数字中医药（英文）2021，Vol.4Issue(4)：328-342,15.DOI:10.1016/j.dcmed.2021.12.007
基于网络药理学和代谢组学的复方阿胶浆抗再生障碍性贫血研究
Protective effects of Fufang Ejiao Jiang against aplastic anemia assessed by network pharmacology and metabolomics strategy
摘要
Abstract
Objective To elucidate the mechanisms underlying the thera-peutic effects of Fufang Ejiao Jiang (复方阿胶浆,FFEJJ) on aplastic anemia (AA) using integrated network pharmacology and serum metabolomics.Methods Traditional Chinese Medicine Systems Pharmacology (TCMSP), Pubmed,integrative pharmacology-based research platform of traditional Chinese medicine (TCMIP), and Bioin-formatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) wereused to identify the constituents and putative targets of FFEJJ.GeneCards and Dis-GeNET databases were used to identify AA-associated targets. We constructed a herb-component-target network and analyzed the protein-protein interaction (PPI) network. Potential mechanisms were determined using Kyoto Encyclopedia of Genes and Gen-omes (KEGG) pathway enrichment analyses. In addition, an AA model was established using acetylphenylhydrazine (APH) and cetylphenylhydrazine (CTX). Ultra-performance liquid chroma-tography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based serum metabolomics was applied to screen po-tential metabolites and the related pathways associated with AA and the potential anti-anemic effects of FFEJJ. Results A total of 30 active components of FFEJJ and 24 targets were related to AA. PPI network analysis showed that VEGFA, AKT1, IL-6, CASP3, and ICAM1 were key nodes overlapping with proteins known to be related to AA. KEGG pathway enrichment analysis revealed that the presumed targets of FFEJJ were mainly associated with pathways linked to the promotion of hema-topoiesis and improvement of the hematopoietic microenviron-ment. A total of 423 metabolite biomarkers were identified between the control and AA models, which are involved in the development of AA. In contrast, FFEJJ reversed the 79 differential metabolites altered by AA. Pathway analysis suggested that the synergistic effects of FFEJJ were mainly enriched in 24 metabolic pathways. Among them, sphingolipid metabolism, glycerophos-pholipid metabolism, and arachidonic acid metabolism were re-lated to promoting hematopoiesis and improving the hematopoi-etic microenvironment, which partially conforms with network pharmacology. The interaction network formed by three key dif-ferential metabolites, including hydroxy-eicosatetraenoic acid (HETE), sphingosine 1-phosphate (S1P), and lysophosphati-dylcholine (lysoPC), and three predicted network targets (VEGFA, CASP3, and ICAM1) may be the potential mechanism underlying the anti-AA action of the multi-component of FFEJJ.Conclusion FFEJJ could be an alternative treatment option for AA. It acts by promoting hematopoiesis and improving the hema-topoietic microenvironment. Network pharmacology-integrated metabolomics makes it possible to analyze TCMs from a systems perspective and at the molecular level.关键词
复方阿胶浆/再生障碍性贫血/网络药理学/代谢组学/脂质代谢/造血微环境/乙酰苯肼/环磷酰胺Key words
Fufang Ejiao Jiang (复方阿胶浆,FFEJJ)/Aplastic anemia/Network pharmacology/Metabolomics/Lipid metabolomics/Hematopoiesis microenvironment/Acetylphenylhydrazine/Cetylphenylhydrazine引用本文复制引用
何丹,张海潮,易子漾,赵荻,张水寒..基于网络药理学和代谢组学的复方阿胶浆抗再生障碍性贫血研究[J].数字中医药（英文）,2021,4(4):328-342,15.基金项目
We thank for the funding support from the Natural Science Foundation of China(No.81673585,No.81874493,No.81573956) （No.81673585,No.81874493,No.81573956）
Program of Survey of Chinese Medicines of China(No.[2017]66),Science Foundation of Hunan Province(No.2019JJ50345,No.2020JJ5325,No.2021168),Key Research and Devel-opment Project of Changsha Science and Techno-logy(No.kq1901067) （No.[2017]66）
Training Program for Excellent Young Innovators of Changsha(No.kq1802017) （No.kq1802017）
Re-search on the Comprehensive Development and Util-ization of Characteristic Traditional Chinese Medi-cine Resources(No.2060302) （No.2060302）
and the Support of Hunan Province Traditional Chinese Medicine Pre-paration and Quality Traceability Engineering and Technology Center,and the 2011 Collaboration and Innovation Center for Digital Chinese Medicine in Hunan. （）
