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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Combination of Network Pharmacology and In Vitro Experiments on LPSinduced A549 Cells to Explore the Molecular Mechanisms of Huanglian Jiedu Decoction Treating Pneumonia

Author(s): Wei Jiang, Jun Liu, Xuequn Zhao and Wenjie Yang*

Volume 26, Issue 3, 2023

Published on: 29 July, 2022

Page: [559 - 575] Pages: 17

DOI: 10.2174/1386207325666220421110032

Price: $65

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Abstract

Objective: Huanglian Jiedu Decoction (HLJDD) was shown to exert a therapeutic effect on pneumonia for a long time in China. However, its pharmacological mechanism remains to be elucidated.

Methods: The active compounds and target proteins of HLJDD were screened from TCMSP, and the pneumonia targets were obtained from GeneCards. GO, and KEGG enrichment was applied in this study. Cytoscape established networks with R-Bioconductor. The affinity between components and targets was detected by molecular docking. Finally, active ingredients and targets were selected to be verified in an inflammatory model established in LPS-induced A549 cells. CCK8 proliferation assay and western blot were performed to test the relative indicators.

Results: 102 bioactive components and 205 targets from 4 herbs in HLJDD were collected. 68 potential therapeutic targets and 55 corresponding compounds were screened to establish the networks. 4 active compounds (quercetin, wogonin, kaempferol and baicalein) and 5 hub genes (IL6, AKT1, CXCL8, CCL2 and IL1B) were then selected to make molecular docking. The results indicated that quercetin and wogonin had a better affinity with CXCL8, CCL2 or IL1B. In vitro experiments revealed that quercetin and wogonin could decrease the proliferation inhibiting and apoptosis of A549 cells injured by LPS. CXCL8, CCL2 or IL1B were downregulated after quercetin or wogonin treatment, compared with LPS-induced A549 cells (P < 0.01).

Conclusion: The current study suggested that the mechanism of HLJDD treating pneumonia might inhibit apoptosis by targeting inflammatory factors, mainly quercetin and wogonin.

Keywords: HuanglianJiedu Decoction, pneumonia, network pharmacology, molecular docking, A549 cells, inflammation response

