Qilong capsule alleviates ponatinib-induced ischemic stroke in a zebrafish model by regulating coagulation, inflammation and apoptosis

Lin, Shenghua; Liu, Xin; Sun, Aonan; Liang, Huiliang; Li, Zhen; Ye, Suyan; Ma, Honglin; Wang, Fan; Shen, Chuanlin; Meng, J.; He, Qiuxia

doi:10.1016/j.jep.2023.116397

Cited by 7 publications

(3 citation statements)

References 22 publications

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“…During further investigations, the results of our Western blot assay confirmed that the observed changes are the consequence of the EC apoptosis-inducing effect of this drug, as ponatinib increased the ratio of Bax and Bcl-xL proteins. This result was also supported by the findings of other investigators that were observed in a zebrafish model [29]. In our study, the TNF-α treatment increased the PS expression, enhanced the formation of EMVs, resulted in earlier and enhanced thrombin generation, and also increased the ratio of Bax/Bcl-xL.…”

Section: Discussionsupporting

confidence: 93%

Ponatinib Induces a Procoagulant Phenotype in Human Coronary Endothelial Cells via Inducing Apoptosis

Krajcsir,

Pócsi,

Fejes

et al. 2024

Pharmaceutics

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BCR-ABL tyrosine kinase inhibitors (TKIs) are effective drugs in the treatment of patients with chronic myeloid leukemia. However, based on clinical studies, ponatinib was associated with the development of thrombotic complications. Since endothelial cells (ECs) regulate blood coagulation, their abnormal phenotype may play a role in the development of thrombotic events. We here aimed to investigate the effect of ponatinib on the procoagulant activity of cultured endothelial cells in vitro. Human coronary artery endothelial cells (HCAECs) were incubated with 50, 150, and 1000 nM of ponatinib. Subsequently, phosphatidylserine (PS) exposure and endothelial microvesicles (EMVs) were measured by flow cytometry. In addition, EC- and EMV-dependent thrombin generation was analyzed. To investigate pro-apoptotic effects of ponatinib, the level of Bax and Bcl-xL proteins were studied using Western blot and F3, THBD, and VCAM1 mRNAs were quantified by qPCR. Therapeutic concentrations of ponatinib significantly increased PS expression on ECs and the amount of EMVs which significantly shortened the time parameters of thrombin generation. In addition, these changes were associated with an increased ratio of Bax and Bcl-xL proteins in the presence of the decreased THBD mRNA level. Overall, ponatinib enhances the procoagulant activity of ECs via inducing apoptosis, which may contribute to thrombotic events.

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Section: Discussionsupporting

confidence: 93%

Ponatinib Induces a Procoagulant Phenotype in Human Coronary Endothelial Cells via Inducing Apoptosis

Krajcsir,

Pócsi,

Fejes

et al. 2024

Pharmaceutics

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“…After the zebrafish had been incubated with a combination of pae, diosmetin-7- O -glucoside, and 5-HMF, we then used o-dianisidine to stain the red blood cells in order to visualize thrombosis ( Lin et al, 2023 ). First, we aspirated the culture media from the culture dish and added 1 mL of the o-dianisidine dye solution.…”

Section: Methodsmentioning

confidence: 99%

“…Following RT-qPCR, the CT value for each group was determined with LightCycler 96 SW 1.1 software. The 2 −ΔΔCT method was used to determine the relative gene expression ( Lin et al, 2023 ). The sequences of the primers used in this part of the study are shown in Supplementary Table S1 .…”

Section: Methodsmentioning

confidence: 99%

The combination of paeonol, diosmetin-7-O-β-D-glucopyranoside, and 5-hydroxymethylfurfural from Trichosanthis pericarpium alleviates arachidonic acid-induced thrombosis in a zebrafish model

Lin,

Ma,

Zhang

et al. 2024

Front. Pharmacol.

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Trichosanthis fruit (TF) is a classic medicinal material obtained from Shandong, China. The peel of this fruit (Trichosanthis pericarpium, TP) is known to exert anti-thrombotic effects. However, the anti-thrombotic active components and mechanisms of TP have yet to be fully elucidated. Combined with zebrafish models and high-performance liquid chromatography (HPLC), this study evaluated the endogenous anti-thrombotic effects with the combination of three compounds from TP. First, we used HPLC to investigate the components in the water extract of TP. Next, we used the zebrafish model to investigate the anti-thrombotic activity of the three compound combinations by evaluating a range of indicators. Finally, the expression of related genes was detected by real-time quantitative polymerase chain reaction (qPCR). HPLC detected a total of eight components in TP water extract, with high levels of paeonol (Pae), diosmetin-7-O-β-D-glucopyranoside (diosmetin-7-O-glucoside), and 5-hydroxymethylfurfural (5-HMF). The most significant anti-thrombotic activity was detected when the Pae: diosmetin-7-O-glucoside:5-HMF ratio was 4:3:3. qPCR analysis revealed that the abnormal expression levels of f2, fga, fgb, vwf, ptgs1, and tbxas1 induced by arachidonic acid (AA) were improved. The combination of Pae, diosmetin-7-O-glucoside, and 5-HMF may alleviate AA-induced thrombosis by inhibiting the inflammatory reaction, coagulation cascade reaction, and arachidonic acid metabolism pathways.

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APMCG-1 attenuates ischemic stroke injury by reducing oxidative stress and apoptosis and promoting angiogenesis via activating PI3K/AKT pathway

He,

Wu,

Chen

et al. 2024

Biomedicine & Pharmacotherapy

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Qilong capsule alleviates ponatinib-induced ischemic stroke in a zebrafish model by regulating coagulation, inflammation and apoptosis

Cited by 7 publications

References 22 publications

Ponatinib Induces a Procoagulant Phenotype in Human Coronary Endothelial Cells via Inducing Apoptosis

Ponatinib Induces a Procoagulant Phenotype in Human Coronary Endothelial Cells via Inducing Apoptosis

The combination of paeonol, diosmetin-7-O-β-D-glucopyranoside, and 5-hydroxymethylfurfural from Trichosanthis pericarpium alleviates arachidonic acid-induced thrombosis in a zebrafish model

APMCG-1 attenuates ischemic stroke injury by reducing oxidative stress and apoptosis and promoting angiogenesis via activating PI3K/AKT pathway

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