Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2020

01-12-2020 | Pneumonia | Research article

Network pharmacology to dissect the mechanisms of Yinlai Decoction for pneumonia

Authors: Jingnan Xu, Chen Bai, Ling Huang, Tiegang Liu, Yuxiang Wan, Zian Zheng, Xueyan Ma, Fei Gao, He Yu, Xiaohong Gu

Published in: BMC Complementary Medicine and Therapies | Issue 1/2020

Login to get access

Abstract

Background

Pneumonia is a common respiratory disorder, which brings an enormous financial burden to the medical system. However, the current treatment options for pneumonia are limited because of drug resistance and side effects. Our previous study preliminarily confirmed that Yinlai Decoction (YD), a common prescription for pneumonia in clinical practice, can regulate the expression of inflammatory factors, but the mechanisms are unknown yet.

Methods

In our work, a method named network pharmacology was applied, which investigated the underlying mechanisms of herbs based on a variety of databases. We obtained bioactive ingredients of YD on TCMSP database and collected potential targets of these ingredients by target fishing. Then the pneumonia-related targets database was built by TTD, Drugbank, HPO, OMIM, and CTD. Based on the matching targets between YD and pneumonia, the PPI network was built by STRING to analyze the interactions among these targets and then input into Cytoscape for further topological analysis. DAVID and KEGG were utilized for GO and pathway enrichment analysis. Then rat model based on LPS stimulated pneumonia was used to verify the possible mechanism of YD in treating pneumonia.

Results

Sixty-eight active ingredients, 103 potential targets and 8 related pathways, which likely exert a number of effects, were identified. Three networks were constructed using Cytoscape, which were herb-component-network, YD-pneumonia target network, and herb-component-YD target-pneumonia network. YD was verified to treat LPS-induced pneumonia by regulating the inflammatory factor IL-6, which was a predicted target.

