基于数据挖掘及网络药理学探讨中医药抗呼吸道合胞病毒的用药规律及作用机制

doi:10.3976/j.issn.1002-4026.2023.03.001

Abstract

Abstract:

The study aims to analyze the anti-respiratory syncytial virus (RSV) dosing pattern of traditional Chinese medicine (TCM) using data mining and network pharmacology, and to explore the possible mechanisms of core TCM. The CNKI database was searched to retrieve TCM prescriptions for treating RSV studies. SPSS Statistics 26.0 was used to classify and explore the qualified TCMs on their frequency, nature, taste, four qi and five flavors and their efficacy. Systematic cluster analysis was performed on the TCMs with a frequency greater than five. The compounds and targets were screened using the traditional Chinese medicine systematic pharmacology analysis platform. The above targets were then matched with the RSV disease targets obtained from GeneCards/OMIM database to obtain the key targets of high frequency anti-RSV TCM. Protein-protein interaction network analysis of the key targets was performed using the STRING platform, DAVID database, and the Kyoto encyclopedia of genes and genomes enrichment analysis. Finally, the Chinese herbal medicine-active ingredient-key target-pathway network was constructed using Cytoscape 3.7.1 software and topology analysis was performed. Ninety-one TCM compound prescriptions were identified which involves 121 TCMs that met the criteria. Among them, heat-clearing drugs, phlegm-relieving, cough-suppressing, and asthma-suppressing drugs were mostly found, with the majority attributed to the lung and liver meridians, mainly cold, warm, flat, bitter, pungent, and sweet. Ephedrae Herba, Scutellariae Radix, licorice, and Amygdalus Communis Vas had the highest cumulative frequency and were clustered into one category. A total of 126 active ingredients of Ephedra Herba, Scutellariae Radix, Glycyrrhizae Radix Et Rhizoma, and Armeniacae Semen Amarum were obtained. A total of 110 anti-RSV key targets were obtained, the core targets include GSR, TP53, SOD1, etc., cancer pathway, fluid shear and atherosclerosis pathway, AGE-RAGE signaling pathway, blood lipids and atherosclerotic lipids, etc.

Key words: traditional Chinese medicine compounding, respiratory syncytial virus, dosing pattern, mechanism of action, data mining, network pharmacology

CLC Number:

R285

SUN Tiefeng, DONG Limin, JIAO Ziqi, WANG Ping. Exploration of the dosing pattern and anti-respiratory syncytial virus mechanism of traditional Chinese medicine based on data mining and network pharmacology[J].Shandong Science, 2023, 36(3): 1-9.

