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Gastrodia and Uncaria (tianma gouteng) water extract exerts antioxidative and antiapoptotic effects against cerebral ischemia in vitro and in vivo

BACKGROUND: Gastrodia and Uncaria decoction (tianma gouteng yin) is commonly used in Chinese medicine to treat cerebral ischemia. The aim of this study was to investigate the neuroprotective effects of a water extract (GUW) of Gastrodia elata (tianma; GE) and Uncaria rhynchophylla (gouteng; UR) agai...

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Autores principales: Xian, Jia Wen, Choi, Angus Yiu-Ting, Lau, Clara Bik-San, Leung, Wing Nang, Ng, Chun Fai, Chan, Chun Wai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888490/
https://www.ncbi.nlm.nih.gov/pubmed/27252774
http://dx.doi.org/10.1186/s13020-016-0097-6
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author Xian, Jia Wen
Choi, Angus Yiu-Ting
Lau, Clara Bik-San
Leung, Wing Nang
Ng, Chun Fai
Chan, Chun Wai
author_facet Xian, Jia Wen
Choi, Angus Yiu-Ting
Lau, Clara Bik-San
Leung, Wing Nang
Ng, Chun Fai
Chan, Chun Wai
author_sort Xian, Jia Wen
collection PubMed
description BACKGROUND: Gastrodia and Uncaria decoction (tianma gouteng yin) is commonly used in Chinese medicine to treat cerebral ischemia. The aim of this study was to investigate the neuroprotective effects of a water extract (GUW) of Gastrodia elata (tianma; GE) and Uncaria rhynchophylla (gouteng; UR) against ischemic insult using oxygen-glucose-deprived neuronal differentiated PC12 cells and rats subjected to middle cerebral artery occlusion (MCAO). METHODS: GUW was prepared by boiling raw GE and UR in water, followed by the lyophilization of the resulting extract. Neuronal differentiated PC12 cells were subjected to oxygen-glucose deprivation with or without GUW. The neuroprotective effects of GUW were compared with those of the corresponding GE and UR extracts to tease apart the effects of the different herbs. The synergistic effect of GE and UR in GUW was measured using a modified version of Burgi’s formulae. The neuroprotective mechanisms via Nrf2 and anti-apoptotic pathways were investigated using real time PCR and enzyme activity assays. The neuroprotective effects of GUW were studied in vivo using a rat MCAO model. Neurofunctional outcome and brain infarct volume we assessed. H&E staining, cresyl violet staining and immunohistochemistry were performed to assess the histological outcome. RESULTS: The results of lactate dehydrogenase assay showed that GUW protected cells in a concentration-dependent manner (P < 0.001). Moreover, the neuroprotective effects of GUW were greater than those of GE + UR (P = 0.018). Burgi’s formula showed that the herbs in GUW acted synergistically to protect cells from ischemic injury. GUW significantly upregulated Bcl-2 expression (P = 0.0130) and reduced caspase-3 activity by 60 % (P < 0.001). GUW upregulated Nrf-2 expression (P = 0.0066) and the antioxidant response element pathway genes. The infarct volume was reduced by 55 % at day 7 of reperfusion (P < 0.001), and significant improvements were observed in the neurological deficit score and beam-walking test at 7 days (P < 0.001). H&E and cresyl violet staining revealed higher tissue integrity in the GUW treatment group compared with MCAO rats. CONCLUSION: GUW modulated the antioxidant system and antiapoptotic genes in oxygen-glucose deprived neuronal differentiated PC12 cells and MCAO sprague–dawley rats. