{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:56:01Z","timestamp":1792788961251,"version":"4.5.0"},"reference-count":25,"publisher":"IMR Press","issue":"4","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jiangsu Provincial Association of Chinese Medicine Project","award":["CYTF2024037"],"award-info":[{"award-number":["CYTF2024037"]}]},{"name":"Jiangsu Province Traditional Chinese Medicine Technology Development Project","award":["MS2023037"],"award-info":[{"award-number":["MS2023037"]}]},{"name":"Suzhou Applied Basic Research (Medical and Health) Science and Technology Innovation Project","award":["SYWD2024333"],"award-info":[{"award-number":["SYWD2024333"]}]},{"name":"Medical and Health Project on Suzhou Wuzhong District Science and Technology Plan Youth Project","award":["WZYW2023017"],"award-info":[{"award-number":["WZYW2023017"]}]},{"name":"Applied Basic Research on Special Research of Wumenyipai with Shicaixuepai of Suzhou","award":["SC2023002"],"award-info":[{"award-number":["SC2023002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Sepsis-induced acute lung injury (ALI) poses a significant therapeutic challenge due to the lack of effective treatments. Shionone (SHI), a compound known for its anti-inflammatory properties, was investigated for its potential to mitigate ALI by modulating macrophage polarization, a key process in the inflammatory response. The underlying mechanism was also explored. Methods: We established lipopolysaccharide (LPS)-induced models of ALI in mice and RAW264.7 cells. The protective effects of SHI were assessed in vivo using lung histopathology (hematoxylin and eosin [H&amp;E] staining) and the lung wet-to-dry weight ratio. Cell viability was assessed using a Cell Counting Kit-8 (CCK-8) assay. The levels of inflammatory cytokines (interleukin-6 [IL-6], interleukin-1 beta [IL-1\u03b2], tumor necrosis factor-alpha [TNF-\u03b1], granulocyte-macrophage colony-stimulating factor [GM-CSF], Interleukin-10 [IL-10], transforming growth factor-beta 1 [TGF-\u03b21]) and polarization markers (inducible nitric oxide synthase [iNOS], arginase-1 [Arg1]) were quantified by enzyme-linked immunosorbent assay [ELISA] and real-time quantitative PCR. The expression of key proteins in the high-mobility group box 1 (HMGB1)\/nuclear factor \u03ba B (NF-\u03baB) pathway (HMGB1, toll-like receptor 4 [TLR4], myeloid differentiation primary response 88 [MyD88], NF-\u03baB p65) was analyzed by western blot and immunofluorescence. The study used a small interfering RNA [siRNA] loss-of-function strategy to demonstrate that HMGB1 is a critical target of SHI. Results: SHI treatment significantly attenuated sepsis-induced ALI in mice, as evidenced by improved lung histology, lower lung injury scores, and reduced pulmonary edema. In both in vivo and in vitro models, SHI suppressed the production of pro-inflammatory cytokines (TNF-\u03b1, IL-6, IL-1\u03b2) and the M1 macrophage marker iNOS, while enhancing the release of anti-inflammatory cytokines (GM-CSF, IL-10, TGF-\u03b21) and the M2 marker Arg1. Mechanistically, SHI inhibited the activation of the HMGB1\/NF-\u03baB pathway by downregulating the expression of HMGB1, TLR4, MyD88, and NF-\u03baB phosphorylation. The critical role of HMGB1 was further supported by the finding that siRNA-mediated knockdown of HMGB1 mimicked the anti-inflammatory and polarization-shifting effects induced by SHI. Conclusion: Our findings demonstrate that SHI alleviates sepsis-induced ALI by reprogramming macrophage polarization from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. This protective effect is primarily mediated through the inhibition of the HMGB1\/NF-\u03baB signaling pathway. Thus, SHI represents a potential therapeutic candidate for sepsis-associated lung injury.<\/jats:p>","DOI":"10.31083\/fbl49062","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:29:27Z","timestamp":1777454967000},"source":"Crossref","is-referenced-by-count":1,"title":["Shionone Alleviates Sepsis-Induced Acute Lung Injury by Regulating Macrophage Polarization Through the HMGB1\/NF-\u03baB Pathway"],"prefix":"10.31083","volume":"31","author":[{"given":"Qian","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 215101 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geying","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 215101 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Emergency, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 215101 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junkai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Emergency, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 215101 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 215101 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huojun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 215101 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0128-6149","authenticated-orcid":true,"given":"Biao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 215101 Suzhou, Jiangsu, China"},{"name":"Department of Emergency, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 215101 Suzhou, Jiangsu, China"},{"name":"Department of Central Laboratory, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 215101 Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Barkat MQ, Li Q, Manzoor M, Xu C, Hussain N, Salawi A, et al. 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