Biological evaluation of sophoridine by interaction with plasma transport protein and protective effects in cardiomyocytes

Numerous studies have demonstrated the protective benefits of sophoridine, a bioactive alkaloid, on cell damage. However, its primary biological properties such as interaction with plasma protein, which serves as the primary drug carrier, and its cardioprotective properties are still unknown. In the...

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Main Authors: Zheng Wu, Shujuan Cheng, Shaoping Wang, Wenzheng Li, Jinghua Liu
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Arabian Journal of Chemistry
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Online Access:http://www.sciencedirect.com/science/article/pii/S1878535224004167
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author Zheng Wu
Shujuan Cheng
Shaoping Wang
Wenzheng Li
Jinghua Liu
author_facet Zheng Wu
Shujuan Cheng
Shaoping Wang
Wenzheng Li
Jinghua Liu
author_sort Zheng Wu
collection DOAJ
description Numerous studies have demonstrated the protective benefits of sophoridine, a bioactive alkaloid, on cell damage. However, its primary biological properties such as interaction with plasma protein, which serves as the primary drug carrier, and its cardioprotective properties are still unknown. In the present study, we aimed to analyze the binding characteristics of sophoridine with alpha-2-macroglobulin (α2M) by spectroscopic and theoretical studies. Then, the cardioprotective effects of sophoridine on myocardial ischemia/reperfusion (MI/R) injury in vitro were investigated using H9c2 cardiomyocytes. The results reveal that one molecule of sophoridine favorably binds to one molecule of α2M dominantly through interaction with hydrophobic amino acid residues (VAL758, PHE735, PHE735, and TRP739). Also, sophoridine leads to partial changes in the structure of this carrier protein in the vicinity of TRP739 residue. Cellular assays exhibit that sophoridine recovered cell viability, membrane leakage, and apoptosis induced by MI/R injury. It was detected that sophoridine could mitigate the oxidative stress and intrinsic apoptosis pathway through regulation of Bax, Bcl-2, and caspase. ELISA analysis also exhibits that sophoridine upregulates phosphorylation of Akt and PI3K in H9c2 cells. Our findings suggest that sophoridine could show favorable plasma protein interaction and promising cardioprotection against MI/R injury mediated by the upregulation of PI3K/AKT signaling pathway.
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spelling doaj-art-3fc25e52d27648ffb3bbd65cb76c2b9c2024-11-18T04:32:42ZengElsevierArabian Journal of Chemistry1878-53522024-12-011712106014Biological evaluation of sophoridine by interaction with plasma transport protein and protective effects in cardiomyocytesZheng Wu0Shujuan Cheng1Shaoping Wang2Wenzheng Li3Jinghua Liu4Department of 28 Division of Cardiovascular, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of 28 Division of Cardiovascular, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of 28 Division of Cardiovascular, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of 28 Division of Cardiovascular, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaCorresponding author at: Department of 28 Division of Cardiovascular, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, No. 2, Anzhen Road, Beijing 100029, China.; Department of 28 Division of Cardiovascular, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaNumerous studies have demonstrated the protective benefits of sophoridine, a bioactive alkaloid, on cell damage. However, its primary biological properties such as interaction with plasma protein, which serves as the primary drug carrier, and its cardioprotective properties are still unknown. In the present study, we aimed to analyze the binding characteristics of sophoridine with alpha-2-macroglobulin (α2M) by spectroscopic and theoretical studies. Then, the cardioprotective effects of sophoridine on myocardial ischemia/reperfusion (MI/R) injury in vitro were investigated using H9c2 cardiomyocytes. The results reveal that one molecule of sophoridine favorably binds to one molecule of α2M dominantly through interaction with hydrophobic amino acid residues (VAL758, PHE735, PHE735, and TRP739). Also, sophoridine leads to partial changes in the structure of this carrier protein in the vicinity of TRP739 residue. Cellular assays exhibit that sophoridine recovered cell viability, membrane leakage, and apoptosis induced by MI/R injury. It was detected that sophoridine could mitigate the oxidative stress and intrinsic apoptosis pathway through regulation of Bax, Bcl-2, and caspase. ELISA analysis also exhibits that sophoridine upregulates phosphorylation of Akt and PI3K in H9c2 cells. Our findings suggest that sophoridine could show favorable plasma protein interaction and promising cardioprotection against MI/R injury mediated by the upregulation of PI3K/AKT signaling pathway.http://www.sciencedirect.com/science/article/pii/S1878535224004167SophoridineAlpha-2-macroglobulinCardioprotective effect
spellingShingle Zheng Wu
Shujuan Cheng
Shaoping Wang
Wenzheng Li
Jinghua Liu
Biological evaluation of sophoridine by interaction with plasma transport protein and protective effects in cardiomyocytes
Arabian Journal of Chemistry
Sophoridine
Alpha-2-macroglobulin
Cardioprotective effect
title Biological evaluation of sophoridine by interaction with plasma transport protein and protective effects in cardiomyocytes
title_full Biological evaluation of sophoridine by interaction with plasma transport protein and protective effects in cardiomyocytes
title_fullStr Biological evaluation of sophoridine by interaction with plasma transport protein and protective effects in cardiomyocytes
title_full_unstemmed Biological evaluation of sophoridine by interaction with plasma transport protein and protective effects in cardiomyocytes
title_short Biological evaluation of sophoridine by interaction with plasma transport protein and protective effects in cardiomyocytes
title_sort biological evaluation of sophoridine by interaction with plasma transport protein and protective effects in cardiomyocytes
topic Sophoridine
Alpha-2-macroglobulin
Cardioprotective effect
url http://www.sciencedirect.com/science/article/pii/S1878535224004167
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AT shaopingwang biologicalevaluationofsophoridinebyinteractionwithplasmatransportproteinandprotectiveeffectsincardiomyocytes
AT wenzhengli biologicalevaluationofsophoridinebyinteractionwithplasmatransportproteinandprotectiveeffectsincardiomyocytes
AT jinghualiu biologicalevaluationofsophoridinebyinteractionwithplasmatransportproteinandprotectiveeffectsincardiomyocytes