{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:10:19Z","timestamp":1792120219268,"version":"4.4.0"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374216"],"award-info":[{"award-number":["82374216"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2025,1]]},"DOI":"10.1016\/j.jep.2024.118937","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T10:01:11Z","timestamp":1729072871000},"page":"118937","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":18,"special_numbering":"P3","title":["Dachaihu decoction alleviates septic intestinal epithelial barrier disruption via PI3K\/AKT pathway based on transcriptomics and network pharmacology"],"prefix":"10.1016","volume":"337","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8440-7013","authenticated-orcid":false,"given":"Na","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxizi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Kao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfeng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingli","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.jep.2024.118937_bib1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1042\/BJ20050959","article-title":"MAPK interacts with occludin and mediates EGF-induced prevention of tight junction disruption by hydrogen peroxide","volume":"393","author":"Basuroy","year":"2005","journal-title":"Biochem. J."},{"issue":"1","key":"10.1016\/j.jep.2024.118937_bib2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41580-020-0278-0","article-title":"Cell fate specification and differentiation in the adult mammalian intestine","volume":"22","author":"Beumer","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.jep.2024.118937_bib3","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2023.116539","article-title":"Preliminary exploration of method for screening efficacy markers compatibility in TCM prescriptions based on Q-markers: anti-inflammatory activity of Dachaihu decoction as an example","volume":"312","author":"Bi","year":"2023","journal-title":"J. Ethnopharmacol."},{"issue":"11","key":"10.1016\/j.jep.2024.118937_bib4","first-page":"2917","article-title":"Exploration on the application of DaChaihu decoction for the treatment of sepsis-related gastrointestinal injury from the perspective of ShaoyangYangming combined syndrome","volume":"40","author":"Chen","year":"2023","journal-title":"J. Guangzhou Univ. Tradit. Chin. Med."},{"issue":"6","key":"10.1016\/j.jep.2024.118937_bib5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/mmr.2021.12480","article-title":"Tong-fu-li-fei decoction attenuates immunosuppression to protect the intestinal-mucosal barrier in sepsis by inhibiting the PD-1\/PD-L1 signaling pathway","volume":"24","author":"Chen","year":"2021","journal-title":"Mol. Med. Rep."},{"issue":"35","key":"10.1016\/j.jep.2024.118937_bib6","first-page":"1","article-title":"Establishment and verification of tight junction model of intestinal epithelial cells","volume":"62","author":"Chen","year":"2022","journal-title":"Shandong Med"},{"issue":"4","key":"10.1016\/j.jep.2024.118937_bib7","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1001\/archsurg.1970.01340280030009","article-title":"Intestinal mucosal lesion in low-flow states: I. A morphological, hemodynamic, and metabolic reappraisal","volume":"101","author":"Chiu","year":"1970","journal-title":"Arch. Surg."},{"issue":"3","key":"10.1016\/j.jep.2024.118937_bib8","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1074\/jbc.M804783200","article-title":"Phosphorylation of tyr-398 and tyr-402 in occludin prevents its interaction with ZO-1 and destabilizes its assembly at the tight junctions","volume":"284","author":"Elias","year":"2009","journal-title":"J. Biol. Chem."},{"issue":"11","key":"10.1016\/j.jep.2024.118937_bib9","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1158\/0008-5472.CAN-03-2904","article-title":"Akt stimulates aerobic glycolysis in cancer cells","volume":"64","author":"Elstrom","year":"2004","journal-title":"Cancer Res."},{"issue":"3","key":"10.1016\/j.jep.2024.118937_bib10","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.apsb.2022.10.016","article-title":"Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice","volume":"13","author":"Fan","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"issue":"2","key":"10.1016\/j.jep.2024.118937_bib11","first-page":"8","article-title":"Expert consensus on gastrointest inal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine","volume":"34","author":"Xudong","year":"2022","journal-title":"Chin. Crit. Care Med."