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Combinatorial Chemistry & High Throughput Screening

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

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Research Article

Therapeutic Mechanism of Xiaoqinglong Decoction against COVID-19 Based on Network Pharmacology and Molecular Docking Technology

Author(s): Hai-Li Li, Jian-Peng Zhou and Jing-Min Deng*

Volume 25, Issue 13, 2022

Published on: 21 April, 2022

Page: [2264 - 2277] Pages: 14

DOI: 10.2174/1386207325666220228154231

Price: $65

Abstract

Background: A xiaoqinglong decoction (XQLD) has been proven effective in treating severe coronavirus disease 2019 (COVID-19) cases; however, the mechanism remains unclear.

Objective: In the current study, we used network pharmacology and molecular docking technology to identify the effective components, potential targets, and biological pathways of XQLD against COVID-19.

Methods: Public databases were searched to determine the putative targets of the active compounds of XQLD and COVID-19-related targets. STRING and Cytoscape were used to establish the protein-protein interaction network and drug component, along with the target-pathway network. The DAVID database was used to enrich the biological functions and signaling pathways. AutoDock Vina was used for virtual docking.

Results: We identified 138 active compounds and 259 putative targets of XQLD. Biological network analysis showed that quercetin, beta-sitosterol, kaempferol, stigmasterol, and luteolin may be critical ingredients of XQLD, whereas VEGFA, IL-6, MAPK3, CASP3, STAT3, MAPK1, MAPK8, CASP8, CCL2, and FOS may be candidate drug targets. Enrichment analysis illustrated that XQLD could function by regulating viral defense, inflammatory response, immune response, and apoptosis. Molecular docking results showed a high affinity between the critical ingredients and host cell target proteins.

Conclusion: This study uncovered the underlying pharmacological mechanism of XQLD against COVID-19. These findings lay a solid foundation for promoting the development of new drugs against severe acute respiratory syndrome coronavirus-2 infection and may contribute to the global fight against the COVID-19 pandemic.

Keywords: COVID-19, xiaoqinglong decoction (XQLD), network pharmacology, molecular docking, Traditional Chinese Medicine (TCM), viral infectious diseases.