[1]
Gereige, R.S.; Laufer, P.M. Pneumonia. Pediatr. Rev., 2013, 34(10), 438-456.
[http://dx.doi.org/10.1542/pir.34.10.438] [PMID: 24085792]
[2]
Chuchalin, A.G. Pneumonia: The urgent problem of 21st century medicine. Ter. Arkh., 2016, 88(3), 4-12.
[http://dx.doi.org/10.17116/terarkh20168834-12] [PMID: 27191017]
[3]
Meyer Sauteur, P.M. Challenges and progress toward determining pneumonia etiology. Clin. Infect. Dis., 2020, 71(3), 514-516.
[http://dx.doi.org/10.1093/cid/ciz879] [PMID: 31504351]
[4]
Cilloniz, C.; Martin-Loeches, I.; Garcia-Vidal, C.; San Jose, A.; Torres, A. Microbial etiology of pneumonia: epidemiology, diagnosis and resistance patterns. Int. J. Mol. Sci., 2016, 17(12), E2120.
[http://dx.doi.org/10.3390/ijms17122120] [PMID: 27999274]
[5]
Grief, S.N.; Loza, J.K. Guidelines for the evaluation and treatment of Pneumonia. Prim. Care, 2018, 45(3), 485-503.
[http://dx.doi.org/10.1016/j.pop.2018.04.001] [PMID: 30115336]
[6]
Ho, J.; Ip, M. Antibiotic-resistant community-acquired bacterial pneumonia. Infect. Dis. Clin. North Am., 2019, 33(4), 1087-1103.
[http://dx.doi.org/10.1016/j.idc.2019.07.002] [PMID: 31668192]
[7]
Chen, G.; Xu, Y.; Jing, J.; Mackie, B.; Zheng, X.; Zhang, X.; Wang, J.; Li, X. The anti-sepsis activity of the components of huanglian jiedu decoction with high lipid a-binding affinity. Int. Immunopharmacol., 2017, 46, 87-96.
[http://dx.doi.org/10.1016/j.intimp.2017.02.025] [PMID: 28278436]
[8]
Xu, Y.; Chen, S.; Zhang, L.; Chen, G.; Chen, J. The anti-inflammatory and anti-pruritus mechanisms of huanglian jiedu decoction in the treatment of atopic dermatitis. Front. Pharmacol., 2021, 12, 735295.
[http://dx.doi.org/10.3389/fphar.2021.735295] [PMID: 34925005]
[9]
Zhou, J.; Gu, X.; Fan, X.; Zhou, Y.; Wang, H.; Si, N.; Yang, J.; Bian, B.; Zhao, H. Anti-inflammatory and regulatory effects of huanglian jiedu decoction on lipid homeostasis and the TLR4/MyD88 signaling pathway in lps-induced zebrafish. Front. Physiol., 2019, 10, 1241.
[http://dx.doi.org/10.3389/fphys.2019.01241] [PMID: 31616320]
[10]
Li, X.; Tang, H.; Tang, Q.; Chen, W. Decoding the mechanism of huanglian jiedu decoction in treating pneumonia based on network phar-macology and molecular docking. Front. Cell Dev. Biol., 2021, 9, 638366.
[http://dx.doi.org/10.3389/fcell.2021.638366] [PMID: 33681222]
[11]
Huang, J.; Guo, W.; Cheung, F.; Tan, H-Y.; Wang, N.; Feng, Y. Integrating network pharmacology and experimental models to investigate the efficacy of coptidis and scutellaria containing huanglian jiedu decoction on hepatocellular carcinoma. Am. J. Chin. Med., 2020, 48(1), 161-182.
[http://dx.doi.org/10.1142/S0192415X20500093] [PMID: 31964157]
[12]
Chen, G.; Lu, F.E.; Jin, D.; Xu, L.J.; Wang, K.F. Effect of huanglian jiedu decoction) on glucose transporter 4 expression in adipose and skeletal muscle tissues of insulin resistant rats. Chin. J. Integr. Med., 2007, 13(1), 41-45.
[http://dx.doi.org/10.1007/s11655-007-0041-9] [PMID: 17578317]
[13]
Jin, J.; Zhang, Y.; Hu, W.X.; Zhang, Z.Y.; Xu, N.N.; Zhou, Q.L. Effects of huanglian jiedu decoction on blood lipid metabolism and its related gene expressions in rats with hyperlipidemia. J. Chin. Integr. Med., 2010, 8(3), 275-279.
[http://dx.doi.org/10.3736/jcim20100313] [PMID: 20226151]
[14]
Ren, X.; Shao, X-X.; Li, X-X.; Jia, X-H.; Song, T.; Zhou, W-Y.; Wang, P.; Li, Y.; Wang, X.L.; Cui, Q.H.; Qiu, P.J.; Zhao, Y.G.; Li, X.B.; Zhang, F.C.; Li, Z.Y.; Zhong, Y.; Wang, Z.G.; Fu, X.J. Identifying potential treatments of COVID-19 from traditional chinese medicine (TCM) by using a data-driven approach. J. Ethnopharmacol., 2020, 258, 112932.
[http://dx.doi.org/10.1016/j.jep.2020.112932] [PMID: 32376368]
