{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:56:14Z","timestamp":1790963774154,"version":"4.1.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Pregnancy-induced Hypertension (PIH) is a disease that causes serious maternal and fetal morbidity and mortality. Alisma Orientale (AO) has a long history of use as traditional Chinese medicine therapy for PIH. This study explores its potential mechanism and biosafety based on network pharmacology, network toxicology, molecular docking and molecular dynamics simulation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Compounds of AO were screened in TCMSP, TCM-ID, TCM@Taiwan, BATMAN, TOXNET and CTD database; PharmMapper and SwissTargetPrediction, GeneCards, DisGeNET and OMIM databases were used to predict the targets of AO anti-PIH. The protein-protein interaction analysis and the KEGG\/GO enrichment analysis were applied by STRING and Metascape databases, respectively. Then, we constructed the \u201cherb-compound-target-pathway-disease\u201d map in Cytoscape software to show the core regulatory network. Finally, molecular docking and molecular dynamics simulation were applied to analyze binding affinity and reliability. The same procedure was conducted for network toxicology to illustrate the mechanisms of AO hepatotoxicity and nephrotoxicity.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    29 compounds with 78 potential targets associated with the therapeutic effect of AO on PIH, 10 compounds with 117 and 111 targets associated with AO induced hepatotoxicity and nephrotoxicity were obtained, respectively. The PPI network analysis showed that core therapeutic targets were IGF, MAPK1, AKT1 and EGFR, while PPARG and TNF were toxicity-related targets. Besides, GO\/KEGG enrichment analysis showed that AO might modulate the PI3K-AKT and MAPK pathways in treating PIH and mainly interfere with the lipid and atherosclerosis pathways to induce liver and kidney injury. The \u201cherb-compound-target-pathway-disease\u201d network showed that triterpenoids were the main therapeutic compounds, such as Alisol B 23-Acetate and Alisol C, while emodin was the main toxic compounds. The results of molecular docking and molecular dynamics simulation also showed good binding affinity between core compounds and targets.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    This research illustrated the mechanism underlying the therapeutic effects of AO against PIH and AO induced hepato-nephrotoxicity. However, further experimental verification is warranted for optimal use of AO during clinical practice.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.1027112","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T02:19:55Z","timestamp":1668478795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":41,"title":["Exploring the mechanism of Alisma orientale for the treatment of pregnancy induced hypertension and potential hepato-nephrotoxicity by using network pharmacology, network toxicology, molecular docking and molecular dynamics simulation"],"prefix":"10.3389","volume":"13","author":[{"given":"Yilin","family":"Liao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1161\/HYPERTENSIONAHA.122.18920","article-title":"Role of antihypertensive treatment and blood pressure control in the occurrence of adverse pregnancy outcomes: A population-based study of linked electronic health records","volume":"79","author":"Al Khalaf","year":"2022","journal-title":"Hypertension"},{"key":"B2","doi-asserted-by":"publisher","first-page":"5881","DOI":"10.1074\/jbc.M114.624759","article-title":"Tumor necrosis factor (TNF)-\u03b1-induced repression of GKAP42 protein levels through cGMP-dependent kinase (cGK)-I\u03b1 causes insulin resistance in 3T3-L1 adipocytes","volume":"290","author":"Ando","year":"2015","journal-title":"J. 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