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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

Network Pharmacology-based Strategy to Investigate Pharmacological Mechanisms of Qingbutongluo Pill for Treatment of Brucellosis

Author(s): Jing Wang, Jia-Wei He, Ji-Shan Liu, Jian-E Li, Qing-You Cui, Yi-Rui Wang and Wei-Gang Zhou*

Volume 26, Issue 4, 2023

Published on: 26 September, 2022

Page: [706 - 718] Pages: 13

DOI: 10.2174/1386207325666220609121842

Price: $65

Abstract

Background and Objectives: Qingbutongluo pill (QBTLP), a Chinese herbal preparation, has been developed to treat brucellosis for many years with a good therapeutic effect. This study preliminarily explored its potential molecular mechanisms against brucellosis through network pharmacology.

Methods: The active ingredients of QBTLP were screened out mainly from the Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and their potential targets were predicted through the PubChem database and Swiss Target Prediction platform. GeneCards, DisGeNET, Digsee, and the Comparative Toxicogenomics Database (CTD) searched the targets corresponding to brucellosis. Then, the Venn diagram obtained intersection targets of QBTLP and diseases. Protein-protein interaction (PPI) network analysis was performed using the Search Tool for the Retrieval of Interacting Genes database (STRING) and visualized in Cytoscape software. Module analysis of the PPI network and core target identification was performed using the Molecular Complex Detection (MCODE) and the Cytohubba plugins. The Metascape data platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the intersection targets, and then the “active ingredientstargets- pathways” network was constructed using Cytoscape to screen key active ingredients.

Results: 19 key active ingredients were identified by network pharmacological, including Baicalein, Cryptopin, etc. The core targets of QBTLP for treating brucellosis contained TNF, TLR4, MAPK3, MAPK1, MAPK8, MAPK14, MMP9, etc. And the main pathways included the Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, TNF signaling pathway, MAPK signaling pathway, Th17 cell differentiation, and IL-17 signaling pathway.

Conclusions: This study explored the mechanisms of QBTLP for treating brucellosis, which may provide a scientific basis for the clinical application of QBTLP.

Keywords: Qingbutongluo pill, brucellosis, network pharmacology, PPI, cytohubba plugins, signaling pathway.

