{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T19:58:12Z","timestamp":1740167892619,"version":"3.37.3"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T00:00:00Z","timestamp":1500336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Eupatilin (5,7\u2010dihydroxy\u20103,4,6\u2010trimethoxyflavone) is one of the main compounds present in <jats:italic>Artemisia<\/jats:italic> species. Eupatilin has both antioxidative and anti\u2010inflammatory properties and a relaxation effect on vascular contraction regardless of endothelial function. We evaluated the relaxant effects of eupatilin on the corpus cavernosum (<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>) of rabbits and the underlying mechanisms of its activity in human corpus cavernosum smooth muscle (<jats:styled-content style=\"fixed-case\">CCSM<\/jats:styled-content>) cells. Isolated rabbit <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content> strips were mounted in an organ bath system. A conventional whole\u2010cell patch clamp technique was used to measure activation of calcium\u2010sensitive K<jats:sup>+<\/jats:sup>\u2010channel currents in human <jats:styled-content style=\"fixed-case\">CCSM<\/jats:styled-content> cells. The relaxation effect of eupatilin was evaluated by cumulative addition (10<jats:sup>\u22125<\/jats:sup>\u00a0<jats:sc>m<\/jats:sc> ~ 3\u00a0\u00d7\u00a010<jats:sup>\u22124<\/jats:sup>\u00a0<jats:sc>m<\/jats:sc>) to <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content> strips precontracted with 10<jats:sup>\u22125<\/jats:sup>\u00a0<jats:sc>m<\/jats:sc> phenylephrine. Western blotting analysis was performed to measure myosin phosphatase targeting subunit 1 (<jats:styled-content style=\"fixed-case\">MYPT<\/jats:styled-content>1) and protein kinase C\u2010potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17\u2010<jats:styled-content style=\"fixed-case\">kD<\/jats:styled-content>a (<jats:styled-content style=\"fixed-case\">CPI<\/jats:styled-content>\u201017) expression and to evaluate the effect of eupatilin on the RhoA\/Rho\u2010kinase pathway. Eupatilin effectively relaxed the phenylephrine\u2010induced tone in the rabbit <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content> strips in a concentration\u2010dependent manner with an estimated <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content><jats:sub>50<\/jats:sub> value of 1.2\u00a0\u00b1\u00a01.6\u00a0\u00d7\u00a010<jats:sup>\u22124<\/jats:sup>\u00a0<jats:sc>m<\/jats:sc> (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>8, <jats:italic>p\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.05). Iberiotoxin and tetraethylammonium significantly reduced the relaxation effect (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>8, <jats:italic>p\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.001 and <jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.003, respectively). Removal of the endothelium or the presence of L\u2010<jats:styled-content style=\"fixed-case\">NAME<\/jats:styled-content> or indomethacin did not affect the relaxation effect of eupatilin. In <jats:styled-content style=\"fixed-case\">CCSM<\/jats:styled-content> cells, the extracellular application of eupatilin 10<jats:sup>\u22124<\/jats:sup>\u00a0<jats:sc>m<\/jats:sc> significantly increased the outward currents, and the eupatilin\u2010stimulated currents were significantly attenuated by treatment with 10<jats:sup>\u22127<\/jats:sup>\u00a0<jats:sc>m<\/jats:sc> iberiotoxin (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>13, <jats:italic>p\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.05). Eupatilin reduced the phosphorylation level of <jats:styled-content style=\"fixed-case\">MYPT<\/jats:styled-content>1 at Thr853 of <jats:styled-content style=\"fixed-case\">MLCP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CPI<\/jats:styled-content>\u201017 at Thr38. Eupatilin\u2010induced relaxation of the <jats:styled-content style=\"fixed-case\">CCSM<\/jats:styled-content> cells via <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\u2010independent pathways. The relaxation effects of eupatilin on <jats:styled-content style=\"fixed-case\">CCSM<\/jats:styled-content> cells were partially due to activation of <jats:styled-content style=\"fixed-case\">BK<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub> channels and inhibition of RhoA\/Rho\u2010kinase.<\/jats:p>","DOI":"10.1111\/andr.12397","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T16:12:57Z","timestamp":1500394377000},"page":"1016-1022","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of eupatilin on the contractility of corpus cavernosal smooth muscle through nitric oxide\u2010independent pathways"],"prefix":"10.1111","volume":"5","author":[{"given":"S. H.","family":"Choo","sequence":"first","affiliation":[{"name":"Department of Urology Ajou University School of Medicine Suwon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6608-9050","authenticated-orcid":false,"given":"S. W.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Urology Samsung Medical Center Samsung Biomedical Research Institute Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. R.","family":"Chae","sequence":"additional","affiliation":[{"name":"Department of Urology Samsung Medical Center Samsung Biomedical Research Institute Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. J.","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Urology Samsung Medical Center Samsung Biomedical Research Institute Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. H.","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Urology Samsung Medical Center Samsung Biomedical Research Institute Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. H.","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Urology Samsung Medical Center Samsung Biomedical Research Institute Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. N.","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Sciences Seoul National University College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9682-2081","authenticated-orcid":false,"given":"J. K.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Urology Institute for Medical Sciences Medical School Chonbuk National University Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital Jeonju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Y.","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Science and Technology Hanyang University Ansan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. K.","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy Kyungsung University Busan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"So","sequence":"additional","affiliation":[{"name":"Department of Physiology Seoul National University College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,7,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.34.20246"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2003.11.002"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00717.2003"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/83258"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-008-9531-5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2008.12.004"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2011.04.011"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12143"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2011.01.018"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2011.10567.x"},{"key":"e_1_2_9_12_1","first-page":"163","article-title":"Pharmacokinetics of a new antigastritic agent, eupatilin, an active component of StillenE\u00ae, in rats","volume":"11","author":"Jang JM","year":"2003","journal-title":"Biomol Ther"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2013.17.1.31"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.856"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-006-0068-z"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5272.245"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01654-9"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2008.05.026"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsm.12183"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00111.2005"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2003.10.006"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.160606"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2014.18.5.383"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2008.03.010"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2014.278"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsm.12744"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-003-0013-1"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)03175-7"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2015.09.007"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204262200"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.093823"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2011.11.004"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2010.02.004"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2011.02218.x"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fandr.12397","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.12397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T21:59:17Z","timestamp":1695506357000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.12397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,18]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1111\/andr.12397"],"URL":"https:\/\/doi.org\/10.1111\/andr.12397","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"type":"print","value":"2047-2919"},{"type":"electronic","value":"2047-2927"}],"subject":[],"published":{"date-parts":[[2017,7,18]]},"assertion":[{"value":"2017-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}