Conclusion

Network analysis indicated that YD could alleviate the symptoms and signs of pneumonia through regulating host immune inflammatory response, angiogenesis and vascular permeability, the barrier function of the airway epithelial cells, hormone releasing and cell growth, proliferation, and apoptosis.
Appendix
Available only for authorised users
Literature
1.
go back to reference Lanks CW, Musani AI, Hsia DW. Community-acquired pneumonia and hospital-acquired pneumonia. Med Clin North Am. 2019;103(3):487–501.PubMedCrossRef Lanks CW, Musani AI, Hsia DW. Community-acquired pneumonia and hospital-acquired pneumonia. Med Clin North Am. 2019;103(3):487–501.PubMedCrossRef
3.
go back to reference Jin Y, Yang H, Ji W, et al. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses. 2020;12(4):E372.PubMedCrossRef Jin Y, Yang H, Ji W, et al. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses. 2020;12(4):E372.PubMedCrossRef
4.
go back to reference Taussig LM, M. Pediatric respiratory medicine. Second ed; 2008. Taussig LM, M. Pediatric respiratory medicine. Second ed; 2008.
5.
go back to reference Liu TG, et al. Influences of Yinlai Tang on sIgA, TNF-α and IL-10 in intestinal mucosal tissues of mice with dyspepsia combined with influenza virus infection. J Beijing Univ Tradit Chinese Med. 2014;37:86–9. Liu TG, et al. Influences of Yinlai Tang on sIgA, TNF-α and IL-10 in intestinal mucosal tissues of mice with dyspepsia combined with influenza virus infection. J Beijing Univ Tradit Chinese Med. 2014;37:86–9.
6.
go back to reference Gao Y, et al. A network pharmacology approach to decipher the mechanisms of anti-depression of Xiaoyaosan formula. World J Tradit Chinese Med. 2018;4:147–62.CrossRef Gao Y, et al. A network pharmacology approach to decipher the mechanisms of anti-depression of Xiaoyaosan formula. World J Tradit Chinese Med. 2018;4:147–62.CrossRef
7.
go back to reference Gao K, et al. Effects of Qijian mixture on type 2 diabetes assessed by Metabonomics, gut microbiota and network pharmacology. Pharmacol Res. 2018;130:93–109.PubMedCrossRef Gao K, et al. Effects of Qijian mixture on type 2 diabetes assessed by Metabonomics, gut microbiota and network pharmacology. Pharmacol Res. 2018;130:93–109.PubMedCrossRef
8.
go back to reference Xiao S, et al. A visual analysis of network pharmacology research trends. World J Tradit Chinese Med. 2018;4:163–9.CrossRef Xiao S, et al. A visual analysis of network pharmacology research trends. World J Tradit Chinese Med. 2018;4:163–9.CrossRef
9.
go back to reference Zhang SD, et al. Exploring the pathways and targets of Shexiang Baoxin pill for coronary heart disease through a network pharmacology approach. World J Tradit Chinese Med. 2018;4:137–46.CrossRef Zhang SD, et al. Exploring the pathways and targets of Shexiang Baoxin pill for coronary heart disease through a network pharmacology approach. World J Tradit Chinese Med. 2018;4:137–46.CrossRef
11.
go back to reference Xu X, Zhang W, Huang C, Li Y, Yu H, Wang Y, Duan J, Ling Y. A Novel Chemometric Method for the Prediction of Human Oral Bioavailability. Int J Mol Sci. 2012;13:6964–82. Xu X, Zhang W, Huang C, Li Y, Yu H, Wang Y, Duan J, Ling Y. A Novel Chemometric Method for the Prediction of Human Oral Bioavailability. Int J Mol Sci. 2012;13:6964–82.
12.
go back to reference Ano R, Kimura YM, Matsuno R, Ueno T, Akamatsu M. Relationships between structure and high-throughput screening permeability of peptide derivatives and related components with artificial membranes: application to prediction of caco-2 cell permeability. Bioorg Med Chem. 2004;12:257–64.PubMedCrossRef Ano R, Kimura YM, Matsuno R, Ueno T, Akamatsu M. Relationships between structure and high-throughput screening permeability of peptide derivatives and related components with artificial membranes: application to prediction of caco-2 cell permeability. Bioorg Med Chem. 2004;12:257–64.PubMedCrossRef
13.
