Cargando…

Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats

Puerarin, a major isoflavonoid derived from the Chinese medical herb Radix puerariae (kudzu root), has been reported to be useful in the treatment of various cardiovascular diseases. In the present study, we examined the detailed mechanisms underlying the inhibitory effects of puerarin on inflammato...

Descripción completa

Detalles Bibliográficos
Autores principales: Chang, Yi, Hsieh, Cheng-Ying, Peng, Zi-Aa, Yen, Ting-Lin, Hsiao, George, Chou, Duen-Suey, Chen, Chien-Ming, Sheu, Joen-Rong
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653511/
https://www.ncbi.nlm.nih.gov/pubmed/19272172
http://dx.doi.org/10.1186/1423-0127-16-9
_version_ 1782165283746611200
author Chang, Yi
Hsieh, Cheng-Ying
Peng, Zi-Aa
Yen, Ting-Lin
Hsiao, George
Chou, Duen-Suey
Chen, Chien-Ming
Sheu, Joen-Rong
author_facet Chang, Yi
Hsieh, Cheng-Ying
Peng, Zi-Aa
Yen, Ting-Lin
Hsiao, George
Chou, Duen-Suey
Chen, Chien-Ming
Sheu, Joen-Rong
author_sort Chang, Yi
collection PubMed
description Puerarin, a major isoflavonoid derived from the Chinese medical herb Radix puerariae (kudzu root), has been reported to be useful in the treatment of various cardiovascular diseases. In the present study, we examined the detailed mechanisms underlying the inhibitory effects of puerarin on inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAO) in rats. Treatment of puerarin (25 and 50 mg/kg; intraperitoneally) 10 min before MCAO dose-dependently attenuated focal cerebral ischemia in rats. Administration of puerarin at 50 mg/kg, showed marked reduction in infarct size compared with that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), and active caspase-3 protein expressions as well as the mRNA expression of tumor necrosis factor-α (TNF-α) in ischemic regions. These expressions were markedly inhibited by the treatment of puerarin (50 mg/kg). In addition, puerarin (10~50 μM) concentration-dependently inhibited respiratory bursts in human neutrophils stimulated by formyl-Met-Leu-Phe. On the other hand, puerarin (20~500 μM) did not significantly inhibit the thiobarbituric acid-reactive substance reaction in rat brain homogenates. An electron spin resonance (ESR) method was conducted on the scavenging activity of puerarin on the free radicals formed. Puerarin (200 and 500 μM) did not reduce the ESR signal intensity of hydroxyl radical formation. In conclusion, we demonstrate that puerarin is a potent neuroprotective agent on MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1α and TNF-α activation, followed by the inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation (active caspase-3), and neutrophil activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, puerarin treatment may represent a novel approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders.
format Text
id pubmed-2653511
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-26535112009-03-10 Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats Chang, Yi Hsieh, Cheng-Ying Peng, Zi-Aa Yen, Ting-Lin Hsiao, George Chou, Duen-Suey Chen, Chien-Ming Sheu, Joen-Rong J Biomed Sci Research Puerarin, a major isoflavonoid derived from the Chinese medical herb Radix puerariae (kudzu root), has been reported to be useful in the treatment of various cardiovascular diseases. In the present study, we examined the detailed mechanisms underlying the inhibitory effects of puerarin on inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAO) in rats. Treatment of puerarin (25 and 50 mg/kg; intraperitoneally) 10 min before MCAO dose-dependently attenuated focal cerebral ischemia in rats. Administration of puerarin at 50 mg/kg, showed marked reduction in infarct size compared with that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), and active caspase-3 protein expressions as well as the mRNA expression of tumor necrosis factor-α (TNF-α) in ischemic regions. These expressions were markedly inhibited by the treatment of puerarin (50 mg/kg). In addition, puerarin (10~50 μM) concentration-dependently inhibited respiratory bursts in human neutrophils stimulated by formyl-Met-Leu-Phe. On the other hand, puerarin (20~500 μM) did not significantly inhibit the thiobarbituric acid-reactive substance reaction in rat brain homogenates. An electron spin resonance (ESR) method was conducted on the scavenging activity of puerarin on the free radicals formed. Puerarin (200 and 500 μM) did not reduce the ESR signal intensity of hydroxyl radical formation. In conclusion, we demonstrate that puerarin is a potent neuroprotective agent on MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1α and TNF-α activation, followed by the inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation (active caspase-3), and neutrophil activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, puerarin treatment may represent a novel approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders. BioMed Central 2009-01-19 /pmc/articles/PMC2653511/ /pubmed/19272172 http://dx.doi.org/10.1186/1423-0127-16-9 Text en Copyright © 2009 Chang et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Chang, Yi
Hsieh, Cheng-Ying
Peng, Zi-Aa
Yen, Ting-Lin
Hsiao, George
Chou, Duen-Suey
Chen, Chien-Ming
Sheu, Joen-Rong
Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats
title Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats
title_full Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats
title_fullStr Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats
title_full_unstemmed Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats
title_short Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats
title_sort neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653511/
https://www.ncbi.nlm.nih.gov/pubmed/19272172
http://dx.doi.org/10.1186/1423-0127-16-9
work_keys_str_mv AT changyi neuroprotectivemechanismsofpuerarininmiddlecerebralarteryocclusioninducedbraininfarctioninrats
AT hsiehchengying neuroprotectivemechanismsofpuerarininmiddlecerebralarteryocclusioninducedbraininfarctioninrats
AT pengziaa neuroprotectivemechanismsofpuerarininmiddlecerebralarteryocclusioninducedbraininfarctioninrats
AT yentinglin neuroprotectivemechanismsofpuerarininmiddlecerebralarteryocclusioninducedbraininfarctioninrats
AT hsiaogeorge neuroprotectivemechanismsofpuerarininmiddlecerebralarteryocclusioninducedbraininfarctioninrats
AT chouduensuey neuroprotectivemechanismsofpuerarininmiddlecerebralarteryocclusioninducedbraininfarctioninrats
AT chenchienming neuroprotectivemechanismsofpuerarininmiddlecerebralarteryocclusioninducedbraininfarctioninrats
AT sheujoenrong neuroprotectivemechanismsofpuerarininmiddlecerebralarteryocclusioninducedbraininfarctioninrats