{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:41:56Z","timestamp":1777502516635,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"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":["NRF-2014M3A9D5A01073841"],"award-info":[{"award-number":["NRF-2014M3A9D5A01073841"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021M3A9I4023974"],"award-info":[{"award-number":["NRF-2021M3A9I4023974"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1I1A3042761"],"award-info":[{"award-number":["NRF-2021R1I1A3042761"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1A6A1A11036849"],"award-info":[{"award-number":["NRF-2019R1A6A1A11036849"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The herbal plant Angelica gigas (A. gigas) has been used in traditional medicine in East Asian countries, and its chemical components are reported to have many pharmacological effects. In this study, we showed that a bioactive ingredient of A. gigas modulates the functional activity of macrophages and investigated its effect on inflammation using a sepsis model. Among 12 different compounds derived from A. gigas, decursinol angelate (DA) was identified as the most effective in suppressing the induction of TNF-\u03b1 and IL-6 in murine macrophages. When mice were infected with a lethal dose of methicillin-resistant Staphylococcus aureus (MRSA), DA treatment improved the mortality and bacteremia, and attenuated the cytokine storm, which was associated with decreased CD38+ macrophage populations in the blood and liver. In vitro studies revealed that DA inhibited the functional activation of macrophages in the expression of pro-inflammatory mediators in response to microbial infection, while promoting the bacterial killing ability with an increased production of reactive oxygen species. Mechanistically, DA treatment attenuated the NF-\u03baB and Akt signaling pathways. Intriguingly, ectopic expression of an active mutant of IKK2 released the inhibition of TNF-\u03b1 production by the DA treatment, whereas the inhibition of Akt resulted in enhanced ROS production. Taken together, our experimental evidence demonstrated that DA modulates the functional activities of pro-inflammatory macrophages and that DA could be a potential therapeutic agent in the management of sepsis.<\/jats:p>","DOI":"10.3390\/ijms222010950","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T09:16:42Z","timestamp":1633943802000},"page":"10950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Decursinol Angelate Mitigates Sepsis Induced by Methicillin-Resistant Staphylococcus aureus Infection by Modulating the Inflammatory Responses of Macrophages"],"prefix":"10.3390","volume":"22","author":[{"given":"Seongwon","family":"Pak","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bikash","family":"Thapa","sequence":"additional","affiliation":[{"name":"Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keunwook","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Hallym University, Chuncheon 24252, Korea"},{"name":"Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.5483\/BMBRep.2019.52.6.140","article-title":"Metabolic influence on macrophage polarization and pathogenesis","volume":"52","author":"Thapa","year":"2019","journal-title":"BMB Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/j.1365-2567.2007.02719.x","article-title":"Immunological decision-making: How does the immune system decide to mount a helper T-cell response?","volume":"123","author":"Kaiko","year":"2008","journal-title":"Immunology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nri978","article-title":"Alternative activation of macrophages","volume":"3","author":"Gordon","year":"2003","journal-title":"Nat. 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