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Article: Neuroprotective Effects and Hepatorenal Toxicity of Angong Niuhuang Wan Against Ischemia–Reperfusion Brain Injury in Rats

TitleNeuroprotective Effects and Hepatorenal Toxicity of Angong Niuhuang Wan Against Ischemia–Reperfusion Brain Injury in Rats
Authors
KeywordsAngong Niuhuang Wan
Blood–brain barrier
Cerebral ischemia–reperfusion injury
Heavy metal
Safety
Issue Date2019
PublisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/pharmacology
Citation
Frontiers in Pharmacology, 2019, v. 10, article no. 593 How to Cite?
AbstractAngong Niuhuang Wan (AGNHW) is a classic prescription in traditional Chinese medicine (TCM) used for stroke treatment, but its efficacies remain to be confirmed. With its arsenic- and mercury-containing materials, the application of AGNHW raises great safety concerns. Herein, we aim to explore the neuropharmacological effects against cerebral ischemia–reperfusion injury and evaluate the toxicological effects of AGNHW for better use. Male SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) and following 22 h of reperfusion. AGNHW (257 mg/kg, 1× AGNHW) were orally administered for pharmacological effects and 257, 514, and 1,028 mg/kg (equivalent to 1×, 2×, 4× AGNHW) were used for the toxicological study. The results revealed that AGNHW treatment reduced the infarct size and protected the blood–brain barrier (BBB) integrity in the MCAO rat ischemic stroke model. AGNHW treatment up-regulated bcl-2 expression and down-regulated the expressions of Bax, p47phox, inducible nitric oxide synthase (iNOS), and 3-nitrotyrosine (3-NT), and inhibited the expressions and activities of matrix metalloproteinase-2 (MMP-2), MMP-9, and reserved tight junction protein zonula occludens-1 (ZO-1) and claudin-5 in the ischemic brains. These results indicated that the neuroprotective mechanisms of AGNHW could be associated with its antioxidant properties by inhibiting oxidative/nitrative stress-mediated MMP activation and protecting tight junction proteins in the ischemic brains. Administration of 1× AGNHW for 7 days would not induce the accumulation of mercury in blood, liver, and kidney at day 14. Administration of 2× AGNHW and 4× AGNHW for 7 days increased the level of mercury in the kidney. For arsenic level, administration of 1× AGNHW for 7 days would increase the level of arsenic in the liver and blood without increase of arsenic in the kidney at day 14. Administration of 2× AGNHW and 4× AGNHW for 7 days would further increase the level of arsenic in the liver and blood. There is no influence on body weight, organ index, histological structures, and renal and liver functions. These results suggest that short-term treatment of AGNHW within 1 week should be safe and has neuroprotective effects against cerebral ischemia–reperfusion injury.
Persistent Identifierhttp://hdl.handle.net/10722/274313
ISSN
2017 Impact Factor: 3.831
2015 SCImago Journal Rankings: 1.845
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTsoi, B-
dc.contributor.authorChen, X-
dc.contributor.authorGao, C-
dc.contributor.authorWang, S-
dc.contributor.authorYuen, SC-
dc.contributor.authorYang, D-
dc.contributor.authorShen, J-
dc.date.accessioned2019-08-18T14:59:15Z-
dc.date.available2019-08-18T14:59:15Z-
dc.date.issued2019-
dc.identifier.citationFrontiers in Pharmacology, 2019, v. 10, article no. 593-
dc.identifier.issn1663-9812-
dc.identifier.urihttp://hdl.handle.net/10722/274313-
dc.description.abstractAngong Niuhuang Wan (AGNHW) is a classic prescription in traditional Chinese medicine (TCM) used for stroke treatment, but its efficacies remain to be confirmed. With its arsenic- and mercury-containing materials, the application of AGNHW raises great safety concerns. Herein, we aim to explore the neuropharmacological effects against cerebral ischemia–reperfusion injury and evaluate the toxicological effects of AGNHW for better use. Male SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) and following 22 h of reperfusion. AGNHW (257 mg/kg, 1× AGNHW) were orally administered for pharmacological effects and 257, 514, and 1,028 mg/kg (equivalent to 1×, 2×, 4× AGNHW) were used for the toxicological study. The results revealed that AGNHW treatment reduced the infarct size and protected the blood–brain barrier (BBB) integrity in the MCAO rat ischemic stroke model. AGNHW treatment up-regulated bcl-2 expression and down-regulated the expressions of Bax, p47phox, inducible nitric oxide synthase (iNOS), and 3-nitrotyrosine (3-NT), and inhibited the expressions and activities of matrix metalloproteinase-2 (MMP-2), MMP-9, and reserved tight junction protein zonula occludens-1 (ZO-1) and claudin-5 in the ischemic brains. These results indicated that the neuroprotective mechanisms of AGNHW could be associated with its antioxidant properties by inhibiting oxidative/nitrative stress-mediated MMP activation and protecting tight junction proteins in the ischemic brains. Administration of 1× AGNHW for 7 days would not induce the accumulation of mercury in blood, liver, and kidney at day 14. Administration of 2× AGNHW and 4× AGNHW for 7 days increased the level of mercury in the kidney. For arsenic level, administration of 1× AGNHW for 7 days would increase the level of arsenic in the liver and blood without increase of arsenic in the kidney at day 14. Administration of 2× AGNHW and 4× AGNHW for 7 days would further increase the level of arsenic in the liver and blood. There is no influence on body weight, organ index, histological structures, and renal and liver functions. These results suggest that short-term treatment of AGNHW within 1 week should be safe and has neuroprotective effects against cerebral ischemia–reperfusion injury.-
dc.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/pharmacology-
dc.relation.ispartofFrontiers in Pharmacology-
dc.rightsThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAngong Niuhuang Wan-
dc.subjectBlood–brain barrier-
dc.subjectCerebral ischemia–reperfusion injury-
dc.subjectHeavy metal-
dc.subjectSafety-
dc.titleNeuroprotective Effects and Hepatorenal Toxicity of Angong Niuhuang Wan Against Ischemia–Reperfusion Brain Injury in Rats-
dc.typeArticle-
dc.identifier.emailTsoi, B: amytsoi@hku.hk-
dc.identifier.emailGao, C: colingao@hku.hk-
dc.identifier.emailShen, J: shenjg@hku.hk-
dc.identifier.authorityShen, J=rp00487-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fphar.2019.00593-
dc.identifier.scopuseid_2-s2.0-85067923788-
dc.identifier.hkuros301282-
dc.identifier.volume10-
dc.identifier.spagearticle no. 593-
dc.identifier.epagearticle no. 593-
dc.identifier.isiWOS:000469473900001-
dc.publisher.placeSwitzerland-

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