[15]
Kibble, M.; Saarinen, N.; Tang, J.; Wennerberg, K.; Mäkelä, S.; Aittokallio, T. Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products. Nat. Prod. Rep., 2015, 32(8), 1249-1266.
[http://dx.doi.org/10.1039/C5NP00005J] [PMID: 26030402]
[16]
Luo, T.T.; Lu, Y.; Yan, S.K.; Xiao, X.; Rong, X.L.; Guo, J. Network pharmacology in research of chinese medicine formula: methodology, application and prospective. Chin. J. Integr. Med., 2020, 26(1), 72-80.
[http://dx.doi.org/10.1007/s11655-019-3064-0] [PMID: 30941682]
[17]
Li, S.; Zhang, B. Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin. J. Nat. Med., 2013, 11(2), 110-120.
[http://dx.doi.org/10.1016/S1875-5364(13)60037-0] [PMID: 23787177]
[18]
Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. TCMSP: A data-base of systems pharmacology for drug discovery from herbal medicines. J. Cheminform., 2014, 6(1), 13.
[http://dx.doi.org/10.1186/1758-2946-6-13] [PMID: 24735618]
[19]
Safran, M.; Dalah, I.; Alexander, J.; Rosen, N.; Iny Stein, T.; Shmoish, M.; Nativ, N.; Bahir, I.; Doniger, T.; Krug, H.; Sirota-Madi, A.; Olender, T.; Golan, Y.; Stelzer, G.; Harel, A.; Lancet, D. GeneCards version 3: The human gene integrator. Database (Oxford), 2010, 2010(0), baq020.
[http://dx.doi.org/10.1093/database/baq020] [PMID: 20689021]
[20]
Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res., 2021, 49(D1), D605-D612.
[http://dx.doi.org/10.1093/nar/gkaa1074] [PMID: 33237311]
[21]
Trott, O.; Olson, A.J. AutoDock vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[PMID: 19499576]
[22]
Zhou, X-Y.; Ye, X-G.; He, L-T.; Zhang, S-R.; Wang, R-L.; Zhou, J.; He, Z.S. In vitro characterization and inhibition of the interaction be-tween ciprofloxacin and berberine against multidrug-resistant Klebsiella pneumoniae. J. Antibiot. (Tokyo), 2016, 69(10), 741-746.
[http://dx.doi.org/10.1038/ja.2016.15] [PMID: 26932407]
[23]
Qinghe, G.; Guangyu, L.; Xiaobin, L.; Qingsong, H. Baicalein exerts a protective role in pneumonia caused by Streptococcus pneumoniae. Front. Biosci., 2019, 24(5), 849-858.
[http://dx.doi.org/10.2741/4755] [PMID: 30844717]
[24]
Huang, Y-F.; Bai, C.; He, F.; Xie, Y.; Zhou, H. Review on the potential action mechanisms of Chinese medicines in treating Coronavirus Disease 2019 (COVID-19). Pharmacol. Res., 2020, 158, 104939.
[http://dx.doi.org/10.1016/j.phrs.2020.104939] [PMID: 32445956]
[25]
Takashima, K.; Matsushima, M.; Hashimoto, K.; Nose, H.; Sato, M.; Hashimoto, N.; Hasegawa, Y.; Kawabe, T. Protective effects of in-tratracheally administered quercetin on lipopolysaccharide-induced acute lung injury. Respir. Res., 2014, 15(1), 150.
[http://dx.doi.org/10.1186/s12931-014-0150-x] [PMID: 25413579]
[26]
Wang, C.; Qu, Z.; Kong, L.; Xu, L.; Zhang, M.; Liu, J.; Yang, Z. Quercetin ameliorates lipopolysaccharide-caused inflammatory damage via down-regulation of miR-221 in WI-38 cells. Exp. Mol. Pathol., 2019, 108, 1-8.
[http://dx.doi.org/10.1016/j.yexmp.2019.03.002] [PMID: 30849307]
[27]
Derosa, G.; Maffioli, P.; D’Angelo, A.; Di Pierro, F. A role for quercetin in coronavirus disease 2019 (COVID-19). Phytother. Res., 2021, 35(3), 1230-1236.
[http://dx.doi.org/10.1002/ptr.6887] [PMID: 33034398]
[28]
Tao, Q.; Du, J.; Li, X.; Zeng, J.; Tan, B.; Xu, J.; Lin, W.; Chen, X.L. Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huashi Baidu formula in the treatment of COVID-19. Drug Dev. Ind. Pharm., 2020, 46(8), 1345-1353.
[http://dx.doi.org/10.1080/03639045.2020.1788070] [PMID: 32643448]
[29]
Williamson, G.; Kerimi, A. Testing of natural products in clinical trials targeting the SARS-CoV-2 (Covid-19) viral spike proteinangiotensin converting enzyme-2 (ACE2) interaction. Biochem. Pharmacol., 2020, 178, 114123.
