{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:19:58Z","timestamp":1790302798304,"version":"4.1.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"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. Pharmacol."],"abstract":"<jats:p>\n                    Ganoderic acid A (GAA), a major bioactive triterpenoid from Ganoderma lucidum, is known for its anti-inflammatory effects; however, its precise molecular targets in sepsis-related liver injury (SRLI) remain unclear. Integrating network pharmacology and transcriptomic analysis, we identified Tumor Necrosis Factor-alpha (TNF\u03b1) as a primary candidate target. Subsequent biophysical validation using surface plasmon resonance (SPR) and molecular dynamics (MD) simulations confirmed that GAA directly binds to TNF\u03b1. Functionally, this interaction inhibits the TNF\u03b1\/NF-\u03baB signaling axis, thereby suppressing macrophage M1 polarization and ameliorating liver injury\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . This study identifies TNF\u03b1 as a primary candidate target of GAA, providing a mechanistic basis for its hepatoprotective effects and therapeutic potential.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1754172","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T10:59:20Z","timestamp":1769425160000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Multi-omics integration identifies ganoderic acid A as a TNF\u03b1 inhibitor for treating sepsis-related liver injury"],"prefix":"10.3389","volume":"17","author":[{"given":"Hong","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zike","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"107823","DOI":"10.1016\/j.intimp.2021.107823","article-title":"Anti-inflammatory and M2 macrophage polarization-promoting effect of mesenchymal stem cell-derived exosomes","volume":"97","author":"Arabpour","year":"2021","journal-title":"Int. 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