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Astragaloside IV (AS\u2010IV), a glycoside extracted from <jats:italic>Astragalus membranaceus Bunge<\/jats:italic>, has been shown to inhibit Ang II\u2013induced inflammatory responses in vivo. However, the mechanisms underlying the beneficial effects are still unclear. This study investigated whether AS\u2010IV attenuates endothelial inflammation induced by Ang II via the activation of endothelial nitric oxide synthase (eNOS)\/nitric oxide (NO) pathway. Human umbilical vein endothelial cells (HUVECs) were cultured in the presence of AS\u2010IV with or without the specific inhibitor of NOS or Ca<jats:sup>2+<\/jats:sup>\u2010 and phosphatidylinositol 3\u2010kinase (PI3K)\/Akt\u2010dependent cascade prior to Ang II exposure. Incubation of HUVECs with AS\u2010IV enhanced NO production and eNOS<jats:sup>ser1177<\/jats:sup> phosphorylation. These responses were abrogated by the inhibition of NOS or Ca<jats:sup>2+<\/jats:sup>\u2010 and PI3K\/Akt\u2010dependent pathway. In addition, preincubation of HUVECs with AS\u2010IV inhibited Ang II\u2013induced cytokine and chemokine production, adhesion molecule expression, monocyte adhesion, and nuclear factor kappa B (NF\u2010\u03baB) activation as evidenced by the attenuation of inhibitor of kappa B alpha phosphorylation and subsequent NF\u2010\u03baB DNA binding. These effects of AS\u2010IV were abolished by the suppression of NOS or Ca<jats:sup>2+<\/jats:sup>\u2010 and PI3K\/Akt\u2010dependent cascade. Our findings indicate that AS\u2010IV attenuates inflammatory responses triggered by Ang II possibly via the activation of Ca<jats:sup>2+<\/jats:sup>\/PI3K\/Akt\/eNOS\/NO pathway in endothelial cells.<\/jats:p>","DOI":"10.1155\/2024\/3193950","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T13:49:40Z","timestamp":1730296180000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Role of Ca<sup>2+<\/sup>\/PI3K\/Akt\/eNOS\/NO Pathway in Astragaloside IV\u2013Induced Inhibition of Endothelial Inflammation Triggered by Angiotensin II"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7421-224X","authenticated-orcid":false,"given":"Shiyu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7958-280X","authenticated-orcid":false,"given":"Shijie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7019-040X","authenticated-orcid":false,"given":"Shiyang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8533-2659","authenticated-orcid":false,"given":"Lin","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4215-2307","authenticated-orcid":false,"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1421-8564","authenticated-orcid":false,"given":"Youping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7092151"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0003319720987752"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2022.04.011"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9070781"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11142229"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00038.2017"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.13228"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20133294"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2017.03.016"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2020.115809"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12232"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apha.2019.08.002"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2016.11.006"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00496"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9542165"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104831"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-017-0313-2"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-019-2728-9"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612826666200318152049"},{"key":"e_1_2_13_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13517"},{"key":"e_1_2_13_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-021-09785-7"},{"key":"e_1_2_13_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2019.11.004"},{"key":"e_1_2_13_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.118.311282"},{"key":"e_1_2_13_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11040616"},{"key":"e_1_2_13_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaa070"},{"key":"e_1_2_13_26_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2021.0027"},{"key":"e_1_2_13_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.014232"},{"key":"e_1_2_13_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26154533"},{"key":"e_1_2_13_29_2","first-page":"469","article-title":"Nitric Oxide and Superoxide in Inflammation and Immune Regulation","volume":"54","author":"Guzik T. 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