{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T12:36:12Z","timestamp":1763987772094,"version":"3.41.2"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T00:00:00Z","timestamp":1479859200000},"content-version":"vor","delay-in-days":327,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC-81403139-H2809"],"award-info":[{"award-number":["NSFC-81403139-H2809"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>Calycosin and formononetin are two structurally similar isoflavonoids that have been shown to induce vasodilation in aorta and conduit arteries, but study of their actions on endothelial functions is lacking. Here, we demonstrated that both isoflavonoids relaxed rat mesenteric resistance arteries in a concentration\u2010dependent manner, which was reduced by endothelial disruption and nitric oxide synthase (NOS) inhibition, indicating the involvement of both endothelium and vascular smooth muscle. In addition, the endothelium\u2010dependent vasodilation, but not the endothelium\u2010independent vasodilation, was blocked by BK<jats:sub>Ca<\/jats:sub> inhibitor iberiotoxin (IbTX). Using human umbilical vein endothelial cells (HUVECs) as a model, we showed calycosin and formononetin induced dose\u2010dependent outwardly rectifying K<jats:sup>+<\/jats:sup> currents using whole cell patch clamp. These currents were blocked by tetraethylammonium chloride (TEACl), charybdotoxin (ChTX), or IbTX, but not apamin. We further demonstrated that both isoflavonoids significantly increased nitric oxide (NO) production and upregulated the activities and expressions of endothelial NOS (eNOS) and neuronal NOS (nNOS). These results suggested that calycosin and formononetin act as endothelial BK<jats:sub>Ca<\/jats:sub> activators for mediating endothelium\u2010dependent vasodilation through enhancing endothelium hyperpolarization and NO production. Since activation of BK<jats:sub>Ca<\/jats:sub> plays a role in improving behavioral and cognitive disorders, we suggested that these two isoflavonoids could provide beneficial effects to cognitive disorders through vascular regulation.<\/jats:p>","DOI":"10.1155\/2016\/5272531","type":"journal-article","created":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T21:08:46Z","timestamp":1479935326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Calycosin and Formononetin Induce Endothelium\u2010Dependent Vasodilation by the Activation of Large\u2010Conductance Ca<sup>2+<\/sup>\u2010Activated K<sup>+<\/sup> Channels (BK<sub>Ca<\/sub>)"],"prefix":"10.1155","volume":"2016","author":[{"given":"Hisa Hui Ling","family":"Tseng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi Teng","family":"Vong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George Pak-Heng","family":"Leung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai Wang","family":"Seto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9024-1275","authenticated-orcid":false,"given":"Yiu Wa","family":"Kwan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon Ming-Yuen","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2630-3707","authenticated-orcid":false,"given":"Maggie Pui Man","family":"Hoi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,23]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_9_1_2","DOI":"10.1002\/ptr.2332"},{"key":"e_1_2_9_2_2","first-page":"422","article-title":"Botanical influences on cardiovascular disease","volume":"3","author":"Miller A. 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