{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T09:27:43Z","timestamp":1782552463050,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,5,15]],"date-time":"2021-05-15T00:00:00Z","timestamp":1621036800000},"content-version":"vor","delay-in-days":134,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010226","name":"Department of Education of Guangdong Province","doi-asserted-by":"publisher","award":["2016KCXTD015"],"award-info":[{"award-number":["2016KCXTD015"]}],"id":[{"id":"10.13039\/501100010226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010618","name":"Guangzhou University of Chinese Medicine","doi-asserted-by":"publisher","award":["2017GC010361"],"award-info":[{"award-number":["2017GC010361"]}],"id":[{"id":"10.13039\/501100010618","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Gentiopicroside (GPS), a main active secoiridoid glucoside derived from the roots of perennial herbs in the <jats:italic>Gentianaceae<\/jats:italic> family, has antispasmodic and relaxant effects. However, the vasorelaxant effects of GPS on aortic rings and the molecular mechanisms involved in these effects are not yet clear. Therefore, we investigated whether GPS inhibits phenylephrine\u2010 (PE\u2010) or KCl\u2010induced contractions in isolated rat thoracic aortic rings. The present study found that GPS produced a dose\u2010dependent relaxation in aortic rings precontracted with PE or KCl and significantly reduced CaCl<jats:sub>2<\/jats:sub>\u2010, narciclasine\u2010 (Rho\u2010kinase activator\u2010), and phorbol\u201012,13\u2010diacetate\u2010 (PKC activator\u2010) induced vasocontractions. Pretreatment with NG\u2010Nitroarginine methyl ester hydrochloride (L\u2010NAME, NOS inhibitor), methylene blue (sGC inhibitor), indomethacin (COX inhibitor), 4\u2010aminopyridine (K<jats:sub>V<\/jats:sub> channel inhibitor), and glibenclamide (K<jats:sub>ATP<\/jats:sub> channel inhibitor) had no influence on the vasorelaxant effect of GPS, while BaCl<jats:sub>2<\/jats:sub> (K<jats:sub>ir<\/jats:sub> channel inhibitor), tetraethylammonium chloride (K<jats:sub>Ca<\/jats:sub> channel inhibitor), ruthenium red (RYR inhibitor), and heparin (IP<jats:sub>3<\/jats:sub>R inhibitor) significantly reduced GPS\u2010induced vasorelaxation. Moreover, GPS pretreatment remarkably inhibited the influx of Ca<jats:sup>2+<\/jats:sup> in vascular smooth muscle cells stimulated using KCl or PE\u2010containing CaCl<jats:sub>2<\/jats:sub> solution. Western blot analysis confirmed that GPS treatment inhibited PE\u2010induced increases in the protein levels of p\u2010Akt, p\u2010myosin light chain (MLC), and p\u2010myosin\u2010binding subunit of myosin phosphatase 1 (MYPT1) in the aortic rings. Additionally, the vasorelaxation activity of GPS was attenuated upon pretreatment with LY294002 (PI3K\/Akt inhibitor), Y27632 (Rho\u2010kinase inhibitor), and verapamil (L\u2010type Ca<jats:sup>2+<\/jats:sup> channel inhibitor). These findings demonstrate that GPS exhibits endothelium\u2010independent vasorelaxant effects through inhibition of voltage\u2010dependent, receptor\u2010operated, and inositol triphosphate receptor (IP<jats:sub>3<\/jats:sub>R)\/ryanodine receptor\u2010 (RYR\u2010) mediated Ca<jats:sup>2+<\/jats:sup> channels as well as the PI3K\/Akt\/Rho\u2010kinase signaling pathway.<\/jats:p>","DOI":"10.1155\/2021\/5565748","type":"journal-article","created":{"date-parts":[[2021,5,15]],"date-time":"2021-05-15T18:20:05Z","timestamp":1621102805000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Gentiopicroside Produces Endothelium\u2010Independent Vasodilation by Deactivating the PI3K\/Akt\/Rho\u2010Kinase Pathway in Isolated Rat Thoracic Aorta"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7252-7176","authenticated-orcid":false,"given":"Shangping","family":"Xing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2306-0108","authenticated-orcid":false,"given":"Feifei","family":"Nong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6513-9447","authenticated-orcid":false,"given":"Jialiang","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8813-1499","authenticated-orcid":false,"given":"Huicai","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2469-4812","authenticated-orcid":false,"given":"Ruoting","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2628-4254","authenticated-orcid":false,"given":"Weiwen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,15]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.04.038"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2018.08.007"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(83)80084-9"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00053038"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/2690296"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17741-1"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(84)80032-7"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000726"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0195780"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00852"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.02.012"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.4103\/pr.pr_140_16"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00055"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.04.005"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn325"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.241315"},{"key":"e_1_2_10_17_2","first-page":"885","article-title":"Pulmonary vasodilators","volume":"52","author":"Siobal M. 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