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[1]
Wang, C.; Horby, P.W.; Hayden, F.G.; Gao, G.F. A novel coronavirus outbreak of global health concern. Lancet, 2020, 395(10223), 470-473.
[http://dx.doi.org/10.1016/S0140-6736(20)30185-9] [PMID: 31986257]
[2]
Chen, N.; Zhou, M.; Dong, X.; Qu, J.; Gong, F.; Han, Y.; Qiu, Y.; Wang, J.; Liu, Y.; Wei, Y.; Xia, J.; Yu, T.; Zhang, X.; Zhang, L. Epide-miological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 2020, 395(10223), 507-513.
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]
[3]
Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; Cheng, Z.; Yu, T.; Xia, J.; Wei, Y.; Wu, W.; Xie, X.; Yin, W.; Li, H.; Liu, M.; Xiao, Y.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao, B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395(10223), 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[4]
Lim, J.; Jeon, S.; Shin, H.Y.; Kim, M.J.; Seong, Y.M.; Lee, W.J.; Choe, K.W.; Kang, Y.M.; Lee, B.; Park, S.J. Case of the index patient WHO caused tertiary transmission of covid-19 infection in korea: the application of lopinavir/ritonavir for the treatment of COVID-19 in-fected pneumonia monitored by quantitative RT-PCR. J. Korean Med. Sci., 2020, 35(6), e79.
[http://dx.doi.org/10.3346/jkms.2020.35.e79] [PMID: 32056407]
[5]
Wang, D.; Hu, B.; Hu, C.; Zhu, F.; Liu, X.; Zhang, J.; Wang, B.; Xiang, H.; Cheng, Z.; Xiong, Y.; Zhao, Y.; Li, Y.; Wang, X.; Peng, Z. Clini-cal characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA, 2020, 323(11), 1061-1069.
[http://dx.doi.org/10.1001/jama.2020.1585] [PMID: 32031570]
[6]
Ma, Y.; Chen, M.; Guo, Y.; Liu, J.; Chen, W.; Guan, M.; Wang, Y.; Zhao, X.; Wang, X.; Li, H.; Meng, L.; Wen, Y.; Wang, Y. Prevention and treatment of infectious diseases by traditional Chinese medicine: a commentary. APMIS, 2019, 127(5), 372-384.
[http://dx.doi.org/10.1111/apm.12928] [PMID: 31124203]
[7]
Song, P.; Zhao, L.; Li, X.; Su, J.; Jiang, Z.; Song, B.; Liu, W.; Tang, S.; Lei, Y.; Ding, Q.; Yang, Z.; Lin, J.; Wei, Y.; Tong, X. Interpretation of the traditional chinese medicine portion of the diagnosis and treatment protocol for corona virus disease 2019 (Trial Version 7). J. Tradit. Chin. Med., 2020, 40(3), 497-508.
[PMID: 32506865]
[8]
Fang, L.; Karakiulakis, G.; Roth, M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir. Med., 2020, 8(4), e21.
[http://dx.doi.org/10.1016/S2213-2600(20)30116-8] [PMID: 32171062]
[9]
Filippou, P.S.; Karagiannis, G.S. Cytokine storm during chemotherapy: a new companion diagnostic emerges? Oncotarget, 2020, 11(3), 213-215.
[http://dx.doi.org/10.18632/oncotarget.27442] [PMID: 32076483]
[10]
Yanfeng, X.; Yongdui, R.; Xiaoru, L. Clinical observation on 8 novel coronavirus pneumonia cases in dongguan area treated by poge jiux-in decoction and xiaoqinglong decoction. Clin. J. Trad. Chinese Med., 2020, 32(07), 1204-1208.
[11]
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, 13.
[http://dx.doi.org/10.1186/1758-2946-6-13] [PMID: 24735618]
[12]
Szklarczyk, D.; Gable, A.L.; Lyon, D.; Junge, A.; Wyder, S.; Huerta-Cepas, J.; Simonovic, M.; Doncheva, N.T.; Morris, J.H.; Bork, P.; Jensen, L.J.; Mering, C.V. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res., 2019, 47(D1), D607-D613.
[http://dx.doi.org/10.1093/nar/gky1131] [PMID: 30476243]
[13]
WHO. International organizations, vaccine manufacturers take stock of COVID-19 vaccine roll out, share views for 2022. 2021. Available from: https://www.who.int/
[14]
Irfan, N.; Chagla, Z. In South Africa, a 2-dose Oxford/AZ vaccine did not prevent mild to moderate COVID-19 (cases mainly B.1.351 variant). Ann. Intern. Med., 2021, 174(5), JC50.
