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Baicalein (Bai) is one of the major active components of\n                    <jats:italic>Scutellariae Radix<\/jats:italic>\n                    for treating pulmonary diseases. However, its specific underlying molecular mechanism is unknown for treating sepsis\u2010mediated ALI. Herein, we found that Bai inhibited the nuclear factor kappa B (NF\u2010\u03baB) pathway to suppress inflammation and oxidative stress in vitro and in vivo, alleviating the course of lung injury. Affinity chromatography revealed that Bai directly bound to eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) through hydrogen bond interaction with Q108 and D110, exhibiting a dissociation constant (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    ) of 336\u00a0nM. Mechanistically, Bai blocked the interaction between eEF1A1 and peroxiredoxin 4 (Prdx4) to inhibit ring finger protein 14 (RNF14)\u2010mediated ubiquitin\u2010dependent degradation of Prdx4 based on APEX2 and Co\u2010IP experiments. Moreover, eEF1A1 knockdown could repress inflammation, whereas its overexpression exerted an opposite effect in the in vitro experiments. Notably, Bai did not display any\u00a0additional protective effect in LPS\u2010mediated eEF1A1 knockdown cells, while its effect was weakened in LPS\u2010mediated eEF1A1 overexpression cells. In addition, our study revealed that the course of sepsis\u2010mediated lung injury was alleviated in vivo by eEF1A1 knockdown, and no extra effects were exhibited by Bai in sepsis\u2010mediated eEF1A1 knockdown mice. These findings collectively suggested that targeting eEF1A1 represented a promising therapeutic strategy against sepsis\u2010associated lung injury through dual anti\u2010inflammatory and antioxidant mechanisms, particularly via Bai's role as a direct blocker disrupting eEF1A1\u2010Prdx4 interactions.\n                  <\/jats:p>","DOI":"10.1002\/exp2.70206","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T03:48:13Z","timestamp":1787629693000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting eEF1A1 With Baicalein to Block eEF1A1\/Prdx4 Interaction for Treating Sepsis\u2010Mediated Lung Injury"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9501-2103","authenticated-orcid":false,"given":"Jing","family":"Chang","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, School of Medical Technology, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1960-6621","authenticated-orcid":false,"given":"Hui\u2010Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, School of Medical Technology, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi\u2010Meng","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, School of Medical Technology, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Wen","family":"Hui","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, School of Medical Technology, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Rong","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, School of Medical Technology, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0439-6466","authenticated-orcid":false,"given":"Mahmood Brobbey","family":"Oppong","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry School of Pharmacy, College of Health Sciences University of Ghana  Accra Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Li","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, School of Medical Technology, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, School of Medical Technology, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6801-3439","authenticated-orcid":false,"given":"Cheng\u2010Peng","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, School of Medical Technology, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-8670","authenticated-orcid":false,"given":"Feng","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, School of Medical Technology, Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of 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