{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:05:37Z","timestamp":1793811937338,"version":"4.6.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T00:00:00Z","timestamp":1559088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007156","name":"Innovation and Technology Commission - Hong Kong","doi-asserted-by":"publisher","award":["UIM\/289, InP\/246\/17"],"award-info":[{"award-number":["UIM\/289, InP\/246\/17"]}],"id":[{"id":"10.13039\/501100007156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2019.00593","type":"journal-article","created":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T05:44:49Z","timestamp":1559108689000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":54,"title":["Neuroprotective Effects and Hepatorenal Toxicity of Angong Niuhuang Wan Against Ischemia\u2013Reperfusion Brain Injury in Rats"],"prefix":"10.3389","volume":"10","author":[{"given":"Bun","family":"Tsoi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingmiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songlin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sau Chu","family":"Yuen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Depo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1111\/j.1471-4159.2012.07952.x","article-title":"Plasma 3-nitrotyrosine estimates the reperfusion-induced cerebrovascular stress, whereas matrix metalloproteinases mainly reflect plasma activity: a study in patients treated with thrombolysis or endovascular recanalization","volume":"123","author":"Bas","year":"2012","journal-title":"J. Neurochem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1161\/STROKEAHA.106.481556","article-title":"Serum cellular fibronectin and matrix metalloproteinase-9 as screening biomarkers for the prediction of parenchymal hematoma after thrombolytic therapy in acute ischemic stroke: a multicenter confirmatory study","volume":"38","author":"Castellanos","year":"2007","journal-title":"Stroke"},{"key":"B3","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1161\/CIRCRESAHA.116.309278","article-title":"Acute ischemic stroke therapy overview","volume":"120","author":"Catanese","year":"2017","journal-title":"Circ. Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1080\/10715762.2018.1521519","article-title":"Potential molecular targets of peroxynitrite in mediating blood\u2013brain barrier damage and haemorrhagic transformation in acute ischaemic stroke with delayed tissue plasminogen activator treatment","volume":"52","author":"Chen","year":"2018","journal-title":"Free Radic. Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1007\/s12975-017-0598-3","article-title":"Baicalin attenuates blood\u2013brain barrier disruption and hemorrhagic transformation and improves neurological outcome in ischemic stroke rats with delayed t-PA treatment: involvement of ONOO\u2013MMP-9 Pathway","volume":"9","author":"Chen","year":"2018","journal-title":"Transl. Stroke Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1111\/cns.12406","article-title":"Peroxynitrite decomposition catalyst reduces delayed thrombolysis-induced hemorrhagic transformation in ischemia-reperfused rat brains","volume":"21","author":"Chen","year":"2015","journal-title":"CNS Neurosci. Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/aps.2012.82","article-title":"Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia\u2013reperfusion injury","volume":"34","author":"Chen","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"B8","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/S0165-6147(00)01972-6","article-title":"Toxic heavy metals and undeclared drugs in Asian herbal medicines","volume":"23","author":"Ernst","year":"2002","journal-title":"Trends Pharmacol. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/S1474-4422(17)30299-5","article-title":"Global, regional, and national burden of neurological disorders during 1990\u20132015: a systematic analysis for the Global Burden of Disease Study 2015","volume":"16","author":"Feigin","year":"2017","journal-title":"Lancet Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"6369","DOI":"10.1007\/s12035-017-0859-x","article-title":"Inhibition of peroxynitrite-induced mitophagy activation attenuates cerebral ischemia\u2013reperfusion injury","volume":"55","author":"Feng","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"9029","DOI":"10.1007\/s12035-018-1027-7","article-title":"Naringin attenuates cerebral ischemia\u2013reperfusion injury through inhibiting peroxynitrite-mediated mitophagy activation","volume":"55","author":"Feng","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1097\/00004647-200112000-00003","article-title":"Matrix metalloproteinase inhibition prevents oxidative stress-associated blood\u2013brain barrier disruption after transient focal cerebral ischemia","volume":"21","author":"Gasche","year":"2001","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B13","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1111\/j.1471-4159.2011.07542.x","article-title":"Caveolin-1 regulates nitric oxide-mediated matrix metalloproteinases activity and blood\u2013brain barrier permeability in focal cerebral ischemia and reperfusion injury","volume":"120","author":"Gu","year":"2012","journal-title":"J. Neurochem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/346918","article-title":"Use of Angong Niuhuang in treating central nervous system diseases and related research","volume":"2014","author":"Guo","year":"2014","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.freeradbiomed.2005.03.033","article-title":"Matrix metalloproteinases and free radicals in cerebral ischemia","volume":"39","author":"Jian Liu","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00032","article-title":"Matrix metalloproteinases and blood\u2013brain barrier disruption in acute ischemic stroke","volume":"4","author":"Lakhan","year":"2013","journal-title":"Front Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.yrtph.2011.03.007","article-title":"Evaluation of hepatotoxicity potential of cinnabar-containing An-Gong-Niu-Huang Wan, a patent traditional Chinese medicine","volume":"60","author":"Lu","year":"2011","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1258\/ebm.2010.010247","article-title":"Realgar, cinnabar and An-Gong-Niu-Huang Wan are much less chronically nephrotoxic than common arsenicals and mercurials","volume":"236","author":"Lu","year":"2011","journal-title":"Exp. Biol. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.cbi.2010.11.006","article-title":"Realgar-and cinnabar-containing An-Gong-Niu-Huang Wan (AGNH) is much less acutely toxic than sodium arsenite and mercuric chloride","volume":"189","author":"Lu","year":"2011","journal-title":"Chem. Biol. Interact."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00491","article-title":"Accumulation of arsenic speciation and in vivo toxicity following oral administration of a Chinese patent medicine Xiao-Er-Zhi-Bao-Wan in rats","volume":"8","author":"Luo","year":"2017","journal-title":"Front Pharmacol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"45","DOI":"10.3969\/j.issn.1007-8517.2009.10.029","article-title":"Angongniuhuang Pill treatment of acute stroke clinical observation of 64 cases","volume":"10","author":"Luo","year":"2009","journal-title":"Chin. J. Ethnomed. Ethnopharm."},{"key":"B22","doi-asserted-by":"publisher","first-page":"64","DOI":"10.3969\/j.issn.0256-7415.2001.12.047","article-title":"The survey on the application of Angong Niuhuang Wan and analogous prescription","volume":"33","author":"Pan","year":"2001","journal-title":"J. New Chin. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1136\/neurintsurg-2016-012515","article-title":"A population-based incidence of acute large vessel occlusions and thrombectomy eligible patients indicates significant potential for growth of endovascular stroke therapy in the USA","volume":"9","author":"Rai","year":"2016","journal-title":"J Neurointerv. Surg."},{"key":"B24","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.nbd.2008.08.005","article-title":"Blood\u2013brain barrier tight junction permeability and ischemic stroke","volume":"32","author":"Sandoval","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1161\/01.STR.0000196957.55928.ab","article-title":"Time is brain-quantified","volume":"37","author":"Saver","year":"2006","journal-title":"Stroke"},{"key":"B26","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/S0006-8993(02)03145-1","article-title":"Concurrent formation of peroxynitrite with the expression of inducible nitric oxide synthase in the brain during middle cerebral artery occlusion and reperfusion in rats","volume":"951","author":"Suzuki","year":"2002","journal-title":"Brain Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/sj.bjp.0705811","article-title":"Neuroprotective efficacy and therapeutic time window of peroxynitrite decomposition catalysts in focal cerebral ischemia in rats","volume":"142","author":"Thiyagarajan","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.yrtph.2016.01.010","article-title":"Bioavailability study of arsenic and mercury in traditional Chinese medicines (TCM) using an animal model after a single dose exposure","volume":"76","author":"Tinggi","year":"2016","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.jep.2014.03.057","article-title":"An-Gong-Niu-Huang Wan protects against cerebral ischemia induced apoptosis in rats: up-regulation of Bcl-2 and down-regulation of Bax and caspase-3","volume":"154","author":"Wang","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/278931","article-title":"Cinnabar-induced subchronic renal injury is associated with increased apoptosis in rats","volume":"2015","author":"Wang","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"B31","doi-asserted-by":"publisher","first-page":"397","DOI":"10.3969\/j.issn.1004-2814.2010.06.025","article-title":"Observation on 60 cases of acute cerebral infarction treated by combination of traditional Chinese medicine and Western medicine","volume":"6","author":"Wang","year":"2010","journal-title":"J. Pract. Tradit. Chin. Med."},{"key":"B32","unstructured":"\u201cGlobal Health Estimates 2016: Disease burden by Cause, Age, Sex, by Country and by Region, 2000-2016.\u201d The top 10 causes of death2018"},{"key":"B33","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.jep.2011.01.031","article-title":"Chemical form of metals in traditional medicines underlines potential toxicity in cell cultures","volume":"134","author":"Wu","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"550","DOI":"10.13748\/j.cnki.issn1007-7693.2012.06.001","article-title":"Effects of Angong Niuhuang pills on plasma BNP and CRP and neurological functional defect in patients with acute cerebral infarction","volume":"29","author":"Wu","year":"2012","journal-title":"Chin. J. Mod. Appl. Pharm."},{"key":"B35","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3969\/j.issn.1002-2619.2005.01.005","article-title":"Therapeutic effects of Angongniuhuang pill on 34 patients with cerebral stroke","volume":"27","author":"Xing","year":"2005","journal-title":"Hebei J. Tradit. Chin. Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"151","DOI":"10.3969\/j.issn.1673-7555.2013.01.119","article-title":"90 Cases of cerebral hemorrhage disease using traditional Chinese medicine and Western medicine treatment","author":"Zhang","year":"2013","journal-title":"Chin. Pract. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S0165-0270(02)00114-0","article-title":"A test for detecting long-term sensorimotor dysfunction in the mouse after focal cerebral ischemia","volume":"117","author":"Zhang","year":"2002","journal-title":"J. Neurosci. Methods"},{"key":"B38","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.brainres.2012.03.065","article-title":"Neuroprotection of early and short-time applying berberine in the acute phase of cerebral ischemia: up-regulated pAkt, pGSK and pCREB, down-regulated NF-\u03baB expression, ameliorated BBB permeability","volume":"1459","author":"Zhang","year":"2012","journal-title":"Brain Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.jep.2011.02.032","article-title":"Cinnabar is not converted into methylmercury by human intestinal bacteria","volume":"135","author":"Zhou","year":"2011","journal-title":"J. Ethnopharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.00593\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T05:44:56Z","timestamp":1559108696000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.00593\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,29]]},"references-count":39,"alternative-id":["10.3389\/fphar.2019.00593"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2019.00593","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,29]]},"article-number":"593"}}