[http://dx.doi.org/10.7326/ACPJ202105180-050] [PMID: 33939483]
[15]
Wang, J.; Peng, Y.; Xu, H.; Cui, Z.; Williams, R.O., III The COVID-19 vaccine race: Challenges and opportunities in vaccine formulation. AAPS PharmSciTech, 2020, 21(6), 225.
[http://dx.doi.org/10.1208/s12249-020-01744-7] [PMID: 32761294]
[16]
Yin, X.X.; Zheng, X.R.; Peng, W.; Wu, M.L.; Mao, X.Y. Vascular endothelial growth factor (VEGF) as a vital target for brain inflammation during the COVID-19 outbreak. ACS Chem. Neurosci., 2020, 11(12), 1704-1705.
[http://dx.doi.org/10.1021/acschemneuro.0c00294] [PMID: 32485101]
[17]
Fajgenbaum, D.C. Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease. Blood, 2018, 132(22), 2323-2330.
[http://dx.doi.org/10.1182/blood-2018-05-848671] [PMID: 30487129]
[18]
Gubernatorova, E.O.; Gorshkova, E.A.; Polinova, A.I.; Drutskaya, M.S. IL-6: Relevance for immunopathology of SARS-CoV-2. Cytokine Growth Factor Rev., 2020, 53, 13-24.
[http://dx.doi.org/10.1016/j.cytogfr.2020.05.009] [PMID: 32475759]
[19]
Murakami, M.; Kamimura, D.; Hirano, T. Pleiotropy and specificity: Insights from the interleukin 6 family of cytokines. Immunity, 2019, 50(4), 812-831.
[http://dx.doi.org/10.1016/j.immuni.2019.03.027] [PMID: 30995501]
[20]
Ahmad, M.K.; Abdollah, N.A.; Shafie, N.H.; Yusof, N.M.; Razak, S.R.A. Dual-specificity phosphatase 6 (DUSP6): a review of its molecu-lar characteristics and clinical relevance in cancer. Cancer Biol. Med., 2018, 15(1), 14-28.
[http://dx.doi.org/10.20892/j.issn.2095-3941.2017.0107] [PMID: 29545965]
[21]
Brasseur, K.; Auger, P.; Asselin, E.; Parent, S.; Côté, J.C.; Sirois, M. Parasporin-2 from a new Bacillus thuringiensis 4R2 strain induces caspases activation and apoptosis in human cancer cells. PLoS One, 2015, 10(8), e0135106.
[http://dx.doi.org/10.1371/journal.pone.0135106] [PMID: 26263002]
[22]
Milde-Langosch, K. The Fos family of transcription factors and their role in tumourigenesis. Eur. J. Cancer, 2005, 41(16), 2449-2461.
[http://dx.doi.org/10.1016/j.ejca.2005.08.008] [PMID: 16199154]
[23]
Gschwandtner, M.; Derler, R.; Midwood, K.S. More than just attractive: How CCL2 influences myeloid cell behavior beyond chemotaxis. Front. Immunol., 2019, 10, 2759.
[http://dx.doi.org/10.3389/fimmu.2019.02759] [PMID: 31921102]
[24]
Logan, S.M.; Storey, K.B. Pro-inflammatory AGE-RAGE signaling is activated during arousal from hibernation in ground squirrel adipose. PeerJ, 2018, 6, e4911.
[http://dx.doi.org/10.7717/peerj.4911] [PMID: 29888131]
[25]
Teissier, T.; Boulanger, É. The receptor for advanced glycation end-products (RAGE) is an important pattern recognition receptor (PRR) for inflammaging. Biogerontology, 2019, 20(3), 279-301.
[http://dx.doi.org/10.1007/s10522-019-09808-3] [PMID: 30968282]
[26]
Huang, S.M.; Wu, C.H.; Yen, G.C. Effects of flavonoids on the expression of the pro-inflammatory response in human monocytes in-duced by ligation of the receptor for AGEs. Mol. Nutr. Food Res., 2006, 50(12), 1129-1139.
[http://dx.doi.org/10.1002/mnfr.200600075] [PMID: 17103373]
[27]
Chen, X.; Wang, Z.; Yang, Z.; Wang, J.; Xu, Y.; Tan, R.X.; Li, E. Houttuynia cordata blocks HSV infection through inhibition of NF-κB activation. Antiviral Res., 2011, 92(2), 341-345.
[http://dx.doi.org/10.1016/j.antiviral.2011.09.005] [PMID: 21951655]
[28]
Fanunza, E.; Iampietro, M.; Distinto, S.; Corona, A.; Quartu, M.; Maccioni, E.; Horvat, B.; Tramontano, E. Quercetin blocks ebola virus infection by counteracting the VP24 interferon-inhibitory function. Antimicrob. Agents Chemother., 2020, 64(7), e00530-e20.
[http://dx.doi.org/10.1128/AAC.00530-20] [PMID: 32366711]