Figures/Tables 7

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References 28

[1]	LI Y, WANG X, BLAU D M, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: A systematic analysis[J]. The Lancet, 2022, 399(10340): 2047-2064. DOI: 10.1016/S0140-6736(22)00478-0. doi: 10.1016/S0140-6736(22)00478-0
[2]	崔振泽, 黄燕, 刘明涛, 等. 定喘汤对呼吸道合胞病毒感染大鼠肺组织TSLP、GATA3表达的影响[J]. 中华中医药杂志, 2018, 33(12): 5581-5583.
[3]	谢志鸿, 秦铁林. 双黄连雾化吸入治疗呼吸道合胞病毒所致急性下呼吸道感染[J]. 内蒙古中医药, 2017, 36(1): 54. DOI: 10.16040/j.cnki.cn15-1101.2017.01.054. doi: 10.16040/j.cnki.cn15-1101.2017.01.054
[4]	邹亚, 郭盛, 景晓平, 等. 清肺口服液通过ERK1/2通路调控RSV所致呼吸道炎症损伤的机制[J]. 中国实验方剂学杂志, 2018, 24(2): 86-91. DOI: 10.13422/j.cnki.syfjx.2018020086. doi: 10.13422/j.cnki.syfjx.2018020086
[5]	国家药典委员会. 中华人民共和国药典2020年版一部[M]. 北京: 中国医药科技出版社, 2020.
[6]	RU J L, LI P, WANG J N, et al. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines[J]. Journal of Cheminformatics, 2014, 6: 13. DOI: 10.1186/1758-2946-6-13. doi: 10.1186/1758-2946-6-13 pmid: 24735618
[7]	SHANG Z F, TAN S G, MA D L. Respiratory syncytial virus: From pathogenesis to potential therapeutic strategies[J]. International Journal of Biological Sciences, 2021, 17(14): 4073-4091. DOI: 10.7150/ijbs.64762. doi: 10.7150/ijbs.64762 pmid: 34671221
[8]	世界中医药学会联合会. 网络药理学评价方法指南[J]. 世界中医药, 2021, 16(4): 527-532. DOI: 10.3969/j.issn.1673-7202.2021.04.001. doi: 10.3969/j.issn.1673-7202.2021.04.001
[9]	田景振, 杨振宁. 中医药抗病毒研究思路、理论创新与基本路径[J]. 山东中医杂志, 2018, 37(6): 439-444. DOI: 10.16295/j.cnki.0257-358x.2018.06.001. doi: 10.16295/j.cnki.0257-358x.2018.06.001
[10]	TEIXEIRA T S P, CARUSO Í P, LOPES B R P, et al. Biophysical characterization of the interaction between M2-1 protein ofhRSV and quercetin[J]. International Journal of Biological Macromolecules, 2017, 95: 63-71. DOI: 10.1016/j.ijbiomac.2016.11.033. doi: 10.1016/j.ijbiomac.2016.11.033
[11]	YANG Z F, BAI L P, HUANG W B, et al. Comparison of in vitro antiviral activity of tea polyphenols against influenza A and B viruses and structure-activity relationship analysis[J]. Fitoterapia, 2014, 93: 47-53. DOI: 10.1016/j.fitote.2013.12.011. doi: 10.1016/j.fitote.2013.12.011
[12]	MA S C, DU J, BUT P P H, et al. Antiviral Chinese medicinal herbs against respiratory syncytial virus[J]. Journal of Ethnopharmacology, 2002, 79(2): 205-211. DOI: 10.1016/S0378-8741(01)00389-0. doi: 10.1016/S0378-8741(01)00389-0
[13]	LIU X M, NGUYEN T H, SOKULSKY L, et al. IL-17A is a common and critical driver of impaired lung function and immunopathology induced by influenza virus, rhinovirus and respiratory syncytial virus[J]. Respirology (Carlton, Vic), 2021, 26(11): 1049-1059. DOI: 10.1111/resp.14141. doi: 10.1111/resp.14141
[14]	HABIBI M S, THWAITES R S, CHANG M P, et al. Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection[J]. Science, 2020, 370(6513): eaba9301. DOI: 10.1126/science.aba9301. doi: 10.1126/science.aba9301
[15]	RUSSELL M S, CRESKEY M, MURALIDHARAN A, et al. Unveiling integrated functional pathways leading to enhanced respiratory disease associated with inactivated respiratory syncytial viral vaccine[J]. Frontiers in Immunology, 2019, 10: 597. DOI: 10.3389/fimmu.2019.00597. doi: 10.3389/fimmu.2019.00597 pmid: 30984178
[16]	CHRISTIAANSEN A F, SYED M A, TEN EYCK P P, et al. Altered Treg and cytokine responses in RSV-infected infants[J]. Pediatric Research, 2016, 80(5): 702-709. DOI: 10.1038/pr.2016.130. doi: 10.1038/pr.2016.130 pmid: 27486703
[17]	STOPPELENBURG A J, DE ROOCK S, HENNUS M P, et al. Elevated Th17 response in infants undergoing respiratory viral infection[J]. The American Journal of Pathology, 2014, 184(5): 1274-1279. DOI: 10.1016/j.ajpath.2014.01.033. doi: 10.1016/j.ajpath.2014.01.033
[18]	OOKA T, RAITA Y, FUJIOGI M, et al. Proteomics endotyping of infants with severe bronchiolitis and risk of childhood asthma[J]. Allergy, 2022, 77(11): 3350-3361. DOI: 10.1111/all.15390. doi: 10.1111/all.15390 pmid: 35620861
[19]	SANTOS L D, ANTUNES K H, MURARO S P, et al. TNF-mediated alveolar macrophage necroptosis drives disease pathogenesis during respiratory syncytial virus infection[J]. The European Respiratory Journal, 2021, 57(6): 2003764. DOI: 10.1183/13993003.03764-2020. doi: 10.1183/13993003.03764-2020
[20]	REMMERIE B, Van DEN BOER M, Van LOOY T, et al. Integrating duodenal sampling in a human mass balance study to quantify the elimination pathways of JNJ-53718678, a respiratory syncytial virus fusion protein inhibitor[J]. Advances in Therapy, 2020, 37(1): 578-591. DOI: 10.1007/s12325-019-01162-7. doi: 10.1007/s12325-019-01162-7 pmid: 31832988
[21]	ANDERSSON C K, IWASAKI J, COOK J, et al. Impaired airway epithelial cell wound-healing capacity is associated with airwayremodelling following RSV infection in severe preschool wheeze[J]. Allergy, 2020, 75(12): 3195-3207. DOI: 10.1111/all.14466. doi: 10.1111/all.14466
[22]	DU X Z, YANG Y, YANG M, et al. ITGB4 deficiency induces mucus hypersecretion by upregulating MUC5AC in RSV-infected airway epithelial cells[J]. International Journal of Biological Sciences, 2022, 18(1): 349-359. DOI: 10.7150/ijbs.66215. doi: 10.7150/ijbs.66215 pmid: 34975337
[23]	ASENJO A, GONZÁLEZ-ARMAS J C, VILLANUEVA N. Phosphorylation of human respiratory syncytial virus P protein at serine 54 regulates viral uncoating[J]. Virology, 2008, 380(1): 26-33. DOI: 10.1016/j.virol.2008.06.045. doi: 10.1016/j.virol.2008.06.045 pmid: 18706669
[24]	DAS S, RAUNDHAL M, CHEN J, et al. Respiratory syncytial virus infection of newborn CX3CR1-deficient mice induces a pathogenic pulmonary innate immune response[J]. JCI Insight, 2017, 2(17): e94605. DOI: 10.1172/jci.insight.94605. doi: 10.1172/jci.insight.94605
[25]	ANTALIS E, SPATHIS A, KOTTARIDI C, et al. Th17 serum cytokines in relation to laboratory-confirmed respiratory viral infection: A pilot study[J]. Journal of Medical Virology, 2019, 91(6): 963-971. DOI: 10.1002/jmv.25406. doi: 10.1002/jmv.25406 pmid: 30715745
[26]	HOSAKOTE Y M, KOMARAVELLI N, MAUTEMPS N, et al. Antioxidant mimetics modulate oxidative stress and cellular signaling in airway epithelial cells infected with respiratory syncytial virus[J]. American Journal of Physiology Lung Cellular and Molecular Physiology, 2012, 303(11): L991-L1000. DOI: 10.1152/ajplung.00192.2012. doi: 10.1152/ajplung.00192.2012
[27]	WANG M M, LU M, ZHANG C L, et al. Oxidative stress modulates the expression of toll like receptor 3 during respiratory syncytial virus infection in human lung epithelial A549 cells[J]. Molecular Medicine Reports, 2018, 18(2): 1867-1877. DOI: 10.3892/mmr.2018.9089. doi: 10.3892/mmr.2018.9089
[28]	ALBARRACIN L, GARCIA-CASTILLO V, MASUMIZU Y, et al. Efficient selection of new immunobiotic strains with antiviral effects in local and distal mucosal sites by using Porcine intestinal epitheliocytes[J]. Frontiers in Immunology, 2020, 11: 543. DOI: 10.3389/fimmu.2020.00543. doi: 10.3389/fimmu.2020.00543 pmid: 32322251

