{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:16:31Z","timestamp":1792106191849,"version":"4.4.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2021-NR058556 RS-2024-00344154 RS-2021-NR056525 RS-2021-NR060131"],"award-info":[{"award-number":["RS-2021-NR058556 RS-2024-00344154 RS-2021-NR056525 RS-2021-NR060131"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Pogostemon stellatus<\/jats:italic> (Lour.) Kuntze is a plant native to South and East Asia belonging to the Lamiaceae family, whose members are widely recognized for their anti-inflammatory and antioxidant properties. However, these properties have not been extensively studied in <jats:italic>P. stellatus<\/jats:italic> (Lour.) Kuntze. This study aimed to evaluate the anti-inflammatory and antioxidant effects of methanol extract of <jats:italic>P. stellatus<\/jats:italic> (Lour.) Kuntze (MPSK) in LPS-stimulated RAW 264.7 macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RAW 264.7 macrophages were stimulated with LPS and treated with MPSK. Anti-inflammatory effects were assessed by measuring nitric oxide (NO) and prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) levels and the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), interleukin-1\u03b2 (IL-1\u03b2), and tumor necrosis factor-\u03b1 (TNF-\u03b1) at both mRNA and protein levels. Nuclear factor-\u03baB (NF-\u03baB) and mitogen-activated protein kinase (MAPK) pathway involvement was examined. Antioxidant capacity was determined using a DPPH radical scavenging assay, and nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MPSK markedly attenuated the production of inflammatory mediators and cytokines in LPS-induced RAW 264.7 macrophages. NO production was suppressed by 98%, compared with the LPS-treated group. PGE<jats:sub>2<\/jats:sub> production was also inhibited by 64%. Consistent with these findings, MPSK significantly reduced the protein and mRNA expression levels of iNOS and COX-2. Furthermore, MPSK suppressed the production and expression of pro-inflammatory cytokines, including IL-1\u03b2, IL-6, and TNF-\u03b1. Notably, when MPSK was administered at 100\u00a0\u03bcg\/mL, IL-6 and IL-1\u03b2 production were reduced by 21% and 18%, respectively, compared with the LPS-treated group. These anti-inflammatory effects were associated with the inhibition of NF-\u03baB and MAPK signaling pathways. Immunoblot analysis demonstrated that NF-\u03baB protein expression was reduced by 72% upon treatment with MPSK, while the phosphorylation of ERK, JNK, and p38 was suppressed by 38%, 56%, and 35%, respectively. MPSK suppressed ROS levels in RAW 264.7 cells by 62%, demonstrating its potent antioxidant capacity. This antioxidant activity of MPSK was demonstrated by the upregulation of Nrf2 and its downstream antioxidant target genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MPSK possesses both anti-inflammatory and antioxidant activities through regulation of NF-\u03baB, MAPK, and Nrf2 pathways, suggesting its potential as a therapeutic agent against inflammation and oxidative stress.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1679919","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T05:30:48Z","timestamp":1758778248000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Anti-inflammatory and antioxidant effects of Pogostemon stellatus (Lour.) Kuntze via MAPK, NF-\u03baB, and Nrf2 signaling pathways in LPS-activated RAW 264.7 macrophages"],"prefix":"10.3389","volume":"16","author":[{"given":"Haelim","family":"Yoon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You Li","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihye","family":"Seo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyu","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. 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