Graphical Abstract
[1]
National Health Commission of the People’s Republic of China. WS 269-2019, Diagnosis for brucellosis. 2019.
[2]
Wenhong, Z.; Yuexin, Z. Diagnosis and treatment of brucellosis for experts consensus. Chin. J. Infect. Dis, 2017, 35(12), 705-710.
[3]
Ministry of Health of the People’s Republic of China. Diagnosis and treatment guidelines for brucellosis (for trial). Infect. Dis. Info, 2012, 25(6), 323-324.
[4]
Shakir, R. Brucellosis. J. Neurol. Sci., 2021, 420, 117280.
[http://dx.doi.org/10.1016/j.jns.2020.117280] [PMID: 33358192]
[5]
Guan, P.; Wu, W.; Huang, D. Trends of reported human brucellosis cases in mainland China from 2007 to 2017: An exponential smoothing time series analysis. Environ. Health Prev. Med., 2018, 23(1), 23.
[http://dx.doi.org/10.1186/s12199-018-0712-5] [PMID: 29921215]
[6]
Wang, D.S.; Zhao, T.Y.; He, Q.; Xi, J.X.; Wang, X.R.; Guan, H.; Zhou, X.Y.; Zhao, Q. Discussion on the rules of syndrome differentiation and treatment of brucellosis. Chin. J. Ctrl. Endem Dis, 2020, 35(3), 217-219.
[7]
Xu, Z.R.; Zheng, A.H. Current status of Chinese medicine treatment of brucellosis. Chinese Med., 2016, 31(02), 301-303.
[8]
He, D.F. Discussion on the pharmacological action of traditional Chinese medicine in the treatment of Chronic brucellosis. Guide China Med., 2015, (14), 296-297.
[9]
Zhang, Z.G.; Sun, R.Z.; Zhang, L.J. The pharmacological action of traditional Chinese medicine in the treatment of Chronic brucellosis. Chin. J. Ctrl. Endem. Dis, 2007, 22(005), 380-382.
[10]
Zhang, S.Y. Research advances of the treatment for brucellosis in China. Chin. J. Ctrl. Endem. Dis, 1993, (1), 52-54.
[11]
Brucellosis Study Group of Institute for Epidemic Disease Control and Preventive of Chinese Academy of Medical Sciences. Chinese medicines of promoting blood circulation and removing blood stasis in the treatment of Chronic brucellosis. J. Med. Res., 1974, (11), 6-7.
[12]
Zhu, Z.; Chen, A.L.; Peng, D.; Min, X.; Chen, Z.H. Advances in diagnosis and treatment of brucellosis. Shandong Yiyao, 2017, (07), 104-107.
[13]
Shu, Z.H.; Ding, Q.G.; Sun, M.; Wang, L.T.; Xuan, J. Diagnostic norms of traditional Chinese medicine for arthralgia. World Latest Med. Inform., 2019, 19(72), 233-234.
[14]
Li, M. A traditional Chinese medicine composition for treating brucellosis and its preparation method: China, 2018, 201711479506.5.
[15]
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 database 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]
[16]
Xue, R.; Fang, Z.; Zhang, M.; Yi, Z.; Wen, C.; Shi, T. TCMID: Traditional Chinese Medicine Integrative Database for herb molecular mechanism analysis. Nucleic Acids Res., 2013, 41(Database issue), D1089-D1095.
[PMID: 23203875]
[17]
Xu, H.Y.; Zhang, Y.Q.; Liu, Z.M.; Chen, T.; Lv, C.Y.; Tang, S.H.; Zhang, X.B.; Zhang, W.; Li, Z.Y.; Zhou, R.R.; Yang, H.J.; Wang, X.J.; Huang, L.Q. ETCM: An encyclopaedia of traditional Chinese medicine. Nucleic Acids Res., 2019, 47(D1), D976-D982.
[http://dx.doi.org/10.1093/nar/gky987] [PMID: 30365030]
[18]
Liu, Z.; Guo, F.; Wang, Y.; Li, C.; Zhang, X.; Li, H.; Diao, L.; Gu, J.; Wang, W.; Li, D.; He, F. BATMAN-TCM: A bioinformatics analysis tool for molecular mechanism of traditional chinese medicine. Sci. Rep., 2016, 6, 21146.
[http://dx.doi.org/10.1038/srep21146] [PMID: 26879404]
[19]
Shanghai Institute of Organic Chemistry of CAS. Chemistry Database [DB/OL]., Available from: http://www.organchem.csdb.cn [1978-2020].
[20]
Daina, A.; Michielin, O.; Zoete, V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7, 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[21]
Kim, S.; Thiessen, P.A.; Bolton, E.E.; Chen, J.; Fu, G.; Gindulyte, A.; Han, L.; He, J.; He, S.; Shoemaker, B.A.; Wang, J.; Yu, B.; Zhang, J.; Bryant, S.H. PubChem substance and compound databases. Nucleic Acids Res., 2016, 44(D1), D1202-D1213.
