热毒宁注射液治疗新型冠状病毒肺炎的有效成分和机制初探

中国医药导刊 ›› 2020, Vol. 22 ›› Issue (3): 145-152.

所属专题： "新冠肺炎防控"专栏

• 新冠肺炎防治专栏 • 下一篇

热毒宁注射液治疗新型冠状病毒肺炎的有效成分和机制初探

高亚1，刘明1，杨珂璐2，施树珍1，刘依嘉3，孙炜3，田金徽1，4*

1. 兰州大学循证医学中心，兰州大学基础医学院，甘肃兰州 730000；
     2. 兰州大学循证护理中心，兰州大学护理学院，甘肃兰州 730000；
     3. 兰州大学第二临床医学院，甘肃兰州 730000；
     4. 兰州大学甘肃省循证医学与临床转化重点实验室，甘肃兰州 730000

收稿日期:2020-04-09 修回日期:2020-04-10 出版日期:2020-03-31 发布日期:2020-05-14
基金资助:
甘肃省循证医学与临床转化重点实验室应急科研专项（项目编号：GSEBMKT-2020YJ01；项目名称：COVID-19防控）

Preliminary Study on the Effective Components and Mechanism of Reduning Injection in the Treatment of Coronavirus Disease 2019

1.Evidence-Based Medicine Center， School of Basic Medical Sciences， Lanzhou University， Gansu Lanzhou 730000， China；
     2.Evidence-Based Nursing Center， School of Nursing， Lanzhou University， Gansu Lanzhou 730000， China；
     3.The Second Clinical Medical College of Lanzhou University， Gansu Lanzhou 730000， China；
     4 Key Laboratory of Evidence-based Medicine and Knowledge Translation of Gansu Province， Lanzhou University，
     Gansu Lanzhou 730000，China

Received:2020-04-09 Revised:2020-04-10 Online:2020-03-31 Published:2020-05-14
Contact: Jinhui HuiTian E-mail:tjh996@163.com
Supported by:
COVID-19防控

摘要/Abstract

摘要： 目的：基于网络药理学探索热毒宁注射液治疗新型冠状病毒肺炎（Corona Virus Disease 2019，COVID-19）的作用机制。方法：从TCMSP数据库获取热毒宁注射液的有效化合物和靶点，从GeneCards和OMIM数据库获取COVID-19相关靶点，构建有效化合物-靶点网络。利用STRING 数据库构建蛋白互作（PPI）网络，使用R软件进行GO富集分析与KEGG通路富集分析，并使用Cytoscape 3.7.2软件构建靶点-信号通路网络图。结果：筛选得到热毒宁注射液50个有效化合物，对应208个靶点，COVID-19相关靶点259个，共同靶点44个。GO富集分析得富集条目1468个，在生物过程中主要富集条目为脂多糖应答、对细菌来源分子的反应和对凋亡信号通路的调节。KEGG富集分析得到信号通路150条，包括AGE-RAGE、Kaposi sarcoma-associated herpesvirus infection、Human cytomegalovirus infection、TNF和IL-17等通路。结论：热毒宁注射液可能通过其有效成分槲皮素、山柰酚、木犀草素、异鼠李碱和金圣草（黄）素等作用于炎性细胞因子、丝裂原活化蛋白激酶等靶点调控AGE-RAGE、Human cytomegalovirus infection、TNF和IL-17等通路发挥治疗COVID-19的作用。

关键词: 热毒宁注射液, 新型冠状病毒肺炎（COVID-19）, 网络药理学, 机制, 信号通路

Abstract: Objective: This study aimed to explore the mechanism of Reduning injection in the treatment of Corona Virus Disease 2019 (COVID-19) based on network pharmacology. Methods: The effective compounds and targets of Reduning Injection were obtained from the TCMSP database, the COVID-19 related targets were obtained from the GeneCards and OMIM databases, and an effective compound-target network was constructed. A PPI network was constructed using the STRING database, GO enrichment analysis and KEGG pathway enrichment analysis were performed using R software, and a target-signal pathway network map was constructed using Cytoscape 3.7.2 software. Results: 50 effective compounds were obtained from Reduning injection, corresponding to 208 targets. 259 COVID-19 related targets were obtained, of which 44 were common targets. GO enrichment analysis yielded 1468 enrichment terms. The main enrichment terms in the biological process were the response to lipopolysaccharide, response to molecule of bacterial origin, and the regulation of apoptotic signaling pathway. KEGG enrichment analysis yielded 150 signal pathways, including AGE-RAGE, Kaposi sarcoma-associated herpesvirus infection, Human cytomegalovirus infection, TNF and IL-17. Conclusion: Reduning injection may act on targets such as inflammatory cytokines and mitogen-activated protein kinases through the active ingredients, including quercetin, kaempferol, luteolin, isorhamnetin, and chryseriol, to regulate pathways such as AGE-RAGE, Human cytomegalovirus infection, TNF and IL-17 to play a role in treating COVID-19.

