{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:16:49Z","timestamp":1793276209010,"version":"4.5.0"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2023,1]]},"DOI":"10.1016\/j.jep.2022.115746","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T06:47:08Z","timestamp":1664261228000},"page":"115746","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":22,"special_numbering":"C","title":["Mechanism investigation of Shi-Xiao-San in treating blood stasis syndrome based on network pharmacology, molecular docking and in vitro\/vivo pharmacological validation"],"prefix":"10.1016","volume":"301","author":[{"given":"Xing","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingliang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nian","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beihua","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3029-7074","authenticated-orcid":false,"given":"Mingqiu","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peidong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.jep.2022.115746_bib1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"issue":"2","key":"10.1016\/j.jep.2022.115746_bib2","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.joen.2006.11.009","article-title":"Nitric oxide synthase and PGE2 reciprocal interactions in rat dental pulp: cholinoceptor modulation","volume":"33","author":"Borda","year":"2007","journal-title":"J. Endod."},{"key":"10.1016\/j.jep.2022.115746_bib3","doi-asserted-by":"crossref","DOI":"10.1002\/ptr.7396","article-title":"Kaempferol exerts a neuroprotective effect to reduce neuropathic pain through TLR4\/NF-\u0138B signaling pathway","author":"Chang","year":"2022","journal-title":"Phytother Res."},{"key":"10.1016\/j.jep.2022.115746_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2022.153989","article-title":"Mechanisms of Lian-Gui-Ning-Xin-Tang in the treatment of arrhythmia: integrated pharmacology and in vivo pharmacological assessment","volume":"99","author":"Chen","year":"2022","journal-title":"Phytomedicine"},{"key":"10.1016\/j.jep.2022.115746_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2019.103199","article-title":"Biflavones from Ginkgo biloba as inhibitors of human thrombin","volume":"92","author":"Chen","year":"2019","journal-title":"Bioorg. Chem."},{"issue":"W1","key":"10.1016\/j.jep.2022.115746_bib6","doi-asserted-by":"crossref","first-page":"W357","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jep.2022.115746_bib7","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jep.2015.06.030","article-title":"The antithrombotic effect of RSNK in blood-stasis model rats","volume":"173","author":"Dang","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2022.115746_bib8","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13020-019-0253-x","article-title":"Fecal medicines used in traditional medical system of China: a systematic review of their names, original species, traditional uses, and modern investigations","volume":"14","author":"Du","year":"2019","journal-title":"Chin. Med."},{"issue":"22","key":"10.1016\/j.jep.2022.115746_bib9","doi-asserted-by":"crossref","first-page":"5154","DOI":"10.1111\/bph.12834","article-title":"Treatment with LPS plus INF-\u03b3 induces the expression and function of muscarinic acetylcholine receptors, modulating NIH3T3 cell proliferation: participation of NOS and COX","volume":"171","author":"Espa\u00f1ol","year":"2014","journal-title":"Br. J. Pharmacol."},{"issue":"11","key":"10.1016\/j.jep.2022.115746_bib10","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/nrendo.2016.116","article-title":"Fertile ground: human endometrial programming and lessons in health and disease","volume":"12","author":"Evans","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.jep.2022.115746_bib11","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.804327","article-title":"Biphasic effect of pirfenidone on angiogenesis","volume":"12","author":"Gan","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jep.2022.115746_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2020.113591","article-title":"Evaluation of VEGF mediated pro-angiogenic and hemostatic effects and chemical marker investigation for Typhae Pollen and its processed product","volume":"268","author":"Gao","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2022.115746_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2020.113774","article-title":"Effects of carbonized process on quality control, chemical composition and pharmacology of Typhae Pollen: a review","volume":"270","author":"Gao","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2022.115746_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.110301","article-title":"Isorhamnetin: a review of pharmacological effects","volume":"128","author":"Gong","year":"2020","journal-title":"Biomed. Pharmacother."},{"issue":"7494","key":"10.1016\/j.jep.2022.115746_bib15","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature13165","article-title":"Capillary pericytes regulate cerebral blood flow in health and disease","volume":"508","author":"Hall","year":"2014","journal-title":"Nature"},{"issue":"10","key":"10.1016\/j.jep.2022.115746_bib16","doi-asserted-by":"crossref","first-page":"5352","DOI":"10.1002\/ptr.7144","article-title":"Quercetin and metabolic syndrome: a review","volume":"35","author":"Hosseini","year":"2021","journal-title":"Phytother Res."