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Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis
Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo. M...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644720/ https://www.ncbi.nlm.nih.gov/pubmed/38026984 http://dx.doi.org/10.3389/fphar.2023.1255069 |
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author | Ye, Yujia Yang, Lihong Leng, Min Wang, Qian Wu, Jiankui Wan, Wen Wang, Huawei Li, Longjun Peng, Yunzhu Chai, Shengjie Meng, Zhaohui |
author_facet | Ye, Yujia Yang, Lihong Leng, Min Wang, Qian Wu, Jiankui Wan, Wen Wang, Huawei Li, Longjun Peng, Yunzhu Chai, Shengjie Meng, Zhaohui |
author_sort | Ye, Yujia |
collection | PubMed |
description | Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo. Methods: Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca(2+), and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR). Results: Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbβ3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagen- adrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress in vivo. Luteolin did not affect coagulation, hemostasis, or platelet production in mice. Discussion: Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified. |
format | Online Article Text |
id | pubmed-10644720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106447202023-10-31 Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis Ye, Yujia Yang, Lihong Leng, Min Wang, Qian Wu, Jiankui Wan, Wen Wang, Huawei Li, Longjun Peng, Yunzhu Chai, Shengjie Meng, Zhaohui Front Pharmacol Pharmacology Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo. Methods: Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca(2+), and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR). Results: Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbβ3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagen- adrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress in vivo. Luteolin did not affect coagulation, hemostasis, or platelet production in mice. Discussion: Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified. Frontiers Media S.A. 2023-10-31 /pmc/articles/PMC10644720/ /pubmed/38026984 http://dx.doi.org/10.3389/fphar.2023.1255069 Text en Copyright © 2023 Ye, Yang, Leng, Wang, Wu, Wan, Wang, Li, Peng, Chai and Meng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Ye, Yujia Yang, Lihong Leng, Min Wang, Qian Wu, Jiankui Wan, Wen Wang, Huawei Li, Longjun Peng, Yunzhu Chai, Shengjie Meng, Zhaohui Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis |
title | Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis |
title_full | Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis |
title_fullStr | Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis |
title_full_unstemmed | Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis |
title_short | Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis |
title_sort | luteolin inhibits gpvi-mediated platelet activation, oxidative stress, and thrombosis |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644720/ https://www.ncbi.nlm.nih.gov/pubmed/38026984 http://dx.doi.org/10.3389/fphar.2023.1255069 |
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