{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:30:17Z","timestamp":1777667417112,"version":"3.51.4"},"reference-count":41,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:00:00Z","timestamp":1619395200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"the Project of Guangxi Key Laboratory of Chinese Medicine Foundation Research","award":["19-245-14-05"],"award-info":[{"award-number":["19-245-14-05"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:p>Some traditional Chinese decoctions, such as Zhuyu Annao, exert favorable therapeutic effects on acute cerebral hemorrhage, hemorrhagic stroke, and other neurological diseases, but the underlying mechanism remains unclear. This study aimed to determine whether Zhuyu Annao decoction (ZYAND) protects the injured brain by promoting angiogenesis following intracerebral hemorrhage (ICH) and elucidate its specific mechanism. The effect of ZYAND on the nervous system of mice after ICH was explored through behavioral experiments, such as the Morris water maze and Rotarod tests, and its effects on oxidative stress were explored by detecting several oxidative stress markers, including malondialdehyde, nitric oxide, glutathione peroxidase, and superoxide dismutase. Real-time quantitative RT-PCR and WB were used to detect the effects of ZYAND on the levels of prolyl hydroxylase domain 3 (PHD3), hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), and vascular endothelial growth factor (VEGF) in the brain tissues of mice. The effect of ZYAND on the NF-\u03baB signaling pathway was detected using a luciferase reporter gene. A human umbilical cord vascular endothelial cell angiogenesis experiment was performed to determine whether ZYAND promotes angiogenesis. The Morris water maze test and other behavioral experiments verified that ZYAND improved the neurobehavior of mice after ICH. ZYAND activated the PHD3\/HIF-1\u03b1 signaling pathway, inhibiting the oxidative damage caused by ICH. In angiogenesis experiments, it was found that ZYAND promoted VEGF-induced angiogenesis by upregulating the expression of HIF-1\u03b1, and NF-\u03baB signaling regulated the expression of HIF-1\u03b1 by inhibiting PHD3. ZYAND exerts a reparative effect on brain tissue damaged after ICH through the NF-\u03baB\/ PHD3\/HIF-1\u03b1\/VEGF signaling axis.<\/jats:p>","DOI":"10.1177\/09603271211008523","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T03:51:50Z","timestamp":1619409110000},"page":"1867-1879","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Zhuyu Annao decoction promotes angiogenesis in mice with cerebral hemorrhage by inhibiting the activity of PHD3"],"prefix":"10.1177","volume":"40","author":[{"given":"L","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, China"},{"name":"Guangxi Key Laboratory of Chinese Medicine Foundation Research, Guangxi University of Chinese Medicine, China"},{"name":"Scientific Laboratorial Centre Guangxi University of Chinese Medicine, China"},{"name":"Both authors contributed equally to this work and should be considered as equal first coauthors."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, China"},{"name":"Guangxi Key Laboratory of Chinese Medicine Foundation Research, Guangxi University of Chinese Medicine, China"},{"name":"Both authors contributed equally to this work and should be considered as equal first coauthors."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Jiang","sequence":"additional","affiliation":[{"name":"Graduate College of Guangxi University of Traditional Chinese Medicine, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Disease, Traditional Medicine Hospital Affiliated to Southwest Medical University, Luzhou, Sichuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Hong","sequence":"additional","affiliation":[{"name":"Graduate College of Guangxi University of Traditional Chinese Medicine, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Yang","sequence":"additional","affiliation":[{"name":"National Traditional Chinese Medicine Clinical Research Base, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9178-444X","authenticated-orcid":false,"given":"W","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, China"},{"name":"Guangxi Key Laboratory of Chinese Medicine Foundation Research, Guangxi University of Chinese Medicine, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,4,26]]},"reference":[{"key":"bibr1-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.020688"},{"key":"bibr2-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.07.724"},{"key":"bibr3-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.116.013186"},{"key":"bibr4-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14336"},{"key":"bibr5-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00851-z"},{"key":"bibr6-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.009357"},{"key":"bibr7-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.264"},{"key":"bibr8-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2592935"},{"key":"bibr9-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.01.015"},{"key":"bibr10-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2018.03.003"},{"key":"bibr11-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2012.08.014"},{"key":"bibr12-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1509-8"},{"key":"bibr13-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-018-0636-9"},{"key":"bibr14-09603271211008523","first-page":"241","volume":"28","author":"Li HT","year":"2018","journal-title":"Turk Neurosurg"},{"key":"bibr15-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2018.10.006"},{"key":"bibr16-09603271211008523","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X16666180110130253"},{"key":"bibr17-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.669598"},{"key":"bibr18-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1039\/C8CP01964A"},{"key":"bibr19-09603271211008523","first-page":"39","volume":"037","author":"Wu Z","year":"2005","journal-title":"J New Chin Med"},{"key":"bibr20-09603271211008523","first-page":"383","year":"2010","journal-title":"Shi-Zhen"},{"key":"bibr21-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.14.9828"},{"key":"bibr22-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1198-2"},{"key":"bibr23-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-015-0272-9"},{"key":"bibr24-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.01.026"},{"key":"bibr25-09603271211008523","doi-asserted-by":"publisher","DOI":"10.2741\/2892"},{"key":"bibr26-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.12.007"},{"key":"bibr27-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084767"},{"key":"bibr28-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2711"},{"key":"bibr29-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18762645"},{"key":"bibr30-09603271211008523","first-page":"191","volume":"9","author":"Mu SW","year":"2018","journal-title":"Biomed Rep"},{"key":"bibr31-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.05.012"},{"key":"bibr32-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-0917-z"},{"key":"bibr33-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-016-0862-0"},{"key":"bibr34-09603271211008523","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S228773"},{"key":"bibr35-09603271211008523","first-page":"7301","volume":"17","author":"Zhao Q","year":"2018","journal-title":"Mol Med Rep"},{"key":"bibr36-09603271211008523","first-page":"4065","volume":"18","author":"Fei Z","year":"2018","journal-title":"Mol Med Rep"},{"key":"bibr37-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19419-6"},{"key":"bibr38-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.020138"},{"key":"bibr39-09603271211008523","doi-asserted-by":"publisher","DOI":"10.5582\/bst.2018.01061"},{"key":"bibr40-09603271211008523","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2016.00864"},{"key":"bibr41-09603271211008523","doi-asserted-by":"publisher","DOI":"10.1016\/j.apjtm.2016.09.004"}],"container-title":["Human &amp; Experimental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09603271211008523","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/09603271211008523","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09603271211008523","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:46:41Z","timestamp":1777448801000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/09603271211008523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,26]]},"references-count":41,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1177\/09603271211008523"],"URL":"https:\/\/doi.org\/10.1177\/09603271211008523","relation":{},"ISSN":["0960-3271","1477-0903"],"issn-type":[{"value":"0960-3271","type":"print"},{"value":"1477-0903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,26]]}}}