Integrated Transcriptomics and Reverse Pharmacophore Mapping-based Network Pharmacology to Explore the Mechanisms of Natural Compounds against Doxorubicin-induced Cardiotoxicity

doi:10.2174/1386207324666210816122629

	Integrated Transcriptomics and Reverse Pharmacophore Mapping-based Network Pharmacology to Explore the Mechanisms of Natural Compounds against Doxorubicin-induced Cardiotoxicity
	Zhu, Junfeng 1; Yi, Xiaojiao 2; Ding, Haiying 1; Zhong, Like 1; Fang, Luo 1
刊名	COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
	2022
卷号	25
关键词	Doxorubicin-induced cardiotoxicity natural compounds mechanism of action gene expression profile bioinformatics network pharmacology
ISSN号	1386-2073
DOI	10.2174/1386207324666210816122629
通讯作者	Fang, Luo(fangluo@zjcc.org.cn)
英文摘要	Background: Doxorubicin-Induced Cardiotoxicity (DIC) has greatly limited the clinical benefits of this frontline drug in oncotherapy. Drug combination with Natural Compounds (NCs) that possess potency against DIC is considered as a promising intervention strategy. However, the Mechanisms of Action (MoAs) underlying such drug interactions remain poorly understood. The aim of this study was to systematically pursuit of the molecular mechanisms of NCs against DIC. Methods: First, the gene expression signatures of DIC were characterized from transcriptomics datasets with doxorubicin-treated and untreated cardiomyocytes using differentially expressed gene identification, functional enrichment analysis, and protein-protein interaction network analysis. Secondly, reverse pharmacophore mapping-based network pharmacology was employed to illustrate the MoAs of 82 publicly reported NCs with anti-DIC potency. Cluster analysis based on their enriched pathways was performed to gain systematic insights into the anti-DIC mechanisms of the NCs. Finally, the typical compounds were validated using Gene Set Enrichment Analysis (GSEA) of the relevant gene expression profiles from a public gene expression database. Results: Based on their anti-DIC MoAs, the 82 NCs could be divided into four groups, which corresponded to ten MoA clusters. GSEA and literature evidence on these compounds were provided to validate the MoAs identified through this bioinformatics analysis. The results suggested that NCs exerted potency against DIC through both common and different MoAs. Conclusion: This strategy integrating different types of bioinformatics approaches is expected to create new insights for elucidating the MoAs of NCs against DIC.
资助项目	National Natural Science Foundation of China[82003920] ; Zhejiang Provincial Natural Science Foundation of China[LQ19H280002] ; Zhejiang Provincial Project of Medical and Health Technology[2020KY457] ; Zhejiang Provincial Project of Traditional Chinese Medicine Science and Technology[2021ZB040] ; University of Chinese Academy of Sciences
WOS关键词	ASTRAGALOSIDE IV ; CELLS ; ACTIVATION ; APOPTOSIS ; PROTECTS ; PI3K/AKT ; STRESS ; INJURY ; FOXO
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	BENTHAM SCIENCE PUBL LTD
WOS记录号	WOS:000858443000013
资助机构	National Natural Science Foundation of China ; Zhejiang Provincial Natural Science Foundation of China ; Zhejiang Provincial Project of Medical and Health Technology ; Zhejiang Provincial Project of Traditional Chinese Medicine Science and Technology ; University of Chinese Academy of Sciences
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/129073]
专题	中国科学院合肥物质科学研究院
通讯作者	Fang, Luo
作者单位	1.Chinese Acad Sci, Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp,Inst Basic Med & Canc IBMC, Hangzhou 310022, Peoples R China 2.Xixi Hosp Hangzhou, Dept Pharm, Hangzhou 310023, Peoples R China
推荐引用方式 GB/T 7714	Zhu, Junfeng,Yi, Xiaojiao,Ding, Haiying,et al. Integrated Transcriptomics and Reverse Pharmacophore Mapping-based Network Pharmacology to Explore the Mechanisms of Natural Compounds against Doxorubicin-induced Cardiotoxicity[J]. COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING,2022,25.
APA	Zhu, Junfeng,Yi, Xiaojiao,Ding, Haiying,Zhong, Like,&Fang, Luo.(2022).Integrated Transcriptomics and Reverse Pharmacophore Mapping-based Network Pharmacology to Explore the Mechanisms of Natural Compounds against Doxorubicin-induced Cardiotoxicity.COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING,25.
MLA	Zhu, Junfeng,et al."Integrated Transcriptomics and Reverse Pharmacophore Mapping-based Network Pharmacology to Explore the Mechanisms of Natural Compounds against Doxorubicin-induced Cardiotoxicity".COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING 25(2022).