{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T23:13:11Z","timestamp":1776121991892,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81173059"],"award-info":[{"award-number":["81173059"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Synergy Engineering Project of Shaanxi Science"},{"name":"Technology Innovation Foundation","award":["2012KTCL03-20"],"award-info":[{"award-number":["2012KTCL03-20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Formononetin, a phytoestrogen, can improve arterial endothelial cell function by upregulating endothelial nitric oxide synthase (eNOS). The estrogen receptor plays an important role in the regulation of eNOS. This study investigated the hypothesis that formononetin upregulates eNOS through estrogen receptors and MAPK pathways.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The rat superior mesenteric arteries were cultured with formononetin or formononetin plus inhibitors for 24 h. The isometric tension of the arteries was measured using a myograph system. The mRNA and protein expression levels of eNOS were determined by real-time PCR and immunohistochemistry, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Acetylcholine (ACh) relaxed the mesenteric arteries precontracted with 5-hydroxytryptamine. This relaxation could be enhanced by formononetin. The removal of endothelium or incubation with l-NAME (a NOS inhibitor) completely abolished the formononetin-enhanced relaxation induced by ACh, suggesting that the formononetin-enhanced vasodilatation is dependent on endothelium and NO pathway. The estrogen receptor inhibitor ICI 182780 attenuated the formononetin-enhanced vasodilatation induced by ACh, suggesting that the formononetin-enhanced arterial relaxation is mediated by the estrogen receptor. Formononetin increased the mRNA and protein expression levels of eNOS. ICI 182780, U0126 (an ERK1\/2 inhibitor) and SP600125 (a JNK inhibitor) prevented the increases in arterial relaxation and eNOS levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Formononetin upregulates eNOS expression in mesenteric arteries via estrogen receptors, ERK1\/2 and JNK pathways.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.12519","type":"journal-article","created":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T10:00:31Z","timestamp":1453284031000},"page":"342-351","source":"Crossref","is-referenced-by-count":17,"title":["Formononetin upregulates nitric oxide synthase in arterial endothelium through estrogen receptors and MAPK pathways"],"prefix":"10.1093","volume":"68","author":[{"given":"Tao","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center , Xi'an, Shaanxi,","place":["China"]},{"name":"Department of Pharmaceutics, Tangdu Hospital, The Fourth Military Medical University , Xi'an, Shaanxi,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center , Xi'an, Shaanxi,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na-Na","family":"Ping","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center , Xi'an, Shaanxi,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Zheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center , Xi'an, Shaanxi,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Xiao","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center , Xi'an, Shaanxi,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,3,1]]},"reference":[{"key":"2024103012562511900_jphp12519-cit-0001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2007.11.002","article-title":"Endothelial dysfunction: a key to the pathophysiology and natural history of peripheral arterial 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