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 |
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Chichester, UK
John Wiley & Sons, Ltd
01.07.2022
Wiley Subscription Services, Inc |
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Abstract | 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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AbstractList | Abstract
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. 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. |
Author | Wu, Yujia Luo, Lingyu Xu, Fan Gong, Qihai Xia, Dianya Huang, Fengying Gao, Jianmei Shi, Jingshan |
Author_xml | – sequence: 1 givenname: Fengying surname: Huang fullname: Huang, Fengying organization: Zunyi Medical University – sequence: 2 givenname: Lingyu surname: Luo fullname: Luo, Lingyu organization: Zunyi Medical University – sequence: 3 givenname: Yujia surname: Wu fullname: Wu, Yujia organization: Zunyi Medical University – sequence: 4 givenname: Dianya surname: Xia fullname: Xia, Dianya organization: Zunyi Medical University – sequence: 5 givenname: Fan surname: Xu fullname: Xu, Fan organization: Albert‐Ludwigs‐University Freiburg – sequence: 6 givenname: Jianmei surname: Gao fullname: Gao, Jianmei organization: Zunyi Medical University – sequence: 7 givenname: Jingshan surname: Shi fullname: Shi, Jingshan organization: Zunyi Medical University – sequence: 8 givenname: Qihai orcidid: 0000-0002-8967-337X surname: Gong fullname: Gong, Qihai email: gqh@zmu.edu.cn organization: Zunyi Medical University |
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Snippet | Angiogenesis plays a pivotal role in the recovery of neurological function after ischemia stroke. Herein, we investigated the effect of trilobatin (TLB) on... Abstract Angiogenesis plays a pivotal role in the recovery of neurological function after ischemia stroke. Herein, we investigated the effect of trilobatin... |
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SubjectTerms | Angiogenesis Cell cycle Cell proliferation Cerebral blood flow cerebral ischemia Cyclin D1 Endothelial cells Endothelium Flow cytometry Immunofluorescence Ischemia Microvasculature Molecular docking Neurological complications Occlusion Proteins Reperfusion Signal transduction Signaling silent information regulator 7 SIRT1 protein Stroke trilobatin Vascular endothelial growth factor receptors Vascularization |
Title | Trilobatin promotes angiogenesis after cerebral ischemia–reperfusion injury via SIRT7/VEGFA signaling pathway in rats |
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