go back to reference Ritchie TJ, Macdonald SJ. How drug-like are ‘ugly’ drugs: do drug-likeness metrics predict ADME behaviour in humans? Drug Discov Today. 2014;19(4):489–95.PubMedCrossRef Ritchie TJ, Macdonald SJ. How drug-like are ‘ugly’ drugs: do drug-likeness metrics predict ADME behaviour in humans? Drug Discov Today. 2014;19(4):489–95.PubMedCrossRef
14.
go back to reference Gong J, et al. ChemMapper: a versatile web server for exploring pharmacology and chemical structure association based on molecular 3D similarity method. Bioinformatics. 2013;29:1827.PubMedCrossRef Gong J, et al. ChemMapper: a versatile web server for exploring pharmacology and chemical structure association based on molecular 3D similarity method. Bioinformatics. 2013;29:1827.PubMedCrossRef
15.
go back to reference Consortium UP. UniProt: a hub for protein information. Nucleic Acids Res. 2015;43:204–12.CrossRef Consortium UP. UniProt: a hub for protein information. Nucleic Acids Res. 2015;43:204–12.CrossRef
16.
go back to reference Li YH, et al. Therapeutic target database update 2018: enriched resource for facilitating bench-to-clinic research of targeted therapeutics. Nucleic Acids Res. 2017;46:D1121–D1127. Li YH, et al. Therapeutic target database update 2018: enriched resource for facilitating bench-to-clinic research of targeted therapeutics. Nucleic Acids Res. 2017;46:D1121–D1127.
17.
go back to reference Law V, et al. DrugBank 4.0: shedding new light on drug metabolism. Nucleic Acids Res. 2014;42:1091–7.CrossRef Law V, et al. DrugBank 4.0: shedding new light on drug metabolism. Nucleic Acids Res. 2014;42:1091–7.CrossRef
18.
19.
go back to reference Hamosh A, et al. Online Mendelian inheritance in man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res. 2005;33:514–7.CrossRef Hamosh A, et al. Online Mendelian inheritance in man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res. 2005;33:514–7.CrossRef
20.
go back to reference Grondin CJ, Davis AP, Wiegers TC, Wiegers JA, Mattingly CJ. Accessing an expanded exposure science module at the comparative Toxicogenomics database. Environ Health Perspect. 2018;126:014501.PubMedPubMedCentralCrossRef Grondin CJ, Davis AP, Wiegers TC, Wiegers JA, Mattingly CJ. Accessing an expanded exposure science module at the comparative Toxicogenomics database. Environ Health Perspect. 2018;126:014501.PubMedPubMedCentralCrossRef
21.
go back to reference Szklarczyk D, et al. STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43:D447.PubMedCrossRef Szklarczyk D, et al. STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43:D447.PubMedCrossRef
23.
go back to reference Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2008;4:44.CrossRef Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2008;4:44.CrossRef
24.
go back to reference Fatma M, Mohamed S. Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles. Int J Nanomedicine. 2017;12:7405–17.CrossRef Fatma M, Mohamed S. Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles. Int J Nanomedicine. 2017;12:7405–17.CrossRef
25.
go back to reference Lu T, et al. Plasma and urinary tanshinol from Salvia miltiorrhiza (Danshen) can be used as pharmacokinetic markers for cardiotonic pills, a cardiovascular herbal medicine. Drug Metabol Dispos Biol Fate Chem. 2008;36:1578.CrossRef Lu T, et al. Plasma and urinary tanshinol from Salvia miltiorrhiza (Danshen) can be used as pharmacokinetic markers for cardiotonic pills, a cardiovascular herbal medicine. Drug Metabol Dispos Biol Fate Chem. 2008;36:1578.CrossRef
26.
27.
go back to reference Jordán F, Liu WC, Memmott DJ. Topological keystone species: measures of positional importance in food webs. Oikos. 2006;112(3):535–46.CrossRef Jordán F, Liu WC, Memmott DJ. Topological keystone species: measures of positional importance in food webs. Oikos. 2006;112(3):535–46.CrossRef
28.
go back to reference Holme P, Huss M, Jeong H. Subnetwork hierarchies of biochemical pathways. Bioinformatics. 2003;19(4):532–8.PubMedCrossRef Holme P, Huss M, Jeong H. Subnetwork hierarchies of biochemical pathways. Bioinformatics. 2003;19(4):532–8.PubMedCrossRef
29.
