{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:16:11Z","timestamp":1788311771536,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hepatic ischemia\u2013reperfusion injury (HIRI) is a major challenge in liver surgery, and effective pharmacological interventions are lacking. Salvianolic acid C (SaC) has shown protective effects in various pathologies, but its role in HIRI remains unclear. This study investigated whether SaC protects against HIRI and elucidated the underlying mechanisms. Bioinformatics analysis of GSE151648 identified differentially expressed heat shock proteins (HSPs) and associated pathways. Molecular docking predicted SaC binding to HSP90\u03b1 and AKT. A murine HIRI model was established with SaC (10\u2009mg\/kg, i.p.) pretreatment for 7\u2009days. Histology, serum transaminases, and oxidative stress markers assessed liver injury. HSP90\u03b1 inhibition used 17\u2010AAG; in\u00a0vitro hypoxia\/reoxygenation (H\/R) experiments used AML12 hepatocytes. Clinical validation used paired liver tissues from patients undergoing ex\u00a0vivo liver resection and autotransplantation. Twenty\u2010one HSP genes were differentially expressed, with HSP90\u03b1 as a core hub gene in the PI3K\/AKT pathway. SaC showed high binding affinity for HSP90\u03b1 (\u22128.7\u2009kcal\/mol) and p\u2010AKT1 (\u221210.9\u2009kcal\/mol). In mice, SaC upregulated HSP90\u03b1, reduced necrosis and serum transaminases, decreased MDA and increased GSH and SOD, suppressed TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u20106, and reduced apoptosis (Bax\/Bcl\u20102, cleaved caspase\u20103), while activating PI3K\/AKT. These effects were abolished by 17\u2010AAG and confirmed in H\/R\u2010treated AML12 cells. HSP90\u03b1 was also upregulated in post\u2010transplant human livers. SaC protects against HIRI by upregulating HSP90\u03b1 and activating PI3K\/AKT, thereby alleviating oxidative stress, inflammation, apoptosis, and necrosis. These findings support SaC as a potential therapeutic strategy for HIRI.<\/jats:p>","DOI":"10.1002\/ptr.70437","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:00:50Z","timestamp":1788310850000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Salvianolic Acid C Protects Against Hepatic Ischemia\u2013Reperfusion Injury via Heat Shock Protein 90\u03b1\u2010Mediated Activation of the Phosphatidylinositol 3\u2010Kinase\/Protein Kinase B Signaling Pathway"],"prefix":"10.1002","author":[{"given":"Pingping","family":"Qiao","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alimu","family":"Tulahong","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlu","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6582-5773","authenticated-orcid":false,"given":"Tiemin","family":"Jiang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6867-9636","authenticated-orcid":false,"given":"Yanze","family":"Lin","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongdian","family":"Yuan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0891-5307","authenticated-orcid":false,"given":"Rexiati","family":"Ruze","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-345X","authenticated-orcid":false,"given":"Yingmei","family":"Shao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1436973","article-title":"HSP90 Multi\u2010Functionality in Cancer","volume":"15","author":"Albakova Z.","year":"2024","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_14_3_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1093\/ndt\/gft415","article-title":"Intra\u2010Renal Transfection of Heat Shock Protein 90 Alpha or Beta (Hsp90\u03b1 or Hsp90\u03b2) Protects Against Ischemia\/Reperfusion Injury","volume":"29","author":"Barrera\u2010Chimal J.","year":"2014","journal-title":"Nephrology, Dialysis, Transplantation"},{"key":"e_1_2_14_4_1","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s10020-024-00907-7","article-title":"SYK Promotes the Formation of Neutrophil Extracellular Traps by Inducing PKM2 Nuclear Translocation and Promoting STAT3 Phosphorylation to Exacerbate Hepatic Ischemia\u2010Reperfusion Injury and Tumor Recurrence","volume":"30","author":"Chen X.","year":"2024","journal-title":"Molecular Medicine"},{"key":"e_1_2_14_5_1","doi-asserted-by":"crossref","DOI":"10.3390\/antiox10101620","article-title":"Salvianolic Acid C Protects Against Cisplatin\u2010Induced Acute Kidney Injury Through Attenuation of Inflammation, Oxidative Stress and Apoptotic Effects and Activation of the CaMKK\u2010AMPK\u2010Sirt1\u2010Associated Signaling Pathway in Mouse Models","volume":"10","author":"Chien L. 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