},{"issue":"9","key":"10.1016\/j.jep.2022.115746_bib17","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1111\/j.1745-7254.2005.00164.x","article-title":"Honokiol inhibits arterial thrombosis through endothelial cell protection and stimulation of prostacyclin","volume":"26","author":"Hu","year":"2005","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.jep.2022.115746_bib18","first-page":"75","author":"Hu","year":"2020"},{"issue":"8","key":"10.1016\/j.jep.2022.115746_bib19","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1142\/S0192415X2050086X","article-title":"Progress in traditional Chinese medicine for the treatment of migraine","volume":"48","author":"Huang","year":"2020","journal-title":"Am. J. Chin. Med."},{"key":"10.1016\/j.jep.2022.115746_bib20","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20201981","article-title":"Decoction of heat-clearing, detoxifying and blood stasis removing relieves acute soft tissue injury via modulating MiR-26b-5p\/COX2 Axis to inhibit inflammation","author":"Jiang","year":"2020","journal-title":"Biosci. Rep."},{"key":"10.1016\/j.jep.2022.115746_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiolchem.2020.107402","article-title":"A comprehensive application: molecular docking and network pharmacology for the prediction of bioactive constituents and elucidation of mechanisms of action in component-based Chinese medicine","volume":"90","author":"Jiao","year":"2021","journal-title":"Comput. Biol. Chem."},{"key":"10.1016\/j.jep.2022.115746_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiomed.2021.104562","article-title":"Network pharmacology-based and molecular docking prediction of the active ingredients and mechanism of ZaoRenDiHuang capsules for application in insomnia treatment","volume":"135","author":"Jin","year":"2021","journal-title":"Comput. Biol. Med."},{"issue":"3","key":"10.1016\/j.jep.2022.115746_bib23","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.21037\/apm-21-543","article-title":"Mechanism of Baihe Decoction in the treatment of coronary heart disease based on network pharmacology and molecular docking","volume":"10","author":"Jin","year":"2021","journal-title":"Ann. Palliat. Med."},{"issue":"6","key":"10.1016\/j.jep.2022.115746_bib24","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/aps.2014.139","article-title":"Promoting blood circulation for removing blood stasis therapy for acute intracerebral hemorrhage: a systematic review and meta-analysis","volume":"36","author":"Li","year":"2015","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.jep.2022.115746_bib25","article-title":"Exploring the pharmacological mechanism of radix salvia miltiorrhizae in the treatment of radiation pneumonia by using network pharmacology","volume":"11","author":"Li","year":"2021","journal-title":"Front. Oncol."},{"issue":"2","key":"10.1016\/j.jep.2022.115746_bib26","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.bbrc.2017.06.079","article-title":"Folic acid attenuates cobalt chloride-induced PGE2 production in HUVECs via the NO\/HIF-1 alpha\/COX-2 pathway","volume":"490","author":"Liang","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"5","key":"10.1016\/j.jep.2022.115746_bib27","doi-asserted-by":"crossref","first-page":"e365","DOI":"10.1016\/j.thromres.2010.08.006","article-title":"A series of natural flavonoids as thrombin inhibitors: structure-activity relationships","volume":"126","author":"Liu","year":"2010","journal-title":"Thromb. Res."},{"key":"10.1016\/j.jep.2022.115746_bib28","article-title":"Chinese herb and formulas for promoting blood circulation and removing blood stasis and antiplatelet therapies","author":"Liu","year":"2012","journal-title":"Evid. Based Compl. Alternat."},{"issue":"5","key":"10.1016\/j.jep.2022.115746_bib29","doi-asserted-by":"crossref","first-page":"a020388","DOI":"10.1101\/cshperspect.a020388","article-title":"Astrocyte regulation of blood flow in the brain","volume":"7","author":"MacVicar","year":"2015","journal-title":"Cold Spring Harbor Perspect. Biol."},{"issue":"1","key":"10.1016\/j.jep.2022.115746_bib30","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41467-017-02375-6","article-title":"Hypoxia and hypoxia inducible factor-1\u03b1 are required for normal endometrial repair during menstruation","volume":"23","author":"Maybin","year":"2018","journal-title":"Nat. Commun."},{"issue":"D1","key":"10.1016\/j.jep.2022.115746_bib31","doi-asserted-by":"crossref","first-page":"D877","DOI":"10.1093\/nar\/gkw1012","article-title":"MalaCards: an amalgamated human disease compendium with diverse clinical and genetic annotation and structured search","volume":"45","author":"Rappaport","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jep.2022.115746_bib32","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.brainres.2012.08.036","article-title":"Naringenin and quercetin reverse the effect of hypobaric hypoxia and elicit neuroprotective response in the murine model","volume":"1481","author":"Sarkar","year":"2012","journal-title":"Brain Res."},{"key":"10.1016\/j.jep.2022.115746_bib33","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res. gkac194"},{"issue":"2","key":"10.1016\/j.jep.2022.115746_bib34","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/j.1471-4159.2005.03582.x","article-title":"Polyphenol amentoflavone affords neuroprotection against neonatal hypoxic-ischemic brain damage via multiple mechanisms","volume":"96","author":"Shin","year":"2006","journal-title":"J. Neurochem."},{"issue":"4","key":"10.1016\/j.jep.2022.115746_bib35","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1007\/s10787-021-00827-6","article-title":"Protective effect of (+)-catechin against lipopolysaccharide-induced inflammatory response in RAW 264.7 cells through downregulation of NF-\u03baB and p38 MAPK","volume":"29","author":"Sunil","year":"2021","journal-title":"Inflammopharmacology"},{"issue":"D1","key":"10.1016\/j.jep.2022.115746_bib36","doi-asserted-by":"crossref","first-page":"D380","DOI":"10.1093\/nar\/gkv1277","article-title":"STITCH 5: augmenting protein-chemical interaction networks with tissue and affinity data","volume":"44","author":"Szklarczyk","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jep.2022.115746_bib37","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2021.760918","article-title":"A review on the mechanism and application of keishibukuryogan","volume":"8","author":"Tanaka","year":"2021","journal-title":"Front. Nutr."