go back to reference Ma HW, Zeng AP. The connectivity structure, gian strong component and centrality of metabolic networks. Bioinformatics. 2003;19(11):1423–30.PubMedCrossRef Ma HW, Zeng AP. The connectivity structure, gian strong component and centrality of metabolic networks. Bioinformatics. 2003;19(11):1423–30.PubMedCrossRef
30.
go back to reference Shohaib T, Shafique M, Dhanya N, Divakar MC. Importance of Flavonoides In therapeutics. Hygeia J Drugs Med. 2011;3(1):1–18. Shohaib T, Shafique M, Dhanya N, Divakar MC. Importance of Flavonoides In therapeutics. Hygeia J Drugs Med. 2011;3(1):1–18.
32.
go back to reference Takagi R, et al. Wogonin attenuates ovalbumin antigen-induced Neutrophilic airway inflammation by inhibiting Th17 differentiation. Int J Inflamm. 2014;2014:571508.CrossRef Takagi R, et al. Wogonin attenuates ovalbumin antigen-induced Neutrophilic airway inflammation by inhibiting Th17 differentiation. Int J Inflamm. 2014;2014:571508.CrossRef
33.
go back to reference Wakabayashi I, Yasui K. Wogonin inhibits inducible prostaglandin E 2 production in macrophages. Eur J Pharmacol. 2000;406:477–81.PubMedCrossRef Wakabayashi I, Yasui K. Wogonin inhibits inducible prostaglandin E 2 production in macrophages. Eur J Pharmacol. 2000;406:477–81.PubMedCrossRef
34.
go back to reference García-Mediavilla V, et al. The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang liver cells. Eur J Pharmacol. 2007;557:221–9.PubMedCrossRef García-Mediavilla V, et al. The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang liver cells. Eur J Pharmacol. 2007;557:221–9.PubMedCrossRef
35.
go back to reference Zhong X, Kulis M, Guo R, Pons L, Burks AW. Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells. Respir Res. 2006;7:98.CrossRef Zhong X, Kulis M, Guo R, Pons L, Burks AW. Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells. Respir Res. 2006;7:98.CrossRef
36.
go back to reference Li XM, et al. Study on JNK/AP-1 signaling pathway of airway mucus hypersecretion of severe pneumonia under RSV infection. Eur Rev Med Pharmacol Sci. 2016;20:853.PubMed Li XM, et al. Study on JNK/AP-1 signaling pathway of airway mucus hypersecretion of severe pneumonia under RSV infection. Eur Rev Med Pharmacol Sci. 2016;20:853.PubMed
37.
go back to reference Yang Z, et al. Female resistance to pneumonia identifies lung macrophage nitric oxide synthase-3 as a therapeutic target. Elife. 2014;3. Yang Z, et al. Female resistance to pneumonia identifies lung macrophage nitric oxide synthase-3 as a therapeutic target. Elife. 2014;3.
38.
go back to reference Fukunaga K, Kohli P, Bonnans C, Fredenburgh LE, Levy BD. Cyclooxygenase 2 plays a pivotal role in the resolution of acute lung injury. J Immunol. 2005;174:5033–9.PubMedCrossRef Fukunaga K, Kohli P, Bonnans C, Fredenburgh LE, Levy BD. Cyclooxygenase 2 plays a pivotal role in the resolution of acute lung injury. J Immunol. 2005;174:5033–9.PubMedCrossRef
39.
go back to reference Zhang LN, et al. Protective effects of asiaticoside on septic lung injury in mice. Exp Toxicol Pathol Official J Gesellschaft Für Toxikologische Pathologie. 2011;63:519.CrossRef Zhang LN, et al. Protective effects of asiaticoside on septic lung injury in mice. Exp Toxicol Pathol Official J Gesellschaft Für Toxikologische Pathologie. 2011;63:519.CrossRef
40.
go back to reference Chang C, Lee SO, Yeh S, Chang TM. Androgen receptor (AR) differential roles in hormone-related tumors including prostate, bladder, kidney, lung, breast and liver. Oncogene. 2014;33:3225–34.PubMedCrossRef Chang C, Lee SO, Yeh S, Chang TM. Androgen receptor (AR) differential roles in hormone-related tumors including prostate, bladder, kidney, lung, breast and liver. Oncogene. 2014;33:3225–34.PubMedCrossRef
41.
go back to reference Sun CH, et al. Effect of Acrolein on the protein expression of androgen receptor in male rat lung. Biol Reprod. 2012;87:251.CrossRef Sun CH, et al. Effect of Acrolein on the protein expression of androgen receptor in male rat lung. Biol Reprod. 2012;87:251.CrossRef
43.
