{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:58:50Z","timestamp":1785405530077,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["NJH #1146128"],"award-info":[{"award-number":["NJH #1146128"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["TJKL #1159261"],"award-info":[{"award-number":["TJKL #1159261"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"award":["NJH #1146128"],"award-info":[{"award-number":["NJH #1146128"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TJKL #1159261"],"award-info":[{"award-number":["TJKL #1159261"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Preeclampsia is a serious pregnancy complication characterised by maternal vascular dysfunction, placental dysfunction, and organ injury, with no effective treatment currently available. Kampo, a system of Japanese traditional medicine comprising standardised herbal formulations, could target pathophysiological pathways driving preeclampsia. We evaluated the effects of select Kampo formulations on markers of preeclampsia using primary human trophoblasts, placental explants, human umbilical vein endothelial cells (HUVECs), and uterine microvascular endothelial cells (UtMVECs). Twelve formulations were initially screened in HUVECs, and six formulations advanced for further study. TNF\u03b1 was used to induce endothelial dysfunction, and angiogenic, antioxidant, inflammatory, and vascular dysfunction markers were assessed. Overall, Kampo formulations had minimal effect on sFlt-1 expression and only modest effects on sFlt-1 secretion by primary human trophoblast. In contrast, several formulations consistently increased placental growth factor (PlGF) expression and secretion, upregulated HMOX1 in trophoblasts, and enhanced PlGF secretion from placental explants. In endothelial cells, Kampo treatment partially reversed TNF\u03b1-induced dysfunction, demonstrated by reduced VCAM1 expression, and additional endothelial cell type-dependent effects on ET-1 and inflammatory pathways. These findings indicate that selected Kampo formulations modulate key pathways involved in the pathophysiology underpinning preeclampsia and warrant further investigation as potential therapeutic candidates.<\/jats:p>","DOI":"10.3390\/antiox15070877","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T03:06:52Z","timestamp":1784084812000},"page":"877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Kampo Medicines Modulate Angiogenic, Antioxidant, and Inflammatory Pathways in Human Preclinical Models: Implications for Preeclampsia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8943-2269","authenticated-orcid":false,"given":"Natalie K.","family":"Binder","sequence":"first","affiliation":[{"name":"Therapeutic Discovery and Vascular Function in Pregnancy Group, University of Melbourne and Mercy Hospital for Women, Heidelberg 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Onda","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2322-0471","authenticated-orcid":false,"given":"Sally","family":"Beard","sequence":"additional","affiliation":[{"name":"Therapeutic Discovery and Vascular Function in Pregnancy Group, University of Melbourne and Mercy Hospital for Women, Heidelberg 3084, Australia"},{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Uchiyama","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chika","family":"Ohi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8376-0096","authenticated-orcid":false,"given":"Natasha","family":"de Alwis","sequence":"additional","affiliation":[{"name":"Therapeutic Discovery and Vascular Function in Pregnancy Group, University of Melbourne and Mercy Hospital for Women, Heidelberg 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Baird","sequence":"additional","affiliation":[{"name":"Therapeutic Discovery and Vascular Function in Pregnancy Group, University of Melbourne and Mercy Hospital for Women, Heidelberg 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tu\u2019uhevaha J.","family":"Kaitu\u2019u-Lino","sequence":"additional","affiliation":[{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg 3084, Australia"},{"name":"Translational Obstetrics Group, University of Melbourne and Mercy Hospital for Women, Heidelberg 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Kampo Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Ohu University, Koriyama 963-8611, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie J.","family":"Hannan","sequence":"additional","affiliation":[{"name":"Therapeutic Discovery and Vascular Function in Pregnancy Group, University of Melbourne and Mercy Hospital for Women, Heidelberg 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2020). 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