中药	频次	频率	中药	频次	频率	中药	频次	频率
麻黄	19	15.7%	金银花	10	8.3%	连翘	6	5.0%
黄芩	18	14.9%	桑白皮	9	7.4%	陈皮	5	4.1%
甘草	17	14.1%	板蓝根	7	5.8%	地龙	5	4.1%
苦杏仁	17	14.1%	半夏	7	5.8%	僵蚕	5	4.1%
石膏	11	9.1%	葶苈子	7	5.8%	紫苏子	5	4.1%

编号	化学成分	中文名称	OB/%	DL	度值	来源
MOL000098	quercetin	槲皮素	46.43	0.28	106	麻黄
MOL000422	kaempferol	山柰酚	41.88	0.24	68	麻黄
MOL000358	beta-sitosterol	β-谷甾醇	36.91	0.75	58	黄芩
MOL000173	wogonin	汉黄芩素	30.68	0.23	33	黄芩
MOL000228	(2R)-7-hydroxy-5-methoxy-2-phenylchroman-4-one	山姜素	55.23	0.20	29	黄芩
MOL000552	5,2'-Dihydroxy-6,7,8-trimethoxyflavone	韧黄芩素I	31.71	0.35	24	黄芩
MOL004328	naringenin	柚皮素	59.29	0.21	15	甘草
MOL002823	herbacetin	草质素苷	36.07	0.27	14	麻黄

靶点	英文名	中文名	度值
GSR	glutathione reductase	谷胱甘肽还原酶	62
TP53	cellular tumor antigen p53	肿瘤蛋白P53	60
SOD1	gene expression of catalase	过氧化氢酶	57
EGFR	epidermal growth factor receptor	表皮生长因子受体	55
CYP3A4	cytochrome P450 3A4	细胞色素P450 3A4	53
GSTP1	glutathione S-transferase P1	谷胱甘肽S-转移酶P1	52
TNF	tumor necrosis factor	肿瘤坏死因子	51
IL-1β	interleukin-1 beta	白细胞介素-1β	50
GSK3B	glycogen synthase kinase-3 beta	糖原合酶激酶-3β	50
PTGS2	prostaglandin-endoperoxide synthase 2	前列腺素-内过氧化物合酶2	48

Exploration of the dosing pattern and anti-respiratory syncytial virus mechanism of traditional Chinese medicine based on data mining and network pharmacology

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