Key words: Reduning injection, coronavirus disease 2019 (COVID-19), network pharmacology, mechanism, signal pathway

中图分类号:

高亚, 刘明, 杨珂璐, 施树珍, 刘依嘉, 孙炜, 田金徽, . 热毒宁注射液治疗新型冠状病毒肺炎的有效成分和机制初探[J]. 中国医药导刊, 2020, 22(3): 145-152.

GAO Ya, LIU Ming, YANG Kelu, SHI Shuzhen, LIU Yijia, SUN Wei, TIAN Jinhui, . Preliminary Study on the Effective Components and Mechanism of Reduning Injection in the Treatment of Coronavirus Disease 2019[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2020, 22(3): 145-152.

参考文献

[1] Nanshan C, Min Z, Xuan D, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study[J]. Lancaet,2020,395(10223):507-513.
[2] Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia[J]. N Eng J Med,2020,382(13):1199-1207.
[3] Ralph R, Lew J, Zeng T, et al. 2019-nCoV (Wuhan virus), a novel Coronavirus: human-to-human transmission, travel-related cases, and vaccine readiness[J]. J Infect Dev Ctries,2020, 14(1):3-17.
[4] Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China[J]. The Lancet,2020,395(10223):497-506.
[5] Chan J F, Yuan S, Kok K, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster[J]. The Lancet,2020,395(10223):514-523.
[6] 王法财,沈炳香,何春远,等.连花清瘟颗粒对新型冠状病毒肺炎的临床疗效及其机制的网络药理学研究[J].中药药理与临床,2020,doi:10.13412/j.cnki.zyyl.20200318.001.
[7] 王毅,李翔,张俊华,等.基于网络药理学的宣肺败毒汤治疗新型冠状病毒肺炎机制研究[J].中国中药杂志,2020,doi:10.19540/j.cnki.cjcmm.20200325.401.
[8] 党娇娇,吕健,孙梦华,等.热毒宁注射液治疗急性气管-支气管炎的系统评价与Meta分析[J].中国中药杂志,2019,44(24):5294-5302.
[9] 张云燕,徐王彦君,汤响林,等.热毒宁注射液对大鼠肝脏CYP450酶的影响[J].中国中药杂志,2015,40(14):2737-2742.
[10] 刘红菊,陶晓南,辛建宝,等.中药热毒宁对急性肺损伤兔肺内致炎因子的影响[J].中国新药与临床杂志,2007,26(6):446.
[11] 高万朋,王时光,崔壮,等.热毒宁注射液治疗社区获得性肺炎疗效的Meta分析[J].中国中药杂志,2011,36(24):3539.
[12] 国家卫生健康委办公厅,国家中医药管理局办公室.关于印发新型冠状病毒肺炎诊疗方案（试行第七版）的通知[EB/OL].(2020-03-03). http://www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1989.Shtml.
[13] Magder S. Reactive oxygen species: toxic molecules or spark of life[J]. Critical Care,2006,10:208.
[14] Takashima K, Matsushima M, Hashimoto K, et al. Protective effects of intratracheally administered quercetin on lipopolysaccharide-induced acute lung injury[J]. Respiratory Research,2014,15(1):150.
[15] 李聪,胡强,张燕翔.槲皮素的药理学活性研究进展[J].湖北中医杂志,2018,40(6):63-66.
[16] 雷晓青,陈鳌,刘毅,等.山萘酚药理作用的研究进展[J].微量元素与健康研究,2017,34(2):61-62.
[17] 谭蓓蓓,郭婧澜,刘倩,等.山柰酚对前列腺癌骨转移模型小鼠的作用及其机制研究[J].中国临床药理学杂志,2020,36(3):293-296.
[18] Dong X, Fu J, Yin X, et al. Emodin: a review of its pharmacology, toxicity and pharmacokinetics[J]. Phytother Res,2016,30(8):1207-1218.
[19] 李海波,于洋,王振中,等.热毒宁注射液抗病毒活性成分研究(Ⅰ)[J].中草药,2014,45(12):1682-1688.
[20] 许冬玉,许玉龙,王至婉,等.基于网络药理学研究清肺排毒汤治疗新型冠状病毒肺炎的作用机制[J].中药药理与临床,2020,doi:10.13412/j.cnki.zyyl.20200305.001.
[21] Birt DF, Hendrich S, Wang W. Dietary agents in cancer prevention: flavonoids and isoflavonoids[J]. Pharmcol Ther,2001,90(2-3):157-177.
[22] Yang JH, Kim SC, Shin BY, et al. O-Methylated flavonol isorhamnetin prevents acute inflammation through blocking of NF-κB activation[J]. Food Chem Toxicol,2013;59:362-372.