[http://dx.doi.org/10.1093/nar/gkv951] [PMID: 26400175]
[22]
Daina, A.; Michielin, O.; Zoete, V. SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res., 2019, 47(W1), W357-W364.
[http://dx.doi.org/10.1093/nar/gkz382] [PMID: 31106366]
[23]
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, baq020.
[http://dx.doi.org/10.1093/database/baq020] [PMID: 20689021]
[24]
Piñero, J.; Queralt-Rosinach, N.; Bravo, À.; Deu-Pons, J.; Bauer-Mehren, A.; Baron, M.; Sanz, F.; Furlong, L.I. DisGeNET: A discovery platform for the dynamical exploration of human diseases and their genes. Database (Oxford), 2015, 2015, bav028.
[http://dx.doi.org/10.1093/database/bav028] [PMID: 25877637]
[25]
Kim, J.; So, S.; Lee, H.J.; Park, J.C.; Kim, J.J.; Lee, H. DigSee: Disease gene search engine with evidence sentences (version cancer). Nucleic Acids Res., 2013, 41(Web Server issue), W510-7.
[http://dx.doi.org/10.1093/nar/gkt531] [PMID: 23761452]
[26]
Davis, A.P.; Grondin, C.J.; Johnson, R.J.; Sciaky, D.; McMorran, R.; Wiegers, J.; Wiegers, T.C.; Mattingly, C.J. The comparative toxicogenomics database: Update 2019. Nucleic Acids Res., 2019, 47(D1), D948-D954.
[http://dx.doi.org/10.1093/nar/gky868] [PMID: 30247620]
[27]
Amberger, J.S.; Bocchini, C.A.; Schiettecatte, F.; Scott, A.F.; Hamosh, A. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res., 2015, 43(Database issue), D789-D798.
[http://dx.doi.org/10.1093/nar/gku1205] [PMID: 25428349]
[28]
Wishart, D.S.; Feunang, Y.D.; Guo, A.C.; Lo, E.J.; Marcu, A.; Grant, J.R.; Sajed, T.; Johnson, D.; Li, C.; Sayeeda, Z.; Assempour, N.; Iynkkaran, I.; Liu, Y.; Maciejewski, A.; Gale, N.; Wilson, A.; Chin, L.; Cummings, R.; Le, D.; Pon, A.; Knox, C.; Wilson, M. DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Res., 2018, 46(D1), D1074-D1082.
[http://dx.doi.org/10.1093/nar/gkx1037] [PMID: 29126136]
[29]
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]
[30]
Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[31]
Chin, C.H.; Chen, S.H.; Wu, H.H.; Ho, C.W.; Ko, M.T.; Lin, C.Y. cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC. Syst. Biol., 2014, 8(Suppl. 4), S11.
[32]
Zhou, Y.; Zhou, B.; Pache, L.; Chang, M.; Khodabakhshi, A.H.; Tanaseichuk, O.; Benner, C.; Chanda, S.K. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun., 2019, 10(1), 1523.
[http://dx.doi.org/10.1038/s41467-019-09234-6] [PMID: 30944313]
[33]
Qin, S.M.; Lin, J.Y.; Huang, K.E. Immune regulation effects of astragali radix. Zhonghua Zhongyiyao Xuekan, 2017, 035(003), 699-702.
[34]
Fan, C.Z.; Hong, Q.Y. Study on modern pharmacological research development of Codonopsis pilosula in human body system function. China Medical Herald, 2016, 13(10), 39-43.
[35]
Liu, G.X.; Qin, J.; Yu, B.Y. Research progress on the pharmacological activity of Codonopsis pilosula. Strait Pharmaceutical Journal, 2018, 30(011), 36-39.
[36]
Chen, D.M.; Meng, J.; Liu, J.J.; Zhao, Y.; Wang, J. Network pharmacology-based study on mechanism of Codonopsis pilosula enhancing immune function. Chinese Archiv. Trad. Chinese Med., 2020, 38(02), 192-195.
[37]
Chinese Pharmacopoeia Commission. Chinese Pharmacopoeia China Medical Science Press: Beijing, 2020; I, pp. 39-40.
[38]
Zhou, L.P. Study on the patterns of compatibility and treatment features of prescriptions containing Bupleuri Radix-Scutellariae Radix during past dynasties; Nanjing University of Chinese Medicine: Nanjing, 2019.
[39]
Infectious Diseases Teaching and Research Group in Department of Veterinary Medicine. Research on traditional Chinese medicine in the treatment of brucellosis I the antibacterial action of 142 kinds of traditional Chinese medicine for 3 types of Brucella spp. in vitro. Gansu Nongye Daxue Xuebao, 1961, (2), 37-41.
