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Dysregulated inflammation contributes to diseases such as autoimmune disorders and cancer. Interleukin-1 beta (IL-1\u03b2), produced by macrophages in response to lipoteichoic acid (LTA) from Gram-positive bacteria, is a key inflammatory mediator. Glabridin (GBD), a bioactive compound from licorice root, exhibits anti-inflammatory properties. This study investigates GBD\u2019s effects on LTA-induced proinflammatory signaling in RAW 264.7 murine macrophages and alveolar macrophages, MH-S, focusing on IL-1\u03b2 expression and signaling pathways. Cell viability assays confirmed that 20 \u03bcM GBD was non-cytotoxic. Confocal microscopy and quantitative PCR showed that GBD significantly reduced IL-1\u03b2 fluorescence intensity, mRNA, and protein levels. GBD also inhibited inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. Further analysis revealed that GBD suppressed NF-\u03baB p65 nuclear translocation and selectively modulated MAPK pathway activation by reducing JNK and p38 MAPK phosphorylation without affecting ERK. Studies using specific inhibitors demonstrated that IL-1\u03b2 production reduction was mechanistically linked to MAPK pathway inhibition. These findings highlight GBD\u2019s potential as a therapeutic agent for inflammatory diseases through its ability to modulate critical inflammatory mediators and signaling pathways.<\/jats:p>","DOI":"10.3390\/biom15020174","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T08:48:23Z","timestamp":1737708503000},"page":"174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Glabridin Suppresses Macrophage Activation by Lipoteichoic Acid In Vitro: The Crucial Role of MAPKs-IL-1\u03b2-iNOS Axis Signals in Peritoneal and Alveolar Macrophages"],"prefix":"10.3390","volume":"15","author":[{"given":"Shaw-Min","family":"Hou","sequence":"first","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan"},{"name":"Department of Cardiovascular Center, Cathay General Hospital, Taipei 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Neurology, Chi Mei Medical Center, Tainan 710, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Chieh","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9156-0665","authenticated-orcid":false,"given":"Ssu-Wei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1454-0521","authenticated-orcid":false,"given":"Ting-Lin","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Cathay General Hospital, Taipei 106, Taiwan"},{"name":"Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4508-6181","authenticated-orcid":false,"given":"Chih-Wei","family":"Hsia","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Medical University Hospital, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Ying","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hsuan","family":"Hsia","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Translational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fioranelli, M., Roccia, M.G., Flavin, D., and Cota, L. 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