},{"issue":"9","key":"10.1016\/j.jep.2022.115746_bib38","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.14309\/ajg.0000000000001348","article-title":"Bleeding risk and mortality associated with uninterrupted antithrombotic therapy during percutaneous endoscopic gastrostomy tube placement","volume":"116","author":"Thosani","year":"2021","journal-title":"Am. J. Gastroenterol."},{"issue":"10329","key":"10.1016\/j.jep.2022.115746_bib39","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0140-6736(22)00014-9","article-title":"Safety and efficacy of aspirin, unfractionated heparin, both, or neither during endovascular stroke treatment (MR CLEAN-MED): an open-label, multicentre, randomised controlled trial","volume":"399","author":"van der Steen","year":"2022","journal-title":"Lancet"},{"issue":"2","key":"10.1016\/j.jep.2022.115746_bib40","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0116601","article-title":"Cell-based screening identifies the active ingredients from Traditional Chinese Medicine formula Shixiao San as the inhibitors of atherosclerotic endothelial dysfunction","volume":"10","author":"Wang","year":"2015","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.jep.2022.115746_bib41","first-page":"17","article-title":"Discrimination of aqueous and vinegary extracts of Shixiao San using metabolomics coupled with multivariate data analysis and evaluation of anti-hyperlipidemic effect","volume":"9","author":"Wang","year":"2014","journal-title":"Asian J. Pharm. Sci."},{"issue":"4","key":"10.1016\/j.jep.2022.115746_bib42","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/clpt.2012.96","article-title":"Pharmacogenomics knowledge for personalized medicine","volume":"92","author":"Whirl-Carrillo","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"issue":"6","key":"10.1016\/j.jep.2022.115746_bib43","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1038\/cr.2013.56","article-title":"Hypertensive stretch regulates endothelial exocytosis of Weibel-Palade bodies through VEGF receptor 2 signaling pathways","volume":"23","author":"Xiong","year":"2013","journal-title":"Cell Res."},{"issue":"6","key":"10.1016\/j.jep.2022.115746_bib44","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.apsb.2021.03.024","article-title":"A comprehensive review of integrative pharmacology-based investigation: a paradigm shift in traditional Chinese medicine","volume":"11","author":"Xu","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"issue":"D1","key":"10.1016\/j.jep.2022.115746_bib45","doi-asserted-by":"crossref","first-page":"D976","DOI":"10.1093\/nar\/gky987","article-title":"ETCM: an encyclopaedia of traditional Chinese medicine","volume":"47","author":"Xu","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jep.2022.115746_bib46","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2022.115121","article-title":"Effect of Shixiao San on inflammatory factors and pain in rats with endometriosis","volume":"290","author":"Yue","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2022.115746_bib47","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40199-016-0140-2","article-title":"Comparative Pharmacokinetics of three major bioactive components in rats after oral administration of Typhae Pollen-Trogopterus Feces drug pair before and after compatibility","volume":"24","author":"Zeng","year":"2016","journal-title":"Daru"},{"issue":"1","key":"10.1016\/j.jep.2022.115746_bib48","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jep.2010.04.017","article-title":"Buyang Huanwu decoction ameliorates coronary heart disease with Qi deficiency and blood stasis syndrome by reducing CRP and CD40 in rats","volume":"130","author":"Zhang","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2022.115746_bib49","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jchromb.2017.12.035","article-title":"Urinary metabolomics study the mechanism of Taohong Siwu Decoction intervention in acute blood stasis model rats based on liquid chromatography coupled to quadrupole time-of-flight mass spectrometry","volume":"1074\u20131075","author":"Zhang","year":"2018","journal-title":"J. Chromatogr., B: Anal. Technol. Biomed. Life Sci."},{"key":"10.1016\/j.jep.2022.115746_bib50","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2020.104963","article-title":"Interactions of antithrombotic herbal medicines with Western cardiovascular drugs","volume":"159","author":"Zuo","year":"2020","journal-title":"Pharmacol. Res."}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874122007851?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874122007851?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:29:55Z","timestamp":1759944595000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874122007851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":50,"alternative-id":["S0378874122007851"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2022.115746","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mechanism investigation of Shi-Xiao-San in treating blood stasis syndrome based on network pharmacology, molecular docking and in vitro\/vivo pharmacological validation","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2022.115746","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"115746"}}