{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jin SJ"],"funding":["Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries"],"pagination":["2022"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9787735"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(12)"],"pubmed_abstract":["Harmine is a beta-carboline alkaloid present in various plants, including in the seeds of <i>Peganum harmala</i> L. This study aimed to investigate the anti-inflammatory activity and mechanism of harmine using macrophages stimulated with various toll-like receptor (TLR) agonists and a model of endotoxemia. The expression of inflammatory mediators induced by ligands of TLRs 2, 3, 4, and 9 were examined in thioglycollate-elicited peritoneal macrophages isolated from BALB/c and C57BL/6 mouse strains. Further, the activation of NF-κB, MAPK, AP-1, and STAT1 was explored using lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (poly(I:C)). Finally, the liver inflammatory response during endotoxemia was examined. Harmine inhibited inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-12, and other markers induced by various TLR agonists. The inhibition of NF-κB activity by harmine occurred via the modulation of p65 phosphorylation, independent of IκBα degradation. The inhibition of AP-1 activity by harmine was associated with the modulation of JNK. Harmine inhibited the LPS-induced serine and tyrosine phosphorylation of STAT1, but only affected serine phosphorylation by poly(I:C) treatment. In vivo, harmine inhibited iNOS and COX-2 expression during endotoxemia. Collectively, the results show that harmine can be effective against infectious inflammation through modulation of NF-κB, JNK, and STAT1."],"journal":["Life (Basel, Switzerland)"],"pubmed_title":["Harmine Inhibits Multiple TLR-Induced Inflammatory Expression through Modulation of NF-κB p65, JNK, and STAT1."],"pmcid":["PMC9787735"],"funding_grant_id":["116005-3"],"pubmed_authors":["Park HS","Lee S","Park KW","Kang H","Jin SJ","Song Y"],"additional_accession":[]},"is_claimable":false,"name":"Harmine Inhibits Multiple TLR-Induced Inflammatory Expression through Modulation of NF-κB p65, JNK, and STAT1.","description":"Harmine is a beta-carboline alkaloid present in various plants, including in the seeds of <i>Peganum harmala</i> L. This study aimed to investigate the anti-inflammatory activity and mechanism of harmine using macrophages stimulated with various toll-like receptor (TLR) agonists and a model of endotoxemia. The expression of inflammatory mediators induced by ligands of TLRs 2, 3, 4, and 9 were examined in thioglycollate-elicited peritoneal macrophages isolated from BALB/c and C57BL/6 mouse strains. Further, the activation of NF-κB, MAPK, AP-1, and STAT1 was explored using lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (poly(I:C)). Finally, the liver inflammatory response during endotoxemia was examined. Harmine inhibited inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-12, and other markers induced by various TLR agonists. The inhibition of NF-κB activity by harmine occurred via the modulation of p65 phosphorylation, independent of IκBα degradation. The inhibition of AP-1 activity by harmine was associated with the modulation of JNK. Harmine inhibited the LPS-induced serine and tyrosine phosphorylation of STAT1, but only affected serine phosphorylation by poly(I:C) treatment. In vivo, harmine inhibited iNOS and COX-2 expression during endotoxemia. Collectively, the results show that harmine can be effective against infectious inflammation through modulation of NF-κB, JNK, and STAT1.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-22T04:55:16.028Z","creation":"2025-04-05T21:06:07.491Z"},"accession":"S-EPMC9787735","cross_references":{"pubmed":["36556387"],"doi":["10.3390/life12122022"]}}