Quinoxaline 1, 4-dioxides (QdNOs) are quinox-aline derivatives which have been used as an-timicrobial agents and growth promoters in animals widely. They are also assumed to cure human disease such as anticancer, anti...Quinoxaline 1, 4-dioxides (QdNOs) are quinox-aline derivatives which have been used as an-timicrobial agents and growth promoters in animals widely. They are also assumed to cure human disease such as anticancer, antitubercular and inhibiting parasite. QdNOs such as carbadox and their major metabolites induced a special decline of aldosterone production from the swine adrenal in vivo and in vitro, and thus cause hypovolemia, hyponatremia and hyperkalemia. This can also be expected to be the case for human. As a mainly physiological hormone and a novel steroid with potent mineralocorticoid activity, aldosterone plays an important role in the pathophysiological process of brain, renal and heart disease progression and may be a renal and vascular risk factor. Here, we provide evidence to support the hypothesis that QdNOs may lead potential benefits in aldosterone dysmetabolism disease via the synthesis deficiency of aldosterone in adrenal and/or the cardiovascular tissues. If the hypothesis is true, it may provide a new option into the therapy for aldosterone dysmetabolism disease, especially in cardiovascular system, and thus assume a broader application of QdNOs.展开更多
目的:基于网络药理学及分子对接技术探讨香连片对新型冠状病毒肺炎(Corona Virus Disease 2019, COVID-19)的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Anal...目的:基于网络药理学及分子对接技术探讨香连片对新型冠状病毒肺炎(Corona Virus Disease 2019, COVID-19)的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, TCMSP)、PubChem数据库、生物信息学分析工具(a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine, BATMAN-TCM)及SwissTarget Prediction平台查询香连片活性成分及其对应的靶点基因;根据大于2倍中位数的节点度值(degree)为条件,筛选香连片关键活性成分,并运用Cytoscape 3.6.1软件绘制关键活性成分-对应靶点网络;通过GeneCards及PHARMGKB疾病数据库,以"coronavirus pneumonia"、"COVID-19"及"SARS-CoV-2"为关键词进行检索疾病靶点基因。运用Cytoscape 3.6.1软件进行交集,得到共同靶点并构建成分-靶点-疾病网络图;通过STRING网站对共同靶点构建蛋白相互作用(Protein Protein interaction, PPI)网络,通过DAVID数据库对共同靶点进行基因本位(gene ontology, GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)分析;利用CB-Dock网站对筛选出的活性成分及抗病毒化药和SARS-CoV-2 3CL水解酶及血管紧张素转化酶Ⅱ (angiotensin converting enzyme Ⅱ, ACE2)进行分子对接。结果:香连片共得到41个活性成分,其中16个关键活性成分,并与疾病靶点相交得到24个共同靶点;GO功能富集得到分子功能(molecular function, MF)、细胞组分(cellular component, CC)及其所参与的生物过程(biological process, BP)分别为125条、16条及24条;KEGG富集得到94条通路,其通路多与免疫反应和炎症反应有关,主要有PI3K-Akt、Ras、HIF-1、MAPK、NF-kB以及TNF等信号通路;分子对接得出黄柏酮、氧化小檗碱、吴茱萸碱、吴茱萸次碱及豆甾醇等多种成分与SARS-CoV-2 3CL水解酶及ACE2的对接亲和力均强于2种临床化学药物(阿比多尔及利巴韦林)。结论:香连片多是通过作用于MAPK家族、IL1B、NFKB1、CASP3、CCL5、TNF等靶点因子来调节PI3K-Akt、MAPK、NF-kB及TNF等炎症免疫通路,以多成分、多靶点、多途径参与COVID-19的多种生理过程,从而对COVID-19有一定治疗作用;在中药成分上,黄柏酮、氧化小檗碱、吴茱萸碱、吴茱萸次碱、豆甾醇、吴茱萸酰胺类成分等可以很好作用于COVID-19治疗中涉及到的2种关键酶(SARS-CoV-2 3CL水解酶及ACE2),故这几种中药单体成分有作为治疗COVID-19的新药潜能。展开更多