go back to reference Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990;249:1431–3.PubMedCrossRef Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990;249:1431–3.PubMedCrossRef
44.
go back to reference Abrahams V, Abrahams M. V.M. the role of the nod-like receptor family in trophoblast innate immune responses. J. Reprod. Immunol. 88, 112-117. J Reprod Immunol. 2011;88:112–7.PubMedCrossRef Abrahams V, Abrahams M. V.M. the role of the nod-like receptor family in trophoblast innate immune responses. J. Reprod. Immunol. 88, 112-117. J Reprod Immunol. 2011;88:112–7.PubMedCrossRef
45.
go back to reference Mangodt TC, et al. The role of Th17 and Treg responses in the pathogenesis of RSV infection. Pediatr Res. 2015;78:483–91.PubMedCrossRef Mangodt TC, et al. The role of Th17 and Treg responses in the pathogenesis of RSV infection. Pediatr Res. 2015;78:483–91.PubMedCrossRef
46.
go back to reference Koff JL, Shao MX, Ueki IF, Nadel JA. Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium. Am J Physiol Lung Cell Mol Physiol. 2008;294:L1068.PubMedCrossRef Koff JL, Shao MX, Ueki IF, Nadel JA. Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium. Am J Physiol Lung Cell Mol Physiol. 2008;294:L1068.PubMedCrossRef
47.
go back to reference Mohammed KA, et al. Bacterial induction of pleural mesothelial monolayer barrier dysfunction. Am J Physiol Lung Cell Mol Physiol. 2001;281:119–25.CrossRef Mohammed KA, et al. Bacterial induction of pleural mesothelial monolayer barrier dysfunction. Am J Physiol Lung Cell Mol Physiol. 2001;281:119–25.CrossRef
48.
go back to reference Van DFM, Coenjaerts F, Kimpen JL, Hoepelman AM, Geelen SP. Streptococcus pneumoniae induces secretion of vascular endothelial growth factor by human neutrophils. Infect Immun. 2000;68:4792–4.CrossRef Van DFM, Coenjaerts F, Kimpen JL, Hoepelman AM, Geelen SP. Streptococcus pneumoniae induces secretion of vascular endothelial growth factor by human neutrophils. Infect Immun. 2000;68:4792–4.CrossRef
49.
go back to reference Kanbay M, Kanbay A, Boyacioglu S. Helicobacter pylori infection as a possible risk factor for respiratory system disease: a review of the literature. Respir Med. 2007;101:203–9.PubMedCrossRef Kanbay M, Kanbay A, Boyacioglu S. Helicobacter pylori infection as a possible risk factor for respiratory system disease: a review of the literature. Respir Med. 2007;101:203–9.PubMedCrossRef
50.
go back to reference Wang D, et al. A new prenylated flavonoid i nduces g0/g1 arrest and apoptosis through p38/jnk mapk pathways in human hepatocellular carcinoma cells. Sci Rep. 2017;7(1):5736.PubMedPubMedCentralCrossRef Wang D, et al. A new prenylated flavonoid i nduces g0/g1 arrest and apoptosis through p38/jnk mapk pathways in human hepatocellular carcinoma cells. Sci Rep. 2017;7(1):5736.PubMedPubMedCentralCrossRef
51.
go back to reference Karin W, Nam V, Dimitris K, Norbert B. Inflammatory and catabolic signalling in intervertebral discs: the roles of NF-κB and MAP kinases. Eur Cells Mater. 2012;23:103. Karin W, Nam V, Dimitris K, Norbert B. Inflammatory and catabolic signalling in intervertebral discs: the roles of NF-κB and MAP kinases. Eur Cells Mater. 2012;23:103.
52.
go back to reference Gibbs JD, et al. Cell cycle arrest by transforming growth factor β1 enhances replication of respiratory syncytial virus in lung epithelial cells. J Virol. 2009;83:12424–31.PubMedPubMedCentralCrossRef Gibbs JD, et al. Cell cycle arrest by transforming growth factor β1 enhances replication of respiratory syncytial virus in lung epithelial cells. J Virol. 2009;83:12424–31.PubMedPubMedCentralCrossRef
Metadata
Title
Network pharmacology to dissect the mechanisms of Yinlai Decoction for pneumonia
Authors
Jingnan Xu
Chen Bai
Ling Huang
Tiegang Liu
Yuxiang Wan
Zian Zheng
Xueyan Ma
Fei Gao
He Yu
Xiaohong Gu
Publication date
01-12-2020
Publisher
BioMed Central
Keyword
Pneumonia
Published in
BMC Complementary Medicine and Therapies / Issue 1/2020
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-020-02954-z

Other articles of this Issue 1/2020

BMC Complementary Medicine and Therapies 1/2020 Go to the issue