| Status | 已發表Published |
| Tetramethylpyrazine nitrone (TBN), derivative from traditional Chinese medicine Chuan Xiong exerted a protective effect on neurovascular unit against mural amyloid-beta1-42 oligomers | |
Qian, E. ; Hoi, P. M.
| |
| 2021-04-09 | |
| Source Publication | Medicinal and Food Plant Research & Natural Products and Biodiversity Resources
 |
| Abstract | Objective: Disruption of blood brain barrier (BBB) has been acknowledged to be related to the progression of Alzheimer’s disease (AD). Meanwhile, increasing evidence has shown that diffusible and soluble amyloid beta 1-42 (Aβ1-42) oligomer in brain accounts for BBB disruption in AD. TBN, derivative of Ligusticum wallichii (Chuanxiong) has been widely investigated for its anti-AD effects. Herein, we employed bEnd.3 cell and C8-D1A cell to investigate the effect of TBN on Aβ1-42-induced damage in neurovascular unit. Materials and Methods: mouse brain endothelial cell line (bEnd.3) and mouse astrocyte cell line (C8-D1A) were employed. bEnd.3 monolayer model in transwell was established. Soluble Aβ1-42 oligomer (sAβ1-42O) was prepared as inducer. Cell viability and ROS production were assessed by MTT and DCFDA assays. Barrier function was evaluated by transendothelial electrical resistance (TEER) and permeability of immunofluorescent tracer (FITC-dextran). Levels of endothelial junction proteins (ZO-1, Claudin-5) were further evaluated by western blot and immunofluorescent staining. Results: TBN showed no toxic effect on bEnd.3 and C8-D1A cell. It protected against sAβ1-42O-induced cytotoxicity in bEnd.3 and C8-D1A. TBN improved barrier functions of bEnd.3 monolayer against sAβ1-42O-induced damage (elevated TEER value and decreased permeability). Level of Claudin-5 and ZO-1 were upregulated by TBN. The underlying mechanism maybe related to eNOS. Furthermore, TBN inhibited astrocytic Bcl-2/Bax/caspase-3, p-VEGFR2/VEGFR2 and activated pErk/Erk in a dose-dependent manner. TBN attenuated sAβ1-42O-induced astrocyte activation (decrease of ROS production). Upregulation of iNOS, TLR4 and downregulation of pErk/Erk were reversed by TBN. Conclusion: TBN protected bEnd.3 integrity and barrier function against the damage of sAβ1-42O by upregulating the level of tight junctions. Meanwhile, it attenuated sAβ1-42O induced astrocyte activation. It can be concluded that TBN could protect neurovascular unit against sAβ1-42O induced damage. |
| Keyword | TCM neurovascular unit amyloid beta |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 59482 |
| Document Type | Conference paper |
| Collection | Institute of Chinese Medical Sciences |
| Recommended Citation GB/T 7714 | Qian, E.,Hoi, P. M.. Tetramethylpyrazine nitrone (TBN), derivative from traditional Chinese medicine Chuan Xiong exerted a protective effect on neurovascular unit against mural amyloid-beta1-42 oligomers[C], 2021. |
| APA | Qian, E.., & Hoi, P. M. (2021). Tetramethylpyrazine nitrone (TBN), derivative from traditional Chinese medicine Chuan Xiong exerted a protective effect on neurovascular unit against mural amyloid-beta1-42 oligomers. Medicinal and Food Plant Research & Natural Products and Biodiversity Resources. |
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