Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro
Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid (HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppre...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2019-01-01
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| Series: | Neural Regeneration Research |
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| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2019;volume=14;issue=11;spage=1941;epage=1949;aulast=Li |
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| author | Chang-Xiang Li Xue-Qian Wang Fa-Feng Cheng Xin Yan Juan Luo Qing-Guo Wang |
| author_facet | Chang-Xiang Li Xue-Qian Wang Fa-Feng Cheng Xin Yan Juan Luo Qing-Guo Wang |
| author_sort | Chang-Xiang Li |
| collection | DOAJ |
| description | Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid (HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit (NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine (approval No. BUCM-3-2016040201-2003) in April 2016. |
| first_indexed | 2024-12-13T08:09:43Z |
| format | Article |
| id | doaj.art-145335c309b84f00892c1a29fad4a2c6 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-13T08:09:43Z |
| publishDate | 2019-01-01 |
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| series | Neural Regeneration Research |
| spelling | doaj.art-145335c309b84f00892c1a29fad4a2c62022-12-21T23:54:14ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742019-01-0114111941194910.4103/1673-5374.259617Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitroChang-Xiang LiXue-Qian WangFa-Feng ChengXin YanJuan LuoQing-Guo WangCalculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid (HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit (NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine (approval No. BUCM-3-2016040201-2003) in April 2016.http://www.nrronline.org/article.asp?issn=1673-5374;year=2019;volume=14;issue=11;spage=1941;epage=1949;aulast=Lihyodeoxycholic acid; oxygen glucose deprivation and reoxygenation; blood-brain barrier permeability; anti-oxidative; anti-inflammatory; anti-apoptotic; brain-derived neurotrophic factor; glial cell line-derived neurotrophic factor; ischemic stroke; in vitro neurovascular unit |
| spellingShingle | Chang-Xiang Li Xue-Qian Wang Fa-Feng Cheng Xin Yan Juan Luo Qing-Guo Wang Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro Neural Regeneration Research hyodeoxycholic acid; oxygen glucose deprivation and reoxygenation; blood-brain barrier permeability; anti-oxidative; anti-inflammatory; anti-apoptotic; brain-derived neurotrophic factor; glial cell line-derived neurotrophic factor; ischemic stroke; in vitro neurovascular unit |
| title | Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro |
| title_full | Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro |
| title_fullStr | Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro |
| title_full_unstemmed | Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro |
| title_short | Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro |
| title_sort | hyodeoxycholic acid protects the neurovascular unit against oxygen glucose deprivation and reoxygenation induced injury in vitro |
| topic | hyodeoxycholic acid; oxygen glucose deprivation and reoxygenation; blood-brain barrier permeability; anti-oxidative; anti-inflammatory; anti-apoptotic; brain-derived neurotrophic factor; glial cell line-derived neurotrophic factor; ischemic stroke; in vitro neurovascular unit |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2019;volume=14;issue=11;spage=1941;epage=1949;aulast=Li |
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