Trilobatin promotes angiogenesis after cerebral ischemia–reperfusion injury via SIRT7/VEGFA signaling pathway in rats
Angiogenesis plays a pivotal role in the recovery of neurological function after ischemia stroke. Herein, we investigated the effect of trilobatin (TLB) on angiogenesis after cerebral ischemia–reperfusion injury (CIRI). The effect of TLB on angiogenesis after CIRI were investigated in mouse brain mi...
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Published in | Phytotherapy research Vol. 36; no. 7; pp. 2940 - 2951 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Chichester, UK
John Wiley & Sons, Ltd
01.07.2022
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Angiogenesis plays a pivotal role in the recovery of neurological function after ischemia stroke. Herein, we investigated the effect of trilobatin (TLB) on angiogenesis after cerebral ischemia–reperfusion injury (CIRI). The effect of TLB on angiogenesis after CIRI were investigated in mouse brain microvascular endothelium bEnd.3 cells and middle cerebral artery occlusion (MCAO)‐induced CIRI rat model. The cell proliferation and angiogenesis were observed using immunofluorescence staining. The cell cycle, expressions of cell cycle‐related proteins and SIRT 1–7 were determined by flow cytometry and western blot, respectively. The binding affinity of TLB with SIRT7 was predicted by molecular docking. The results showed that TLB concentration‐dependently promoted bEnd.3 cell proportion in the S‐phase. TLB significantly increased the protein expressions of SIRT6, SIRT7, and VEGFA, but not affected SIRT1‐SIRT5 protein expressions. Moreover, TLB not only dramatically alleviated neurological impairment after CIRI, but also enhanced post‐stroke neovascularization and newly formed functional vessels in cerebral ischemic penumbra. Furthermore, TLB up‐regulated the protein expressions of CDK4, cyclin D1, VEGFA and its receptor VEGFR‐2. Intriguingly, TLB not only directly bound to SIRT7, but also increased SIRT7 expression at day 28. Our findings reveal that TLB promotes cerebral microvascular endothelial cells proliferation, and facilitates angiogenesis after CIRI via mediating SIRT7/VEGFA signaling pathway in rats. Therefore, TLB might be a novel restorative agent to rescue ischemia stroke. |
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Bibliography: | Funding information Lithocarpus ploystachyus Reld. sweet tea in Zunyi city, Grant/Award Number: technology talents[2021]4; National key R & D plan for Research on modernization of Traditional Chinese Medicine, Grant/Award Number: 2017YFC1702005; Post subsidy project of State key R & D plan in social development field, Grant/Award Number: SQ2017YFC170204‐05; Program for Changjiang Scholars and Innovative Research Team in University, China, Grant/Award Number: IRT_17R113; Program for Outstanding Youth of Zunyi Medical University, Grant/Award Number: 15zy‐002; Science and Technology Support Plan of Guizhou Province, Grant/Award Number: Supporting Science and Technology Cooperation of Guizhou Province [2020]1Y010 Innovative Research Team of comprehensive utilization with ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0951-418X 1099-1573 |
DOI: | 10.1002/ptr.7487 |