{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T17:03:29Z","timestamp":1757610209201,"version":"3.44.0"},"reference-count":28,"publisher":"Aboutscience Srl","issue":"1","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["dti"],"abstract":"<jats:p>Introduction: Bushenhuoxue formula is a traditional Chinese medicine formula with relatively safe clinical effects,but its mechanism in recurrent spontaneous abortion (RSA) is still unclear. Our present study used Network pharmacology an experimental validation to discuss how Bushenhuoxue formula improves prethrombotic state in RSA.Materials and methods: The active ingredients of Bushenhuoxue formula (Drug) were acquired from our previousstudy. The putative targets of ZYP relevant to AS were obtained from TCMSP, Swiss Target Prediction, STITCH,DisGeNET, and Gene Cards databases. Protein-protein interactions (PPI) network, Gene Ontology (GO), and KyotoEncyclopedia of Genes and Genomes (KEGG) analysis were conducted using the Cytoscape software. Furthermore,in vivo experiments were carried out for target validation in BALB\/c mice, collecting placental tissue fromdifferent groups, the cell apoptosis by TUNEL assay; the pathology by HE staining; relative mRNA expression byqRT-PCR assay; relative protein expression by IHC and WB assay.Results: Animal experiments, compared with the NC group, the AT-III, PROG, HCG, APC and t-PA concentrationswere significantly depressed (P\u02c20.05, respectively), Apoptosis cell numbers were significantly up-regulatedwith PI3K\/AKT\/HIF-1\u03b1 VEGF significantly depressing (P\u02c20.001, respectively). With Bushenhuoxue formula supplement, AT-III, PROG, HCG, APC and t-PA concentrations were significantly improved in RSA model mice; andimproved pathological changes and apoptosis cell number in placenta tissues (P\u02c20.05, respectively). However,with LY294002 supplement, the drug treatment effects were disappeared.Conclusion: Bushenhuoxue formula improves prethrombotic state in RSA via stimulating PI3K\/AKT\/HIF-1\u03b1\/VEGFpathway in vivo.<\/jats:p>","DOI":"10.33393\/dti.2025.3562","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T13:58:12Z","timestamp":1756907892000},"page":"59-70","source":"Crossref","is-referenced-by-count":0,"title":["The Bushenhuoxue formula improves prothrombotic state in recurrent spontaneous abortion: network pharmacology and experimental validation"],"prefix":"10.33393","volume":"19","author":[{"given":"Xuan","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8699-3446","authenticated-orcid":false,"given":"Shulan","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maoqing","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinuo","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaqing","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"18642","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"17307","doi-asserted-by":"crossref","unstructured":"Wang F, Jia W, Fan M, et al. Single-cell Immune Landscape of Human Recurrent Miscarriage. Genomics Proteomics Bioinformatics. 2021;19(2):208-222. https:\/\/doi.org\/10.1016\/j.gpb.2020.11.002 PMID:33482359","DOI":"10.1016\/j.gpb.2020.11.002"},{"key":"17308","doi-asserted-by":"crossref","unstructured":"Tian Y, Fu Z, Lan H, et al. Chinese traditional herbs enhanced the clinical efficacy of low-molecular-weight heparin in the treatment of recurrent spontaneous abortion complicated with thrombophilia. Heliyon. 2023;9(2):e13120. https:\/\/doi.org\/10.1016\/j.heliyon.2023.e13120 PMID:36793977","DOI":"10.1016\/j.heliyon.2023.e13120"},{"key":"17309","doi-asserted-by":"crossref","unstructured":"Wang X, Zhao Y, Zhong X. Protective effects of baicalin on decidua cells of LPS-induced mice abortion. J Immunol Res. 2014;2014:859812. https:\/\/doi.org\/10.1155\/2014\/859812 PMID:25386564","DOI":"10.1155\/2014\/859812"},{"key":"17310","doi-asserted-by":"crossref","unstructured":"Lin P, Ji HH, Li YJ, Guo SD. Macrophage Plasticity and Atherosclerosis Therapy. Front Mol Biosci. 2021;8:679797. https:\/\/doi.org\/10.3389\/fmolb.2021.679797 PMID:34026849","DOI":"10.3389\/fmolb.2021.679797"},{"key":"17311","doi-asserted-by":"crossref","unstructured":"Svensson-Arvelund J, Ernerudh J, Buse E, et al. The placenta in toxicology. Part II: systemic and local immune adaptations in pregnancy. Toxicol Pathol. 2014;42(2):327-338. https:\/\/doi.org\/10.1177\/0192623313482205 PMID:23531796","DOI":"10.1177\/0192623313482205"},{"key":"17312","doi-asserted-by":"crossref","unstructured":"Li J, Feng D, He S, Wu Q, Su Z, Ye H. Meta-analysis: association of homocysteine with recurrent spontaneous abortion. Women Health. 2021;61(7):713-720. https:\/\/doi.org\/10.1080\/03630242.2021.1957747 PMID:34334120","DOI":"10.1080\/03630242.2021.1957747"},{"key":"17313","doi-asserted-by":"crossref","unstructured":"Liu Z, Sun S, Xu H, et al. 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