[29]
Chiow, K.H.; Phoon, M.C.; Putti, T.; Tan, B.K.; Chow, V.T. Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, querce-tin, quercetrin and cinanserin on murine coronavirus and dengue virus infection. Asian Pac. J. Trop. Med., 2016, 9(1), 1-7.
[http://dx.doi.org/10.1016/j.apjtm.2015.12.002] [PMID: 26851778]
[30]
Luo, E.; Zhang, D.; Luo, H.; Liu, B.; Zhao, K.; Zhao, Y.; Bian, Y.; Wang, Y. Treatment efficacy analysis of traditional Chinese medicine for novel coronavirus pneumonia (COVID-19): an empirical study from Wuhan, Hubei Province, China. Chin. Med., 2020, 15, 34.
[http://dx.doi.org/10.1186/s13020-020-00317-x] [PMID: 32308732]
[31]
Cheng, S.C.; Huang, W.C.; S. Pang, J.H.; Wu, Y.H.; Cheng, C.Y. Quercetin inhibits the production of IL-1β-induced inflammatory cyto-kines and chemokines in ARPE-19 cells via the MAPK and NF-κB signaling pathways. Int. J. Mol. Sci., 2019, 20(12), E2957.
[http://dx.doi.org/10.3390/ijms20122957] [PMID: 31212975]
[32]
Noack, M.; Miossec, P. Selected cytokine pathways in rheumatoid arthritis. Semin. Immunopathol., 2017, 39(4), 365-383.
[http://dx.doi.org/10.1007/s00281-017-0619-z] [PMID: 28213794]
[33]
Ge, Q.; Chen, L.; Tang, M.; Zhang, S.; Liu, L.; Gao, L.; Ma, S.; Kong, M.; Yao, Q.; Feng, F.; Chen, K. Analysis of mulberry leaf compo-nents in the treatment of diabetes using network pharmacology. Eur. J. Pharmacol., 2018, 833, 50-62.
[http://dx.doi.org/10.1016/j.ejphar.2018.05.021] [PMID: 29782863]
[34]
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]
[35]
Palacz-Wrobel, M.; Borkowska, P.; Paul-Samojedny, M.; Kowalczyk, M.; Fila-Danilow, A.; Suchanek-Raif, R.; Kowalski, J. Effect of apig-enin, kaempferol and resveratrol on the gene expression and protein secretion of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) in RAW-264.7 macrophages. Biomed. Pharmacother., 2017, 93, 1205-1212.
[http://dx.doi.org/10.1016/j.biopha.2017.07.054] [PMID: 28738536]
[36]
Li, X.; Bechara, R.; Zhao, J.; McGeachy, M.J.; Gaffen, S.L. IL-17 receptor-based signaling and implications for disease. Nat. Immunol., 2019, 20(12), 1594-1602.
[http://dx.doi.org/10.1038/s41590-019-0514-y] [PMID: 31745337]
[37]
Liu, C.; Liu, H.; Lu, C.; Deng, J.; Yan, Y.; Chen, H.; Wang, Y.; Liang, C.L.; Wei, J.; Han, L.; Dai, Z. Kaempferol attenuates imiquimod-induced psoriatic skin inflammation in a mouse model. Clin. Exp. Immunol., 2019, 198(3), 403-415.
[http://dx.doi.org/10.1111/cei.13363] [PMID: 31407330]
[38]
Ahmad Khan, M.; Sarwar, A.H.M.G.; Rahat, R.; Ahmed, R.S.; Umar, S. Stigmasterol protects rats from collagen induced arthritis by inhib-iting proinflammatory cytokines. Int. Immunopharmacol., 2020, 85, 106642.
[http://dx.doi.org/10.1016/j.intimp.2020.106642] [PMID: 32470883]
[39]
Chen, C.Y.; Kao, C.L.; Liu, C.M. The cancer prevention, anti-inflammatory and anti-oxidation of bioactive phytochemicals targeting the TLR4 signaling pathway. Int. J. Mol. Sci., 2018, 19(9), E2729.
[http://dx.doi.org/10.3390/ijms19092729] [PMID: 30213077]
[40]
Spagnuolo, C.; Moccia, S.; Russo, G.L. Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur. J. Med. Chem., 2018, 153, 105-115.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.001] [PMID: 28923363]
[41]
Kuo, M.Y.; Liao, M.F.; Chen, F.L.; Li, Y.C.; Yang, M.L.; Lin, R.H.; Kuan, Y.H. Luteolin attenuates the pulmonary inflammatory response involves abilities of antioxidation and inhibition of MAPK and NFκB pathways in mice with endotoxin-induced acute lung injury. Food Chem. Toxicol., 2011, 49(10), 2660-2666.
[http://dx.doi.org/10.1016/j.fct.2011.07.012] [PMID: 21782879]

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