PDF(Pubmed)
Abstract：
Acute lung injury (ALI) is a clinically severe lung illness with high incidence rate and mortality. Especially, coronavirus disease 2019 (COVID-19) poses a serious threat to world wide governmental fitness. It has distributed to almost from corner to corner of the universe, and the situation in the prevention and control of COVID-19 remains grave. Traditional Chinese medicine plays a vital role in the precaution and therapy of sicknesses. At present, there is a lack of drugs for treating these diseases, so it is necessary to develop drugs for treating COVID-19 related ALI. Fagopyrum dibotrys (D. Don) Hara is an annual plant of the Polygonaceae family and one of the long-history used traditional medicine in China. In recent years, its rhizomes (medicinal parts) have attracted the attention of scholars at home and abroad due to their significant anti-inflammatory, antibacterial and anticancer activities. It can work on SARS-COV-2 with numerous components, targets, and pathways, and has a certain effect on coronavirus disease 2019 (COVID-19) related acute lung injury (ALI). However, there are few systematic studies on its aerial parts (including stems and leaves) and its potential therapeutic mechanism has not been studied. The phytochemical constituents of rhizome of F. dibotrys were collected using TCMSP database. And metabolites of F. dibotrys\' s aerial parts were detected by metabonomics. The phytochemical targets of F. dibotrys were predicted by the PharmMapper website tool. COVID-19 and ALI-related genes were retrieved from GeneCards. Cross targets and active phytochemicals of COVID-19 and ALI related genes in F. dibotrys were enriched by gene ontology (GO) and KEGG by metscape bioinformatics tools. The interplay network entre active phytochemicals and anti COVID-19 and ALI targets was established and broke down using Cytoscape software. Discovery Studio (version 2019) was used to perform molecular docking of crux active plant chemicals with anti COVID-19 and ALI targets. We identified 1136 chemicals from the aerial parts of F. dibotrys, among which 47 were active flavonoids and phenolic chemicals. A total of 61 chemicals were searched from the rhizome of F. dibotrys, and 15 of them were active chemicals. So there are 6 commonly key active chemicals at the aerial parts and the rhizome of F. dibotrys, 89 these phytochemicals\'s potential targets, and 211 COVID-19 and ALI related genes. GO enrichment bespoken that F. dibotrys might be involved in influencing gene targets contained numerous biological processes, for instance, negative regulation of megakaryocyte differentiation, regulation of DNA metabolic process, which could be put down to its anti COVID-19 associated ALI effects. KEGG pathway indicated that viral carcinogenesis, spliceosome, salmonella infection, coronavirus disease - COVID-19, legionellosis and human immunodeficiency virus 1 infection pathway are the primary pathways obsessed in the anti COVID-19 associated ALI effects of F. dibotrys. Molecular docking confirmed that the 6 critical active phytochemicals of F. dibotrys, such as luteolin, (+) -epicatechin, quercetin, isorhamnetin, (+) -catechin, and (-) -catechin gallate, can combine with kernel therapeutic targets NEDD8, SRPK1, DCUN1D1, and PARP1. In vitro activity experiments showed that the total antioxidant capacity of the aerial parts and rhizomes of F. dibotrys increased with the increase of concentration in a certain range. In addition, as a whole, the antioxidant capacity of the aerial part of F. dibotrys was stronger than that of the rhizome. Our research afford cues for farther exploration of the anti COVID-19 associated ALI chemical compositions and mechanisms of F. dibotrys and afford scientific foundation for progressing modern anti COVID-19 associated ALI drugs based on phytochemicals in F. dibotrys. We also fully developed the medicinal value of F. dibotrys\' s aerial parts, which can effectively avoid the waste of resources. Meanwhile, our work provides a new strategy for integrating metabonomics, network pharmacology, and molecular docking techniques which was an efficient way for recognizing effective constituents and mechanisms valid to the pharmacologic actions of traditional Chinese medicine.
摘要：
急性肺损伤（ALI）是临床上严重的肺部疾病，发病率和死亡率都很高。尤其是,2019年冠状病毒病(COVID-19)对全球政府健康构成严重威胁。它几乎分布在宇宙的各个角落，COVID-19防控形势依然严峻。中医药在疾病的预防和治疗中起着至关重要的作用。目前,缺乏治疗这些疾病的药物，因此有必要开发治疗COVID-19相关ALI的药物。苦参(D.Don）Hara是of科的一年生植物，也是中国历史悠久的传统医学之一。近年来,其根茎(药用部位)因其显著的抗炎作用而受到国内外学者的关注,抗菌和抗癌活性。它可以在SARS-COV-2上使用多种成分，目标,和路径，并对冠状病毒病2019（COVID-19）相关急性肺损伤（ALI）有一定影响。然而,对其地上部分（包括茎和叶）的系统研究很少，其潜在的治疗机制尚未研究。使用TCMSP数据库收集了F.dibotrys根茎的植物化学成分。并通过代谢组学检测了F.dibotrys的地上部分的代谢产物。通过PharmMapper网站工具预测了F.dibotrys的植物化学目标。从GeneCards中检索到COVID-19和ALI相关基因。通过metscape生物信息学工具，通过基因本体论（GO）和KEGG富集了F.dibotrys中COVID-19和ALI相关基因的交叉靶标和活性植物化学物质。使用Cytoscape软件建立并分解了相互作用的网络进入活性植物化学物质和抗COVID-19和ALI靶标。DiscoveryStudio（2019版）用于对具有抗COVID-19和ALI靶标的关键活性植物化学物质进行分子对接。我们从F.dibotrys的地上部分鉴定出1136种化学物质，其中活性类黄酮和酚类化学物质47种。从F.dibotrys的根茎中搜索到了总共61种化学物质，其中15种是活性化学物质。因此，在F.dibotrys的地上部分和根茎上有6种常见的关键活性化学物质，89这些植物化学物质的潜在目标，和211个COVID-19和ALI相关基因。GO富集表明F.dibotrys可能参与影响包含许多生物学过程的基因靶标，例如,巨核细胞分化的负调控，调节DNA代谢过程，这可以归结为其抗COVID-19相关的ALI效应。KEGG通路表明病毒致癌作用，剪接体,沙门氏菌感染,冠状病毒病-COVID-19，军团菌病和人类免疫缺陷病毒1感染途径是困扰F.dibotrys抗COVID-19相关ALI作用的主要途径。分子对接证实了F.dibotrys的6种关键活性植物化学物质，如木犀草素，(+)-表儿茶素,槲皮素,异鼠李素,(+)-儿茶素,和（-）-儿茶素没食子酸酯，可以与内核治疗靶点NEDD8、SRPK1、DCUN1D1和PARP1结合。体外活性实验表明，在一定范围内，随着浓度的增加，二博特草生部分和根茎的总抗氧化能力增加。此外,作为一个整体,黄曲霉地上部分的抗氧化能力强于根茎。我们的研究为进一步探索F.dibotrys的抗COVID-19相关ALI化学成分和机制提供了线索，并为开发基于F.dibotrys植物化学物质的现代抗COVID-19相关ALI药物提供了科学依据。我们还充分开发了F.dibotrys的地上部分的药用价值，能有效避免资源的浪费。同时,我们的工作为整合代谢组学提供了新的策略，网络药理学，和分子对接技术是识别对中药药理作用有效的有效成分和机制的有效途径。