},{"issue":"23","key":"10.1016\/j.jep.2024.118937_bib12","doi-asserted-by":"crossref","DOI":"10.3390\/molecules27238611","article-title":"Development and validation of a UPLC-MS\/MS method for the quantification of components in the ancient classical Chinese medicine formula of guyinjian","volume":"27","author":"Ge","year":"2022","journal-title":"Molecules"},{"issue":"2","key":"10.1016\/j.jep.2024.118937_bib13","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/08923973.2022.2134789","article-title":"SRPK1 promotes sepsis-induced acute lung injury via regulating PI3K\/AKT\/FOXO3 signaling","volume":"45","author":"Guo","year":"2023","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"10.1016\/j.jep.2024.118937_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2023.175930","article-title":"Dapagliflozin ameliorates sepsis-induced heart injury by inhibiting cardiomyocyte apoptosis and electrical remodeling through the PI3K\/Akt pathway","volume":"955","author":"Han","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.jep.2024.118937_bib15","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2020.00376","article-title":"Ferulic acid ameliorates lipopolysaccharide-induced barrier dysfunction via MicroRNA-200c-3p-mediated activation of PI3K\/AKT pathway in caco-2 cells","volume":"11","author":"He","year":"2020","journal-title":"Front. Pharmacol."},{"issue":"1","key":"10.1016\/j.jep.2024.118937_bib16","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s13054-017-1780-4","article-title":"Severity of acute gastrointestinal injury grade is a predictor of all-cause mortality in critically ill patients: a multicenter, prospective, observational study","volume":"21","author":"Hu","year":"2017","journal-title":"Crit. Care"},{"key":"10.1016\/j.jep.2024.118937_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2023.116505","article-title":"Dachaihu decoction ameliorates septic intestinal injury via modulating the gut microbiota and glutathione metabolism as revealed by multi-omics","volume":"312","author":"Huang","year":"2023","journal-title":"J. Ethnopharmacol."},{"issue":"9","key":"10.1016\/j.jep.2024.118937_bib18","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1038\/nprot.2007.303","article-title":"Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers","volume":"2","author":"Hubatsch","year":"2007","journal-title":"Nat. Protoc."},{"issue":"11","key":"10.1016\/j.jep.2024.118937_bib19","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1111\/1440-1681.12649","article-title":"Autophagy in vascular endothelial cells","volume":"43","author":"Jiang","year":"2016","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"issue":"4","key":"10.1016\/j.jep.2024.118937_bib20","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.surg.2023.06.032","article-title":"Targeting sting to reduce sepsis-induced acute intestinal injury","volume":"174","author":"Kobritz","year":"2023","journal-title":"Surgery"},{"issue":"3","key":"10.1016\/j.jep.2024.118937_bib21","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3831\/KPI.2015.18.020","article-title":"Systems biology - a pivotal research methodology for understanding the mechanisms of traditional medicine","volume":"18","author":"Lee","year":"2015","journal-title":"J. Pharmacopuncture"},{"key":"10.1016\/j.jep.2024.118937_bib22","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/1720961","article-title":"Neuregulin-1\u03b2 protects the rat diaphragm during sepsis against oxidative stress and inflammation by activating the PI3K\/akt pathway","volume":"2020","author":"Liu","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"issue":"3","key":"10.1016\/j.jep.2024.118937_bib23","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1017\/S0007114508911612","article-title":"Dietary arginine supplementation alleviates intestinal mucosal disruption induced by Escherichia coli lipopolysaccharide in weaned pigs","volume":"100","author":"Liu","year":"2008","journal-title":"Br. J. Nutr."},{"key":"10.1016\/j.jep.2024.118937_bib24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40635-018-0184-3","article-title":"Body temperature and mouse scoring systems as surrogate markers of death in cecal ligation and puncture sepsis","volume":"6","author":"Mai","year":"2018","journal-title":"Intensive Care Med Exp"},{"issue":"2","key":"10.1016\/j.jep.2024.118937_bib25","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1080\/07391102.2020.1817787","article-title":"Screening of plant-based natural compounds as a potential COVID-19 main protease inhibitor: an in silico docking and molecular dynamics simulation approach","volume":"40","author":"Majumder","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"issue":"7","key":"10.1016\/j.jep.2024.118937_bib26","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.cell.2007.06.009","article-title":"AKT\/PKB signaling: navigating downstream","volume":"129","author":"Manning","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.jep.2024.118937_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2020.113534","article-title":"Gut microbiota modulation and anti-inflammatory properties of Xuanbai Chengqi decoction in septic rats","volume":"267","author":"Mu","year":"2021","journal-title":"J. Ethnopharmacol."},{"issue":"6","key":"10.1016\/j.jep.2024.118937_bib28","doi-asserted-by":"crossref","first-page":"662","DOI":"10.23736\/S0375-9393.20.14302-5","article-title":"The gut as a hidden source of sepsis","volume":"86","author":"Payen","year":"2020","journal-title":"Minerva Anestesiol."