{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:07:48Z","timestamp":1789420068168,"version":"build-2803163510"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Neuroinflammation plays a central role in neurodegenerative diseases such as Alzheimer\u2019s and Parkinson\u2019s, along with depression, anxiety, and infectious diseases including COVID-19. Harmine and harmaline, \u03b2-carboline alkaloids from\n                      <jats:italic>Banisteriopsis caapi<\/jats:italic>\n                      , exhibit immunomodulatory, anti-inflammatory, and neuroprotective properties. In this study, we aimed not only to investigate the anti-inflammatory and neuroprotective effects of \u03b2-carbolines and\n                      <jats:italic>B. caapi<\/jats:italic>\n                      extract on a lipopolysaccharide (LPS)-induced neuroinflammation model using SH-SY5Y cells and their impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor expression but also to compare cytokine levels in plasma from intensive care unit (ICU) and non-ICU COVID-19 patients, thereby providing clinical context for the inflammatory response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      SH-SY5Y cells were treated with LPS and incubated with harmine, harmaline, or\n                      <jats:italic>B. caapi<\/jats:italic>\n                      extract. Cell viability was assessed using the MTT assay. Cytokine expression was quantified by ELISA, and receptor gene expression was analyzed using RT-qPCR. Plasma was obtained from the Hospital das Cl\u00ednicas of the University of S\u00e3o Paulo Medical School (HCFMUSP) biobank.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IL-6 was high in ICU patients; LPS increased IL-6 and TNF-\u03b1 cytokine levels in cells, whereas harmine and harmaline significantly reduced both cytokines.\n                      <jats:italic>B. caapi<\/jats:italic>\n                      extract decreased LPS-induced NF-\u03baB and TNF-\u03b1 but did not affect IL-6. Harmine also reduced NF-\u03baB expression. None of the treatments altered TMPRSS11D or furin, and harmaline showed no effect on ACE2. In contrast, the extract upregulated ACE2, whereas harmine induced a modest increase. Only harmine and harmaline reduced TMPRSS2 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      \u03b2-carbolines and\n                      <jats:italic>B. caapi<\/jats:italic>\n                      extract attenuate LPS-induced cytokine production in SH-SY5Y cells, supporting their anti-inflammatory and neuroprotective potential. The extract and \u03b2-carbolines also modulate ACE2 and TMPRSS2 expressions, suggesting relevance to mechanisms associated with neuro-COVID.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1703727","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T08:54:51Z","timestamp":1769417691000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Anti-inflammatory effects of Banisteriopsis caapi and beta-carbolines in neuronal cells: potential implications for neuro-COVID"],"prefix":"10.3389","volume":"16","author":[{"given":"Laura Seixas","family":"Bianco","sequence":"first","affiliation":[{"name":"Department of Physiological Sciences, Santa Casa de S\u00e3o Paulo School of Medical Sciences","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago","family":"Nicoliche","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, Santa Casa de S\u00e3o Paulo School of Medical Sciences","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson Francisco","family":"Corr\u00eaa-Neto","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, Santa Casa de S\u00e3o Paulo School of Medical Sciences","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Lanaro","sequence":"additional","affiliation":[{"name":"Poison Control Center, Faculty of Medical Sciences, State University of Campinas (UNICAMP)","place":["Campinas, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariadiny L.","family":"Caetano","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, Santa Casa de S\u00e3o Paulo School of Medical Sciences","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla Maximo","family":"Prado","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Federal University of S\u00e3o Paulo (UNIFESP)","place":["Santos, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Portes","family":"Ureshino","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Federal University of S\u00e3o Paulo (UNIFESP)","place":["Diadema, Brazil"]},{"name":"Laboratory of Molecular and Translational Endocrinology, Escola Paulista de Medicina, Federal University of S\u00e3o Paulo (UNIFESP)","place":["S\u00e3o Paulo, SP, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda de F\u00e1tima Lopes Calvo","family":"Tib\u00e9rio","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of S\u00e3o Paulo (USP)","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato Fraga","family":"Righetti","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of S\u00e3o Paulo (USP)","place":["S\u00e3o Paulo, Brazil"]},{"name":"Rehabilitation Service, Hospital S\u00edrio-Liban\u00eas","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta Sessa","family":"Stilhano","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, Santa Casa de S\u00e3o Paulo School of Medical Sciences","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Linardi","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, Santa Casa de S\u00e3o Paulo School of Medical Sciences","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1379431","DOI":"10.3389\/fnagi.2024.1379431","article-title":"Investigating the potential neuroprotective benefits of taurine and dihydrotestosterone and hydroxyprogesterone levels in SH-SY5Y cells","volume":"16","author":"Almohaimeed","year":"2024","journal-title":"Front. 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