Identification of the Antithrombotic Mechanism of Leonurine in Adrenalin Hydrochloride-Induced Thrombosis in Zebrafish via Regulating Oxidative Stress and Coagulation Cascade
Thrombosis is a general pathological phenomenon during severe disturbances to homeostasis, which plays an essential role in cardiovascular and cerebrovascular diseases. Leonurine (LEO), isolated from Leonurus japonicus Houtt, showes a crucial role in anticoagulation and vasodilatation. However, the...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:5eb5ec3ce9b6441c9f965cad4f515ab42021-11-04T06:54:18ZIdentification of the Antithrombotic Mechanism of Leonurine in Adrenalin Hydrochloride-Induced Thrombosis in Zebrafish via Regulating Oxidative Stress and Coagulation Cascade1663-981210.3389/fphar.2021.742954https://doaj.org/article/5eb5ec3ce9b6441c9f965cad4f515ab42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.742954/fullhttps://doaj.org/toc/1663-9812Thrombosis is a general pathological phenomenon during severe disturbances to homeostasis, which plays an essential role in cardiovascular and cerebrovascular diseases. Leonurine (LEO), isolated from Leonurus japonicus Houtt, showes a crucial role in anticoagulation and vasodilatation. However, the properties and therapeutic mechanisms of this effect have not yet been systematically elucidated. Therefore, the antithrombotic effect of LEO was investigated in this study. Hematoxylin-Eosin staining was used to detect the thrombosis of zebrafish tail. Fluorescence probe was used to detect the reactive oxygen species. The biochemical indexes related to oxidative stress (lactate dehydrogenase, malondialdehyde, superoxide dismutase and glutathione) and vasodilator factor (endothelin-1 and nitric oxide) were analyzed by specific commercial assay kits. Besides, we detected the expression of related genes (fga, fgb, fgg, pkcα, pkcβ, vwf, f2) and proteins (PI3K, phospho-PI3K, Akt, phospho-Akt, ERK, phospho-ERK FIB) related to the anticoagulation and fibrinolytic system by quantitative reverse transcription and western blot. Beyond that, metabolomic analyses were carried out to identify the expressions of metabolites associated with the anti-thrombosis mechanism of LEO. Our in vivo experimental results showed that LEO could improve the oxidative stress injury, abnormal platelet aggregation and coagulation dysfunction induced by adrenalin hydrochloride. Moreover, LEO restored the modulation of amino acids and inositol metabolites which are reported to alleviate the thrombus formation. Collectively, LEO attenuates adrenalin hydrochloride-induced thrombosis partly via modulating oxidative stress, coagulation cascade and platelet activation and amino acid and inositol metabolites.Li LiaoLi LiaoLi LiaoMengting ZhouMengting ZhouMengting ZhouJing WangJing WangJing WangXinyan XueXinyan XueXinyan XueYing DengYing DengYing DengXingtao ZhaoXingtao ZhaoXingtao ZhaoCheng PengCheng PengCheng PengYunxia LiYunxia LiYunxia LiFrontiers Media S.A.articlethrombosisleonurineoxidative stresscoagulation cascademetabolomic analysisTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
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thrombosis leonurine oxidative stress coagulation cascade metabolomic analysis Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
thrombosis leonurine oxidative stress coagulation cascade metabolomic analysis Therapeutics. Pharmacology RM1-950 Li Liao Li Liao Li Liao Mengting Zhou Mengting Zhou Mengting Zhou Jing Wang Jing Wang Jing Wang Xinyan Xue Xinyan Xue Xinyan Xue Ying Deng Ying Deng Ying Deng Xingtao Zhao Xingtao Zhao Xingtao Zhao Cheng Peng Cheng Peng Cheng Peng Yunxia Li Yunxia Li Yunxia Li Identification of the Antithrombotic Mechanism of Leonurine in Adrenalin Hydrochloride-Induced Thrombosis in Zebrafish via Regulating Oxidative Stress and Coagulation Cascade |