[http://dx.doi.org/10.1016/j.bcp.2020.114123] [PMID: 32593613]
[30]
Tronina, T.; Mrozowska, M.; Bartmańska, A.; Popłoński, J.; Sordon, S.; Huszcza, E. Simple and rapid method for wogonin preparation and its biotransformation. Int. J. Mol. Sci., 2021, 22(16), 8973.
[http://dx.doi.org/10.3390/ijms22168973] [PMID: 34445678]
[31]
Liao, H.; Ye, J.; Gao, L.; Liu, Y. The main bioactive compounds of Scutellaria baicalensis Georgi. for alleviation of inflammatory cytokines: A comprehensive review. Biomed. Pharmacother., 2021, 133, 110917.
[http://dx.doi.org/10.1016/j.biopha.2020.110917] [PMID: 33217688]
[32]
Yao, J.; Pan, D.; Zhao, Y.; Zhao, L.; Sun, J.; Wang, Y.; You, Q.D.; Xi, T.; Guo, Q.L.; Lu, N. Wogonin prevents lipopolysaccharide-induced acute lung injury and inflammation in mice via peroxisome proliferator-activated receptor gamma-mediated attenuation of the nu-clear factor-kappaB pathway. Immunology, 2014, 143(2), 241-257.
[http://dx.doi.org/10.1111/imm.12305] [PMID: 24766487]
[33]
Dukhinova, M.; Kokinos, E.; Kuchur, P.; Komissarov, A.; Shtro, A. Macrophage-derived cytokines in pneumonia: Linking cellular immu-nology and genetics. Cytokine Growth Factor Rev., 2021, 59, 46-61.
[http://dx.doi.org/10.1016/j.cytogfr.2020.11.003] [PMID: 33342718]
[34]
Russo, R.C.; Garcia, C.C.; Teixeira, M.M.; Amaral, F.A. The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases. Expert Rev. Clin. Immunol., 2014, 10(5), 593-619.
[http://dx.doi.org/10.1586/1744666X.2014.894886] [PMID: 24678812]
[35]
Chen, Z.; Shao, X.; Dou, X.; Zhang, X.; Wang, Y.; Zhu, C.; Hao, C.; Fan, M.; Ji, W.; Yan, Y. Role of the mycoplasma pneumoni-ae/interleukin-8/neutrophil axis in the pathogenesis of pneumonia. PLoS One, 2016, 11(1), e0146377.
[http://dx.doi.org/10.1371/journal.pone.0146377] [PMID: 26752656]
[36]
Gibellini, L.; De Biasi, S.; Paolini, A.; Borella, R.; Boraldi, F.; Mattioli, M.; Lo Tartaro, D.; Fidanza, L.; Caro-Maldonado, A.; Meschiari, M.; Iadisernia, V.; Bacca, E.; Riva, G.; Cicchetti, L.; Quaglino, D.; Guaraldi, G.; Busani, S.; Girardis, M.; Mussini, C.; Cossarizza, A. Altered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID-19 pneumonia. EMBO Mol. Med., 2020, 12(12), e13001.
[http://dx.doi.org/10.15252/emmm.202013001] [PMID: 33078545]
[37]
Henrot, P.; Prevel, R.; Berger, P.; Dupin, I. Chemokines in COPD: From implication to therapeutic use. Int. J. Mol. Sci., 2019, 20(11), E2785.
[http://dx.doi.org/10.3390/ijms20112785] [PMID: 31174392]
[38]
Roblek, M.; Protsyuk, D.; Becker, P.F.; Stefanescu, C.; Gorzelanny, C.; Glaus Garzon, J.F.; Knopfova, L.; Heikenwalder, M.; Luckow, B.; Schneider, S.W.; Borsig, L. CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis. Mol. Cancer Res., 2019, 17(3), 783-793.
[http://dx.doi.org/10.1158/1541-7786.MCR-18-0530] [PMID: 30552233]
[39]
Wang, Y.; Zhang, X.; Yang, L.; Xue, J.; Hu, G. Blockade of CCL2 enhances immunotherapeutic effect of anti-PD1 in lung cancer. J. Bone Oncol., 2018, 11, 27-32.
[http://dx.doi.org/10.1016/j.jbo.2018.01.002] [PMID: 29892522]
[40]
Ding, Q.; Liu, G-Q.; Zeng, Y-Y.; Zhu, J-J.; Liu, Z-Y.; Zhang, X.; Huang, J.A. Role of IL-17 in LPS-induced acute lung injury: an in vivo study. Oncotarget, 2017, 8(55), 93704-93711.
[http://dx.doi.org/10.18632/oncotarget.21474] [PMID: 29212183]
[41]
Zhang, L.; Wang, Y.; Shen, H.; Zhao, M. Combined signaling of NF-kappaB and IL-17 contributes to Mesenchymal stem cellsmediated protection for Paraquat-induced acute lung injury. BMC Pulm. Med., 2020, 20(1), 195.
[http://dx.doi.org/10.1186/s12890-020-01232-5] [PMID: 32680482]

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