Hen","year":"2002","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Panpetch, W., Visitchanakun, P., Saisorn, W., Sawatpanich, A., Chatthanathon, P., Somboonna, N., Tumwasorn, S., and Leelahavanichkul, A. (2021). Lactobacillus rhamnosus attenuates Thai chili extracts induced gut inflammation and dysbiosis despite capsaicin bactericidal effect against the probiotics, a possible toxicity of high dose capsaicin. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0261189"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jnutbio.2018.12.005","article-title":"Macrophage plasticity, polarization and function in response to curcumin, a diet-derived polyphenol, as an immunomodulatory agent","volume":"66","author":"Mohammadi","year":"2019","journal-title":"J. Nutr. Biochem."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/12\/2345\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:39:23Z","timestamp":1760132363000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/12\/2345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,15]]},"references-count":104,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["life13122345"],"URL":"https:\/\/doi.org\/10.3390\/life13122345","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,15]]}}}