[23] Choi YH. The cytoprotective effect of isorhamnetin against oxidative stress is mediated by the upregulation of the Nrf2-dependent HO-1 expression in C2C12 myoblasts through scavenging reactive oxygen species and ERK inactivation[J]. Gen Physiol Biophys,2016;35:145-154.
[24] Kim SY, Jin CY, Kim CH, et al. Isorhamnetin alleviates lipopolysaccharide-induced inflammatory responses in BV2 microglia by inactivating NF-κB, blocking the TLR4 pathway and reducing ROS generation[J]. Int J Mol Med,2019,43(2):682-692.
[25] 谭会洁,宋俊科,石峰,等.异鼠李素激活PI3K/Akt /GSK-3β/CREB信号通路减轻鱼藤酮诱导的PC12细胞损伤[J].中国药理学通报,2020,36(2):272-276.
[26] Limboonreung T, Tuchinda P, Chongthammakun S. Chrysoeriol mediates mitochondrial protection via PI3K/Akt pathway in MPP+ treated SH-SY5Y cells[J]. Neurosci Lett,2020,714:134545.
[27] 龚普阳,郭瑜婕,李晓朋,等.基于网络药理学与分子对接技术的金花清感颗粒防治新型冠状病毒肺炎的潜在药效物质研究[J].中草药,2020,doi:10.7501/j.issn.0253-2670.2020.07.
[28] 王林,杨志华,张浩然,等.连花清瘟治疗新型冠状病毒（2019?nCoV）肺炎网络药理学研究与初证[J].中药材,2020,43(3):772-778.
[29] 吴昊,王佳琪,杨雨薇,等.基于网络药理学和分子对接技术初步探索“清肺排毒汤”抗新型冠状病毒肺炎作用机制[J].药学学报,2020,55(3):374-383.
[30] 孔艺,吴红卫,陈永,等.基于网络药理学和分子对接探讨痰热清注射液治疗新型冠状病毒肺炎机制[J].中草药,[2020-03-19]. http://kns.cnki.net/kcms/detail/12.1108.R.20200318.1518.002.html.
[31] 余春波,卢明,邵雷,等.relA基因敲除对多黏菌素抗鲍曼不动杆菌异质性耐药的影响[J].上海交通大学学报(医学版),2019,39(9):1004-1010.
[32] Etienne M, Kenn G. Molecular mechanisms underlying bacterial persisters[J]. Cell,2014,157(3):539-548.
[33] 吕瑾,杨胜祥,华晓芳,等.黑芥子苷通过p38/JNK MAPK信号通路对阿霉素心脏毒性的保护作用[J].国际心血管病杂志,2020,47(1):48-51.
[34] 刘天宇,陈艳红,赵权.白细胞介素6在分子生物学和畜禽疾病中的研究进展[J].黑龙江畜牧兽医月刊,2018,(1):90-93.
[35] 贾春翠,饶春明,于雷.以白细胞介素-6信号通路为靶点的生物技术药物研究进展[J].中国生物制品学杂志,2019,32(9):1048-1053.
[36] 胡龙,叶啟发,王彦峰,等.细胞凋亡在脑死亡供体肾中的研究进展[J].生物医学工程与临床, 2014,18(1):90-93.
[37] Li J, Yuan J. Caspases in apoptosis and beyond[J]. Oncogene,2008,27(48):6194-6206.
[38] Kaden-Volynets V, Günther C, Zimmermann J, et al. Deletion of the Casp8 gene in mice results in ileocolitis, gut barrier dysfunction, and malassimilation, which can be partially attenuated by inulin or sodium butyrate[J]. Am J Physiol Gastrointest Liver Physiol,2019,317(4):G493-G507.
[39] Clarke DL, Clifford RL, Jindarat S, et al. TNF-a and IFN-y synergistically enhance transcriptional activation of CXCL10 in human airway smooth muscle cells via STAT-1, NF-KB, and the transcriptional coactivator CREB-binding protein[J]. J Biol Chem,2010,285(38):29101-2910.
[40] Liu FX, Fu YC, Wei CJ, et al. The expression of GPR109A, NF-KB and IL-1β in peripheral blood leukocytes from patients with type 2 diabetes[J]. Ann Clin Lab Sci,2014,44(4):443-448.
[41] Xu Y, Nie L, Yin YG, et al. Resveratrol protects against hyperglycemia-induced oxidative damage to mitochondria by activating SIRT1 in rat mesangial cells[J]. Toxicol Appl Pharmacol,2012,259(3):395-401.
[42] Noack M, Miossec P. Selected cytokine pathways in rheumatoid arthritis[J]. Semin Im munopathol,2017,39(4):365-383.

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热毒宁注射液治疗新型冠状病毒肺炎的有效成分和机制初探

Preliminary Study on the Effective Components and Mechanism of Reduning Injection in the Treatment of Coronavirus Disease 2019

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