文摘Quinoxaline 1, 4-dioxides (QdNOs) are quinox-aline derivatives which have been used as an-timicrobial agents and growth promoters in animals widely. They are also assumed to cure human disease such as anticancer, antitubercular and inhibiting parasite. QdNOs such as carbadox and their major metabolites induced a special decline of aldosterone production from the swine adrenal in vivo and in vitro, and thus cause hypovolemia, hyponatremia and hyperkalemia. This can also be expected to be the case for human. As a mainly physiological hormone and a novel steroid with potent mineralocorticoid activity, aldosterone plays an important role in the pathophysiological process of brain, renal and heart disease progression and may be a renal and vascular risk factor. Here, we provide evidence to support the hypothesis that QdNOs may lead potential benefits in aldosterone dysmetabolism disease via the synthesis deficiency of aldosterone in adrenal and/or the cardiovascular tissues. If the hypothesis is true, it may provide a new option into the therapy for aldosterone dysmetabolism disease, especially in cardiovascular system, and thus assume a broader application of QdNOs.
文摘目的:基于网络药理学及分子对接技术探讨香连片对新型冠状病毒肺炎(Corona Virus Disease 2019, COVID-19)的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, TCMSP)、PubChem数据库、生物信息学分析工具(a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine, BATMAN-TCM)及SwissTarget Prediction平台查询香连片活性成分及其对应的靶点基因;根据大于2倍中位数的节点度值(degree)为条件,筛选香连片关键活性成分,并运用Cytoscape 3.6.1软件绘制关键活性成分-对应靶点网络;通过GeneCards及PHARMGKB疾病数据库,以"coronavirus pneumonia"、"COVID-19"及"SARS-CoV-2"为关键词进行检索疾病靶点基因。运用Cytoscape 3.6.1软件进行交集,得到共同靶点并构建成分-靶点-疾病网络图;通过STRING网站对共同靶点构建蛋白相互作用(Protein Protein interaction, PPI)网络,通过DAVID数据库对共同靶点进行基因本位(gene ontology, GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)分析;利用CB-Dock网站对筛选出的活性成分及抗病毒化药和SARS-CoV-2 3CL水解酶及血管紧张素转化酶Ⅱ (angiotensin converting enzyme Ⅱ, ACE2)进行分子对接。结果:香连片共得到41个活性成分,其中16个关键活性成分,并与疾病靶点相交得到24个共同靶点;GO功能富集得到分子功能(molecular function, MF)、细胞组分(cellular component, CC)及其所参与的生物过程(biological process, BP)分别为125条、16条及24条;KEGG富集得到94条通路,其通路多与免疫反应和炎症反应有关,主要有PI3K-Akt、Ras、HIF-1、MAPK、NF-kB以及TNF等信号通路;分子对接得出黄柏酮、氧化小檗碱、吴茱萸碱、吴茱萸次碱及豆甾醇等多种成分与SARS-CoV-2 3CL水解酶及ACE2的对接亲和力均强于2种临床化学药物(阿比多尔及利巴韦林)。结论:香连片多是通过作用于MAPK家族、IL1B、NFKB1、CASP3、CCL5、TNF等靶点因子来调节PI3K-Akt、MAPK、NF-kB及TNF等炎症免疫通路,以多成分、多靶点、多途径参与COVID-19的多种生理过程,从而对COVID-19有一定治疗作用;在中药成分上,黄柏酮、氧化小檗碱、吴茱萸碱、吴茱萸次碱、豆甾醇、吴茱萸酰胺类成分等可以很好作用于COVID-19治疗中涉及到的2种关键酶(SARS-CoV-2 3CL水解酶及ACE2),故这几种中药单体成分有作为治疗COVID-19的新药潜能。