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13020-016-0097-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-48884902016-06-02 Gastrodia and Uncaria (tianma gouteng) water extract exerts antioxidative and antiapoptotic effects against cerebral ischemia in vitro and in vivo Xian, Jia Wen Choi, Angus Yiu-Ting Lau, Clara Bik-San Leung, Wing Nang Ng, Chun Fai Chan, Chun Wai Chin Med Research BACKGROUND: Gastrodia and Uncaria decoction (tianma gouteng yin) is commonly used in Chinese medicine to treat cerebral ischemia. The aim of this study was to investigate the neuroprotective effects of a water extract (GUW) of Gastrodia elata (tianma; GE) and Uncaria rhynchophylla (gouteng; UR) against ischemic insult using oxygen-glucose-deprived neuronal differentiated PC12 cells and rats subjected to middle cerebral artery occlusion (MCAO). METHODS: GUW was prepared by boiling raw GE and UR in water, followed by the lyophilization of the resulting extract. Neuronal differentiated PC12 cells were subjected to oxygen-glucose deprivation with or without GUW. The neuroprotective effects of GUW were compared with those of the corresponding GE and UR extracts to tease apart the effects of the different herbs. The synergistic effect of GE and UR in GUW was measured using a modified version of Burgi’s formulae. The neuroprotective mechanisms via Nrf2 and anti-apoptotic pathways were investigated using real time PCR and enzyme activity assays. The neuroprotective effects of GUW were studied in vivo using a rat MCAO model. Neurofunctional outcome and brain infarct volume we assessed. H&E staining, cresyl violet staining and immunohistochemistry were performed to assess the histological outcome. RESULTS: The results of lactate dehydrogenase assay showed that GUW protected cells in a concentration-dependent manner (P < 0.001). Moreover, the neuroprotective effects of GUW were greater than those of GE + UR (P = 0.018). Burgi’s formula showed that the herbs in GUW acted synergistically to protect cells from ischemic injury. GUW significantly upregulated Bcl-2 expression (P = 0.0130) and reduced caspase-3 activity by 60 % (P < 0.001). GUW upregulated Nrf-2 expression (P = 0.0066) and the antioxidant response element pathway genes. The infarct volume was reduced by 55 % at day 7 of reperfusion (P < 0.001), and significant improvements were observed in the neurological deficit score and beam-walking test at 7 days (P < 0.001). H&E and cresyl violet staining revealed higher tissue integrity in the GUW treatment group compared with MCAO rats. CONCLUSION: GUW modulated the antioxidant system and antiapoptotic genes in oxygen-glucose deprived neuronal differentiated PC12 cells and MCAO sprague–dawley rats. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13020-016-0097-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-31 /pmc/articles/PMC4888490/ /pubmed/27252774 http://dx.doi.org/10.1186/s13020-016-0097-6 Text en © Xian et al 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Xian, Jia Wen
Choi, Angus Yiu-Ting
Lau, Clara Bik-San
Leung, Wing Nang
Ng, Chun Fai
Chan, Chun Wai
Gastrodia and Uncaria (tianma gouteng) water extract exerts antioxidative and antiapoptotic effects against cerebral ischemia in vitro and in vivo
title Gastrodia and Uncaria (tianma gouteng) water extract exerts antioxidative and antiapoptotic effects against cerebral ischemia in vitro and in vivo
title_full Gastrodia and Uncaria (tianma gouteng) water extract exerts antioxidative and antiapoptotic effects against cerebral ischemia in vitro and in vivo
title_fullStr Gastrodia and Uncaria (tianma gouteng) water extract exerts antioxidative and antiapoptotic effects against cerebral ischemia in vitro and in vivo
title_full_unstemmed Gastrodia and Uncaria (tianma gouteng) water extract exerts antioxidative and antiapoptotic effects against cerebral ischemia in vitro and in vivo
title_short Gastrodia and Uncaria (tianma gouteng) water extract exerts antioxidative and antiapoptotic effects against cerebral ischemia in vitro and in vivo
title_sort gastrodia and uncaria (tianma gouteng) water extract exerts antioxidative and antiapoptotic effects against cerebral ischemia in vitro and in vivo
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888490/
https://www.ncbi.nlm.nih.gov/pubmed/27252774
http://dx.doi.org/10.1186/s13020-016-0097-6
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