| description |
Thrombosis is a general pathological phenomenon during severe disturbances to homeostasis, which plays an essential role in cardiovascular and cerebrovascular diseases. Leonurine (LEO), isolated from Leonurus japonicus Houtt, showes a crucial role in anticoagulation and vasodilatation. However, the properties and therapeutic mechanisms of this effect have not yet been systematically elucidated. Therefore, the antithrombotic effect of LEO was investigated in this study. Hematoxylin-Eosin staining was used to detect the thrombosis of zebrafish tail. Fluorescence probe was used to detect the reactive oxygen species. The biochemical indexes related to oxidative stress (lactate dehydrogenase, malondialdehyde, superoxide dismutase and glutathione) and vasodilator factor (endothelin-1 and nitric oxide) were analyzed by specific commercial assay kits. Besides, we detected the expression of related genes (fga, fgb, fgg, pkcα, pkcβ, vwf, f2) and proteins (PI3K, phospho-PI3K, Akt, phospho-Akt, ERK, phospho-ERK FIB) related to the anticoagulation and fibrinolytic system by quantitative reverse transcription and western blot. Beyond that, metabolomic analyses were carried out to identify the expressions of metabolites associated with the anti-thrombosis mechanism of LEO. Our in vivo experimental results showed that LEO could improve the oxidative stress injury, abnormal platelet aggregation and coagulation dysfunction induced by adrenalin hydrochloride. Moreover, LEO restored the modulation of amino acids and inositol metabolites which are reported to alleviate the thrombus formation. Collectively, LEO attenuates adrenalin hydrochloride-induced thrombosis partly via modulating oxidative stress, coagulation cascade and platelet activation and amino acid and inositol metabolites. |
| format |
article |
| author |
Li Liao Li Liao Li Liao Mengting Zhou Mengting Zhou Mengting Zhou Jing Wang Jing Wang Jing Wang Xinyan Xue Xinyan Xue Xinyan Xue Ying Deng Ying Deng Ying Deng Xingtao Zhao Xingtao Zhao Xingtao Zhao Cheng Peng Cheng Peng Cheng Peng Yunxia Li Yunxia Li Yunxia Li |
| author_facet |
Li Liao Li Liao Li Liao Mengting Zhou Mengting Zhou Mengting Zhou Jing Wang Jing Wang Jing Wang Xinyan Xue Xinyan Xue Xinyan Xue Ying Deng Ying Deng Ying Deng Xingtao Zhao Xingtao Zhao Xingtao Zhao Cheng Peng Cheng Peng Cheng Peng Yunxia Li Yunxia Li Yunxia Li |
| author_sort |
Li Liao |
| title |
Identification of the Antithrombotic Mechanism of Leonurine in Adrenalin Hydrochloride-Induced Thrombosis in Zebrafish via Regulating Oxidative Stress and Coagulation Cascade |
| title_short |
Identification of the Antithrombotic Mechanism of Leonurine in Adrenalin Hydrochloride-Induced Thrombosis in Zebrafish via Regulating Oxidative Stress and Coagulation Cascade |
| title_full |
Identification of the Antithrombotic Mechanism of Leonurine in Adrenalin Hydrochloride-Induced Thrombosis in Zebrafish via Regulating Oxidative Stress and Coagulation Cascade |
| title_fullStr |
Identification of the Antithrombotic Mechanism of Leonurine in Adrenalin Hydrochloride-Induced Thrombosis in Zebrafish via Regulating Oxidative Stress and Coagulation Cascade |
| title_full_unstemmed |
Identification of the Antithrombotic Mechanism of Leonurine in Adrenalin Hydrochloride-Induced Thrombosis in Zebrafish via Regulating Oxidative Stress and Coagulation Cascade |
| title_sort |
identification of the antithrombotic mechanism of leonurine in adrenalin hydrochloride-induced thrombosis in zebrafish via regulating oxidative stress and coagulation cascade |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/5eb5ec3ce9b6441c9f965cad4f515ab4 |
| work_keys_str_mv |
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