{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T06:03:19Z","timestamp":1780984999598,"version":"3.54.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tranexamic acid (TXA) is a widely used antifibrinolytic agent for the management of hemorrhagic disorders and has increasingly been investigated for the treatment of intracerebral hemorrhage (ICH). However, TXA-associated adverse drug events (ADEs), particularly neurological complications, remain insufficiently characterized, despite their association with unfavorable neurological outcomes, prolonged hospitalization, and increased in-hospital mortality. A systematic evaluation of TXA-related safety risks and underlying mechanisms in ICH is warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      FAERS reports from the first quarter of 2004 to the third quarter of 2023 were analyzed to identify TXA-associated ADE signals using a hierarchical prediction framework integrating statistical learning algorithms. Network toxicology analyses were conducted to explore potential molecular mechanisms and key regulatory targets involved in TXA-related effects in ICH. Drug\u2013target interactions were further assessed by molecular docking and molecular dynamics simulations.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments using ICH-related cell models were performed to validate the predicted neurotoxic effects of TXA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eight significant neurologically related ADE signals associated with TXA were identified, including myoclonic seizures and status epilepticus. Network toxicology analysis highlighted CASP3, PPARA, and BCL2 as key regulatory genes potentially mediating TXA-related neurotoxicity in ICH. Molecular docking demonstrated strong binding affinities between TXA and core targets, with binding energies lower than \u22128.0\u00a0kcal\/mol. Molecular dynamics simulations confirmed stable binding conformations, with root mean square deviation values below 2.0\u00a0\u00c5.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments further supported the potential neurotoxic effects of TXA in ICH cell models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study establishes an integrated computational-to-experimental framework for evaluating the safety of TXA in ICH. The FAERS analysis revealed overall neurological ADE signals for TXA. Combined with network toxicology and\n                      <jats:italic>in vitro<\/jats:italic>\n                      data, these findings suggest potential neurotoxic mechanisms that warrant cautious evaluation in future ICH-specific studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1809788","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:43:01Z","timestamp":1780983781000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational pharmacovigilance of tranexamic acid: implications for intracerebral hemorrhage based on FAERS database and network toxicology"],"prefix":"10.3389","volume":"17","author":[{"given":"Jia-Wei","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Jiangnan University Medical Center","place":["Wuxi, Jiangsu, China"]},{"name":"Wuxi School of Medicine, Jiangnan University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui-Cui","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Acupuncture and Moxibustion, Jiangnan University Medical Center","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Jiangnan University Medical Center","place":["Wuxi, Jiangsu, China"]},{"name":"Department of Neurosurgery, Medical School of Nantong University, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine, Jiangnan University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui-Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Jiangnan University Medical Center","place":["Wuxi, Jiangsu, China"]},{"name":"Department of Neurosurgery, Medical School of Nantong University, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeng-Li","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Jiangnan University Medical Center","place":["Wuxi, Jiangsu, China"]},{"name":"Wuxi School of Medicine, Jiangnan University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-Dong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Jiangnan University Medical Center","place":["Wuxi, Jiangsu, China"]},{"name":"Wuxi School of Medicine, Jiangnan University","place":["Wuxi, Jiangsu, China"]},{"name":"Department of Neurosurgery, Medical School of Nantong University, Nantong University","place":["Nantong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wuxi Ninth People\u2019s Hospital Affiliated to Soochow University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1007\/s11239-020-02141-4","article-title":"National trends in tranexamic acid use in the peripartum period, 2015-2019","volume":"50","author":"Ahmadzia","year":"2020","journal-title":"J. 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