{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:50:10Z","timestamp":1792792210925,"version":"4.5.0"},"reference-count":89,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"crossref","award":["23JRRA0970"],"award-info":[{"award-number":["23JRRA0970"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Education Development Fund of Lanzhou University","award":["071100149"],"award-info":[{"award-number":["071100149"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Artemether, a derivative of the natural compound artemisinin, is increasingly recognized for its multi-target anti-inflammatory and antioxidant properties. This review systematically elucidates the molecular mechanisms underlying these effects, focusing on artemether\u2019s dual modulation of the MAPK\/NF-\u03baB and Nrf2 signaling pathways. We detail how artemether concurrently inhibits the MAPK\/NF-\u03baB axis\u2014suppressing IKK\u03b2 phosphorylation and I\u03baB\u03b1 degradation to block NF-\u03baB nuclear translocation\u2014and downregulates p38\/contextually modulates ERK phosphorylation. This leads to a significant reduction in key inflammatory mediators, including TNF-\u03b1, IL-6, and COX-2. Simultaneously, artemether activates the Nrf2 antioxidant pathway, upregulating HO-1 expression and enhancing the activity of SOD and GSH-Px, which effectively scavenges free radicals and reduces markers of oxidative damage such as MDA and 8-OHdG. The core therapeutic synergy arises from artemether\u2019s disruption of the ROS-NF-\u03baB positive feedback loop, which inhibits neutrophil infiltration and lipid peroxidation, thereby ameliorating tissue injury in experimental models of arthritis and neurodegenerative diseases. Compared to conventional NSAIDs and glucocorticoids, artemether exhibits a favorable safety profile, particularly regarding gastrointestinal effects, and demonstrates unique immunomodulatory potential. Future research directions should prioritize the development of nano-targeted delivery systems and the elucidation of pathway crosstalk at the single-cell level to advance the clinical translation of artemether for chronic inflammatory diseases.<\/jats:p>","DOI":"10.3390\/ijms27104607","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:06:07Z","timestamp":1779365167000},"page":"4607","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Research Progress on Anti-Inflammatory and Antioxidant Mechanism of Artemether Based on MAPK\/NF-\u03baB Signaling Pathway"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1490-1787","authenticated-orcid":false,"given":"Mingxuan","family":"Yang","sequence":"first","affiliation":[{"name":"Clinical Medical School, Lanzhou University, Lanzhou 730000, China"},{"name":"The College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Feng","sequence":"additional","affiliation":[{"name":"Clinical Medical School, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Medical School, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Clinical Medical School, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanwei","family":"Ma","sequence":"additional","affiliation":[{"name":"Clinical Medical School, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijun","family":"Feng","sequence":"additional","affiliation":[{"name":"Clinical Medical School, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2015). 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