Protective effects of berbamine against arginase-1 deficiency-induced injury in human brain microvascular endothelial cells
Endothelial cell dysfunction plays a crucial role in the early development of cerebral small vessel disease (CSVD). Arginase-1 (ARG1) is expressed in endothelial cells, and its deficiency may exacerbate cerebrovascular damage by increasing reactive oxygen species (ROS) production, thereby inducing e...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1497973/full |
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| author | Xiaolan Wei Weiwei Li Zixuan Chen Jintu Chen Yun Chen Jiangping Cai Huasong Lin |
| author_facet | Xiaolan Wei Weiwei Li Zixuan Chen Jintu Chen Yun Chen Jiangping Cai Huasong Lin |
| author_sort | Xiaolan Wei |
| collection | DOAJ |
| description | Endothelial cell dysfunction plays a crucial role in the early development of cerebral small vessel disease (CSVD). Arginase-1 (ARG1) is expressed in endothelial cells, and its deficiency may exacerbate cerebrovascular damage by increasing reactive oxygen species (ROS) production, thereby inducing endothelial cell apoptosis. Berbamine (BBM) has shown potential in neuroprotection and cardiovascular disease prevention. This study aimed to investigate the impact of ARG1 deficiency on human brain microvascular endothelial cells and the protective effects of BBM against ARG1 deficiency-induced damage. Human brain microvascular endothelial cells (HCMEC/D3) were cultured in vitro, and ARG1 knockdown or overexpression was achieved using plasmid transfection techniques. We examined the effects of ARG1 expression levels on HCMEC/D3 cell viability, migration, apoptosis, adhesion, and angiogenesis through cellular experiments. Additionally, we explored how ARG1 expression levels influenced arginine (Arg), nitric oxide (NO), and ROS levels in HCMEC/D3 cells. The results demonstrated that ARG1 deficiency inhibited HCMEC/D3 cell viability, migration, adhesion, and angiogenesis, while promoting apoptosis and elevating Arg, NO, and ROS levels in HCMEC/D3 cells. Next, the effect of different BBM concentrations on HCMEC/D3 cell viability was assessed using the CCK-8 assay, revealing that BBM at a concentration of 5 µM had no significant impact on cell viability. Subsequently, after successfully knocking down ARG1 in HCMEC/D3 cells, the cells were treated with BBM. The results showed that BBM effectively mitigated the negative effects of ARG1 deficiency on HCMEC/D3 cell viability, migration, apoptosis, adhesion, and angiogenesis, while also reducing Arg, NO, inducible nitric oxide synthase (iNOS), and ROS levels in HCMEC/D3 cells. In conclusion, this study suggests that ARG1 deficiency may damage HCMEC/D3 cells by increasing Arg levels, leading to elevated NO and ROS levels. BBM may provide protection to ARG1-deficient HCMEC/D3 cells by reducing Arg, NO, iNOS, and ROS levels. These findings deepen our understanding of the pathogenesis of CSVD and provide a theoretical basis for the clinical application of BBM. |
| format | Article |
| id | doaj-art-b214a464e56f4e05a686c00f495b8fbc |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-b214a464e56f4e05a686c00f495b8fbc2025-01-09T06:11:09ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.14979731497973Protective effects of berbamine against arginase-1 deficiency-induced injury in human brain microvascular endothelial cellsXiaolan Wei0Weiwei Li1Zixuan Chen2Jintu Chen3Yun Chen4Jiangping Cai5Huasong Lin6Department of Neurology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, ChinaDepartment of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, ChinaDepartment of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, ChinaDepartment of Neurology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, ChinaDepartment of Neurology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, ChinaDepartment of Geriatric Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, ChinaEndothelial cell dysfunction plays a crucial role in the early development of cerebral small vessel disease (CSVD). Arginase-1 (ARG1) is expressed in endothelial cells, and its deficiency may exacerbate cerebrovascular damage by increasing reactive oxygen species (ROS) production, thereby inducing endothelial cell apoptosis. Berbamine (BBM) has shown potential in neuroprotection and cardiovascular disease prevention. This study aimed to investigate the impact of ARG1 deficiency on human brain microvascular endothelial cells and the protective effects of BBM against ARG1 deficiency-induced damage. Human brain microvascular endothelial cells (HCMEC/D3) were cultured in vitro, and ARG1 knockdown or overexpression was achieved using plasmid transfection techniques. We examined the effects of ARG1 expression levels on HCMEC/D3 cell viability, migration, apoptosis, adhesion, and angiogenesis through cellular experiments. Additionally, we explored how ARG1 expression levels influenced arginine (Arg), nitric oxide (NO), and ROS levels in HCMEC/D3 cells. The results demonstrated that ARG1 deficiency inhibited HCMEC/D3 cell viability, migration, adhesion, and angiogenesis, while promoting apoptosis and elevating Arg, NO, and ROS levels in HCMEC/D3 cells. Next, the effect of different BBM concentrations on HCMEC/D3 cell viability was assessed using the CCK-8 assay, revealing that BBM at a concentration of 5 µM had no significant impact on cell viability. Subsequently, after successfully knocking down ARG1 in HCMEC/D3 cells, the cells were treated with BBM. The results showed that BBM effectively mitigated the negative effects of ARG1 deficiency on HCMEC/D3 cell viability, migration, apoptosis, adhesion, and angiogenesis, while also reducing Arg, NO, inducible nitric oxide synthase (iNOS), and ROS levels in HCMEC/D3 cells. In conclusion, this study suggests that ARG1 deficiency may damage HCMEC/D3 cells by increasing Arg levels, leading to elevated NO and ROS levels. BBM may provide protection to ARG1-deficient HCMEC/D3 cells by reducing Arg, NO, iNOS, and ROS levels. These findings deepen our understanding of the pathogenesis of CSVD and provide a theoretical basis for the clinical application of BBM.https://www.frontiersin.org/articles/10.3389/fphar.2024.1497973/fullcerebral small vessel diseasearginase 1arginineberbaminehuman brain microvascular endothelial cells |
| spellingShingle | Xiaolan Wei Weiwei Li Zixuan Chen Jintu Chen Yun Chen Jiangping Cai Huasong Lin Protective effects of berbamine against arginase-1 deficiency-induced injury in human brain microvascular endothelial cells Frontiers in Pharmacology cerebral small vessel disease arginase 1 arginine berbamine human brain microvascular endothelial cells |
| title | Protective effects of berbamine against arginase-1 deficiency-induced injury in human brain microvascular endothelial cells |
| title_full | Protective effects of berbamine against arginase-1 deficiency-induced injury in human brain microvascular endothelial cells |
| title_fullStr | Protective effects of berbamine against arginase-1 deficiency-induced injury in human brain microvascular endothelial cells |
| title_full_unstemmed | Protective effects of berbamine against arginase-1 deficiency-induced injury in human brain microvascular endothelial cells |
| title_short | Protective effects of berbamine against arginase-1 deficiency-induced injury in human brain microvascular endothelial cells |
| title_sort | protective effects of berbamine against arginase 1 deficiency induced injury in human brain microvascular endothelial cells |
| topic | cerebral small vessel disease arginase 1 arginine berbamine human brain microvascular endothelial cells |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1497973/full |
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