},{"issue":"43","key":"10.1016\/j.jep.2024.118937_bib29","doi-asserted-by":"crossref","first-page":"6465","DOI":"10.1038\/sj.onc.1208802","article-title":"PKB\/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP","volume":"24","author":"Porstmann","year":"2005","journal-title":"Oncogene"},{"issue":"4","key":"10.1016\/j.jep.2024.118937_bib30","doi-asserted-by":"crossref","DOI":"10.1186\/cc6958","article-title":"Gastrointestinal Failure score in critically ill patients: a prospective observational study","volume":"12","author":"Reintam","year":"2008","journal-title":"Crit. Care"},{"issue":"10219","key":"10.1016\/j.jep.2024.118937_bib31","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.jep.2024.118937_bib32","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jnutbio.2017.01.013","article-title":"Zinc enhances intestinal epithelial barrier function through the PI3K\/AKT\/mTOR signaling pathway in Caco-2 cells","volume":"43","author":"Shao","year":"2017","journal-title":"J. Nutr. Biochem."},{"issue":"8","key":"10.1016\/j.jep.2024.118937_bib33","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"issue":"1","key":"10.1016\/j.jep.2024.118937_bib34","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1073\/pnas.0802741106","article-title":"PKC\u03b7 regulates occludin phosphorylation and epithelial tight junction integrity","volume":"106","author":"Suzuki","year":"2009","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.1016\/j.jep.2024.118937_bib35","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2023.110049","article-title":"Dl-3-n-butylphthalide improves intestinal microcirculation disorders in septic rats by regulating the PI3K\/AKT signaling pathway and autophagy","volume":"118","author":"Tang","year":"2023","journal-title":"Int. Immunopharmacol."},{"issue":"9","key":"10.1016\/j.jep.2024.118937_bib36","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.3390\/nu15092100","article-title":"Citrulline, intestinal fatty acid-binding protein and the acute gastrointestinal injury score as predictors of gastrointestinal failure in patients with sepsis and septic shock","volume":"15","author":"Tyszko","year":"2023","journal-title":"Nutrients"},{"key":"10.1016\/j.jep.2024.118937_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.prp.2022.153979","article-title":"TSLP protects against sepsis-induced liver injury by inducing autophagy via activation of the PI3K\/Akt\/STAT3 pathway","volume":"236","author":"Wang","year":"2022","journal-title":"Pathol. Res. Pract."},{"issue":"6","key":"10.1016\/j.jep.2024.118937_bib38","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1007\/s10753-019-01085-z","article-title":"Paeoniflorin prevents intestinal barrier disruption and inhibits lipopolysaccharide (LPS)-Induced inflammation in caco-2 cell monolayers","volume":"42","author":"Wu","year":"2019","journal-title":"Inflammation"},{"key":"10.1016\/j.jep.2024.118937_bib39","doi-asserted-by":"crossref","first-page":"525","DOI":"10.3389\/fphar.2018.00525","article-title":"The active components of fuzheng huayu formula and their potential mechanism of action in inhibiting the hepatic stellate cells viability - a network pharmacology and transcriptomics approach","volume":"9","author":"Xing","year":"2018","journal-title":"Front. Pharmacol."},{"issue":"6","key":"10.1016\/j.jep.2024.118937_bib40","doi-asserted-by":"crossref","first-page":"C1231","DOI":"10.1152\/ajpcell.00581.2004","article-title":"Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells","volume":"288","author":"Yu","year":"2005","journal-title":"Am J Physiol Cell Physiol"},{"issue":"4","key":"10.1016\/j.jep.2024.118937_bib41","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.bbrc.2020.10.002","article-title":"ACE2 contributes to the maintenance of mouse epithelial barrier function","volume":"533","author":"Yu","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"4","key":"10.1016\/j.jep.2024.118937_bib42","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1681\/ASN.2016030337","article-title":"Protein kinase c\u03b4 suppresses autophagy to induce kidney cell apoptosis in cisplatin nephrotoxicity","volume":"28","author":"Zhang","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"issue":"7","key":"10.1016\/j.jep.2024.118937_bib43","first-page":"150","article-title":"Effect of Dachaihu Decoction on the level of proinflammatory cytokine levels in the peripheral blood of patients with sepsis","volume":"16","author":"Zhang","year":"2020","journal-title":"Asia-Pacific Tra Med"},{"key":"10.1016\/j.jep.2024.118937_bib44","first-page":"99","article-title":"Clinical study of Dachaihu decoction in the treatment of gastrointestinal dysfunction of sepsis with qi obstruction of fu organs","author":"Zhong","year":"2016","journal-title":"2016 Annual Conference of Chinese Journal of Hospital Pharmacy"}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874124012364?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874124012364?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T15:56:21Z","timestamp":1731340581000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874124012364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":44,"alternative-id":["S0378874124012364"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2024.118937","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Dachaihu decoction alleviates septic intestinal epithelial barrier disruption via PI3K\/AKT pathway based on transcriptomics and network pharmacology","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2024.118937","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118937"}}