DMAG, a novel countermeasure for the treatment of thrombocytopenia

Abstract Background Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for thrombocytopenia remain limited. Methods In this study, giemsa staining, phalloidin staining, immunofluorescence and...

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Autores principales:	Jing Lin, Jing Zeng, Sha Liu, Xin Shen, Nan Jiang, Yue-Song Wu, Hong Li, Long Wang, Jian-Ming Wu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	DMAG Megakaryocytes Platelets Network pharmacology Thrombocytopenia Therapeutics. Pharmacology RM1-950 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/494bfa9258a94516a6707f5188aa45a7
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spelling	oai:doaj.org-article:494bfa9258a94516a6707f5188aa45a72021-11-28T12:10:05ZDMAG, a novel countermeasure for the treatment of thrombocytopenia10.1186/s10020-021-00404-11076-15511528-3658https://doaj.org/article/494bfa9258a94516a6707f5188aa45a72021-11-01T00:00:00Zhttps://doi.org/10.1186/s10020-021-00404-1https://doaj.org/toc/1076-1551https://doaj.org/toc/1528-3658Abstract Background Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for thrombocytopenia remain limited. Methods In this study, giemsa staining, phalloidin staining, immunofluorescence and flow cytometry were used to identify the effects of 3,3ʹ-di-O-methylellagic acid 4ʹ-glucoside (DMAG), a natural ellagic acid derived from Sanguisorba officinalis L. (SOL) on megakaryocyte differentiation in HEL cells. Then, thrombocytopenia mice model was constructed by X-ray irradiation to evaluate the therapeutic action of DMAG on thrombocytopenia. Furthermore, the effects of DMAG on platelet function were evaluated by tail bleeding time, platelet aggregation and platelet adhesion assays. Next, network pharmacology approaches were carried out to identify the targets of DMAG. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the underling mechanism of DMAG against thrombocytopenia. Finally, molecular docking simulation, molecular dynamics simulation and western blot analysis were used to explore the relationship between DAMG with its targets. Results DMAG significantly promoted megakaryocyte differentiation of HEL cells. DMAG administration accelerated platelet recovery and megakaryopoiesis, shortened tail bleeding time, strengthened platelet aggregation and adhesion in thrombocytopenia mice. Network pharmacology revealed that ITGA2B, ITGB3, VWF, PLEK, TLR2, BCL2, BCL2L1 and TNF were the core targets of DMAG. GO and KEGG pathway enrichment analyses suggested that the core targets of DMAG were enriched in PI3K–Akt signaling pathway, hematopoietic cell lineage, ECM-receptor interaction and platelet activation. Molecular docking simulation and molecular dynamics simulation further indicated that ITGA2B, ITGB3, PLEK and TLR2 displayed strong binding ability with DMAG. Finally, western blot analysis evidenced that DMAG up-regulated the expression of ITGA2B, ITGB3, VWF, p-Akt and PLEK. Conclusion DMAG plays a critical role in promoting megakaryocytes differentiation and platelets production and might be a promising medicine for the treatment of thrombocytopenia. Graphical AbstractJing LinJing ZengSha LiuXin ShenNan JiangYue-Song WuHong LiLong WangJian-Ming WuBMCarticleDMAGMegakaryocytesPlateletsNetwork pharmacologyThrombocytopeniaTherapeutics. PharmacologyRM1-950BiochemistryQD415-436ENMolecular Medicine, Vol 27, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	DMAG Megakaryocytes Platelets Network pharmacology Thrombocytopenia Therapeutics. Pharmacology RM1-950 Biochemistry QD415-436
spellingShingle	DMAG Megakaryocytes Platelets Network pharmacology Thrombocytopenia Therapeutics. Pharmacology RM1-950 Biochemistry QD415-436 Jing Lin Jing Zeng Sha Liu Xin Shen Nan Jiang Yue-Song Wu Hong Li Long Wang Jian-Ming Wu DMAG, a novel countermeasure for the treatment of thrombocytopenia
description	Abstract Background Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for thrombocytopenia remain limited. Methods In this study, giemsa staining, phalloidin staining, immunofluorescence and flow cytometry were used to identify the effects of 3,3ʹ-di-O-methylellagic acid 4ʹ-glucoside (DMAG), a natural ellagic acid derived from Sanguisorba officinalis L. (SOL) on megakaryocyte differentiation in HEL cells. Then, thrombocytopenia mice model was constructed by X-ray irradiation to evaluate the therapeutic action of DMAG on thrombocytopenia. Furthermore, the effects of DMAG on platelet function were evaluated by tail bleeding time, platelet aggregation and platelet adhesion assays. Next, network pharmacology approaches were carried out to identify the targets of DMAG. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the underling mechanism of DMAG against thrombocytopenia. Finally, molecular docking simulation, molecular dynamics simulation and western blot analysis were used to explore the relationship between DAMG with its targets. Results DMAG significantly promoted megakaryocyte differentiation of HEL cells. DMAG administration accelerated platelet recovery and megakaryopoiesis, shortened tail bleeding time, strengthened platelet aggregation and adhesion in thrombocytopenia mice. Network pharmacology revealed that ITGA2B, ITGB3, VWF, PLEK, TLR2, BCL2, BCL2L1 and TNF were the core targets of DMAG. GO and KEGG pathway enrichment analyses suggested that the core targets of DMAG were enriched in PI3K–Akt signaling pathway, hematopoietic cell lineage, ECM-receptor interaction and platelet activation. Molecular docking simulation and molecular dynamics simulation further indicated that ITGA2B, ITGB3, PLEK and TLR2 displayed strong binding ability with DMAG. Finally, western blot analysis evidenced that DMAG up-regulated the expression of ITGA2B, ITGB3, VWF, p-Akt and PLEK. Conclusion DMAG plays a critical role in promoting megakaryocytes differentiation and platelets production and might be a promising medicine for the treatment of thrombocytopenia. Graphical Abstract
format	article
author	Jing Lin Jing Zeng Sha Liu Xin Shen Nan Jiang Yue-Song Wu Hong Li Long Wang Jian-Ming Wu
author_facet	Jing Lin Jing Zeng Sha Liu Xin Shen Nan Jiang Yue-Song Wu Hong Li Long Wang Jian-Ming Wu
author_sort	Jing Lin
title	DMAG, a novel countermeasure for the treatment of thrombocytopenia
title_short	DMAG, a novel countermeasure for the treatment of thrombocytopenia
title_full	DMAG, a novel countermeasure for the treatment of thrombocytopenia
title_fullStr	DMAG, a novel countermeasure for the treatment of thrombocytopenia
title_full_unstemmed	DMAG, a novel countermeasure for the treatment of thrombocytopenia
title_sort	dmag, a novel countermeasure for the treatment of thrombocytopenia
publisher	BMC
publishDate	2021
url	https://doaj.org/article/494bfa9258a94516a6707f5188aa45a7
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DMAG, a novel countermeasure for the treatment of thrombocytopenia

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