{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T04:46:03Z","timestamp":1782708363538,"version":"3.54.5"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis-induced acute lung injury (ALI) represents the earliest and most severe complication of sepsis, with extraordinarily high mortality rates. Baihe Gujin decoction (BHGJD), a classical traditional Chinese medicine formula, has demonstrated protective effects against various pulmonary diseases, yet its therapeutic potential in sepsis-induced ALI remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The chemical constituents of BHGJD were characterized by mass spectrometry, and potential protective mechanisms were predicted using network pharmacology.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , a cecal ligation and puncture (CLP) mouse model was established to evaluate BHGJD\u2019s protective effects through histopathological assessment and serum inflammatory cytokine analysis. Lung tissue RNA sequencing and untargeted metabolomics were performed to explore underlying molecular mechanisms, followed by validation of key proteins (HO-1, GPX4, PPAR\u03b1, CPT1A, mTOR, and p-mTOR) by Western blot, immunohistochemistry, and immunofluorescence. Lung-deposited bioactive components were subsequently identified by mass spectrometry.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , (+)-catechin, a representative lung-exposed constituent detected in lung tissue, was used to treat lipopolysaccharide-induced MLE-12 cells. Cellular levels of adenosine triphosphate, reactive oxygen species, and ferrous iron were measured. Mitochondrial ultrastructure was assessed by transmission electron microscopy, and fatty acid oxidation capacity was evaluated using the Seahorse palmitate oxidation assay, followed by validation of key proteins by Western blot.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BHGJD significantly ameliorated CLP-induced ALI, as evidenced by improved histological architecture and reduced inflammatory cytokine levels. Integrated multi-omics analysis and experimental validation revealed three interconnected protective mechanisms: 1) activation of an Nrf2\/GPX4-associated antioxidant response, initially suggested by glutathione pathway enrichment, reduced lipid peroxidation-related metabolites, and restoration of redox and mitochondrial homeostasis; 2) PPAR\u03b1\/CPT1A-associated metabolic remodeling toward fatty acid utilization, supported by fatty acid transport\/metabolism enrichment, coordinated changes in multiple acylcarnitine species, increased PPAR\u03b1\/CPT1A expression, and improved palmitate-supported mitochondrial respiration\n                      <jats:italic>in vitro<\/jats:italic>\n                      ; and 3) reduction of inflammatory lipid mediators. Altered mTOR signaling accompanied these changes and may represent a convergent regulatory pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BHGJD alleviates sepsis-induced ALI through coordinated enhancement of Nrf2\/GPX4-associated antioxidant defense, PPAR\u03b1\/CPT1A-linked metabolic reprogramming toward fatty acid utilization, and suppression of inflammatory lipid mediators. These findings provide an integrated mechanistic framework for the protective actions of BHGJD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1767881","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T04:26:40Z","timestamp":1782707200000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Baihe Gujin decoction ameliorates sepsis-induced acute lung injury through Nrf2\/GPX4-mediated antioxidant defense and PPAR\u03b1-driven metabolic reprogramming: a multi-omics investigation"],"prefix":"10.3389","volume":"17","author":[{"given":"Kaiyuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital","place":["Shanghai, China"]},{"name":"Department of Traditional Chinese Medicine, Loujiang New City Hospital of Taicang (Taicang Branch of Ruijin 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