[40]
Zhao, Q.; Chen, X.Y.; Martin, C. Scutellaria baicalensis, the golden herb from the garden of Chinese medicinal plants. Sci. Bull. (Beijing), 2016, 61(18), 1391-1398.
[http://dx.doi.org/10.1007/s11434-016-1136-5] [PMID: 27730005]
[41]
Yun, B.Y.; Zhou, L.; Xie, K.P.; Wang, Y.J.; Xie, M.J. Antibacterial activity and mechanism of baicalein. Yao Xue Xue Bao, 2012, 47(12), 1587-1592.
[PMID: 23460962]
[42]
Yang, D.; Hu, H.; Huang, S.; Chaumont, J.P.; Millet, J. Studies on the inhibitory effects of baicalein and baicalin on skin fungi and bacteria. Zhong Yao Cai, 2000, 23(005), 272-274.
[PMID: 12575154]
[43]
Wu, T.; He, M.; Zang, X.; Zhou, Y.; Qiu, T.; Pan, S.; Xu, X. A structure-activity relationship study of flavonoids as inhibitors of E. coli by membrane interaction effect. Biochim. Biophys. Acta, 2013, 1828(11), 2751-2756.
[http://dx.doi.org/10.1016/j.bbamem.2013.07.029] [PMID: 23938956]
[44]
Chinnam, N.; Dadi, P.K.; Sabri, S.A.; Ahmad, M.; Kabir, M.A.; Ahmad, Z. Dietary bioflavonoids inhibit Escherichia coli ATP synthase in a differential manner. Int. J. Biol. Macromol., 2010, 46(5), 478-486.
[http://dx.doi.org/10.1016/j.ijbiomac.2010.03.009] [PMID: 20346967]
[45]
Zhou, L.G.; Zhang, Y.J.; Cai, Y.; Liu, Y.Q.; Wang, J.L.; Wang, J.J. Antifungal activity of Flavonoids and steroids compounds. Nat. Prot. Res. De, 1997, 9(03), 24-29.
[46]
Huang, S. Mechanism study of baicalein against Candida albicans; Second Military Medical University: Shanghai, 2009.
[47]
Goc, A.; Niedzwiecki, A.; Rath, M. In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia burgdorferi and Borrelia garinii. J. Appl. Microbiol., 2015, 119(6), 1561-1572.
[http://dx.doi.org/10.1111/jam.12970] [PMID: 26457476]
[48]
Chen, Y.; Liu, T.; Wang, K.; Hou, C.; Cai, S.; Huang, Y.; Du, Z.; Huang, H.; Kong, J.; Chen, Y. Baicalein inhibits Staphylococcus aureus biofilm formation and the quorum sensing system in vitro. PLoS One, 2016, 11(4), e0153468.
[http://dx.doi.org/10.1371/journal.pone.0153468] [PMID: 27128436]
[49]
Luo, J.; Kong, J.L.; Dong, B.Y.; Huang, H.; Wang, K.; Wu, L.H.; Hou, C.C.; Liang, Y.; Li, B.; Chen, Y.Q. Baicalein attenuates the quorum sensing-controlled virulence factors of Pseudomonas aeruginosa and relieves the inflammatory response in P. aeruginosa-infected macrophages by downregulating the MAPK and NFκB signal-transduction pathways. Drug Des. Devel. Ther., 2016, 10, 183-203.
[http://dx.doi.org/10.2147/DDDT.S97221] [PMID: 26792984]
[50]
Cao, Y.; Dai, B.; Wang, Y.; Huang, S.; Xu, Y.; Cao, Y.; Gao, P.; Zhu, Z.; Jiang, Y. In vitro activity of baicalein against Candida albicans biofilms. Int. J. Antimicrob. Agents, 2008, 32(1), 73-77.
[http://dx.doi.org/10.1016/j.ijantimicag.2008.01.026] [PMID: 18374543]
[51]
Liu, L.; Lin, H.; Huang, R.S.; Sun, P.H.; Guo, J.L. Study on inhibitory effect of baicalin and baicalein on the formation of streptococcus mutans biofilm. Zhongyao Xinyao Yu Linchuang Yaoli, 2017, 28(4), 464-467.
[52]
Zeng, Z.; Qian, L.; Cao, L.; Tan, H.; Huang, Y.; Xue, X.; Shen, Y.; Zhou, S. Virtual screening for novel quorum sensing inhibitors to eradicate biofilm formation of Pseudomonas aeruginosa. Appl. Microbiol. Biotechnol., 2008, 79(1), 119-126.
[http://dx.doi.org/10.1007/s00253-008-1406-5] [PMID: 18330563]
[53]
Tsou, L.K.; Lara-Tejero, M.; RoseFigura, J.; Zhang, Z.J.; Wang, Y.C.; Yount, J.S.; Lefebre, M.; Dossa, P.D.; Kato, J.; Guan, F.; Lam, W.; Cheng, Y.C.; Galán, J.E.; Hang, H.C. Antibacterial flavonoids from medicinal plants covalently inactivate type III protein secretion substrates. J. Am. Chem. Soc., 2016, 138(7), 2209-2218.
[http://dx.doi.org/10.1021/jacs.5b11575] [PMID: 26847396]
[54]
Vinh, P.T.; Shinohara, Y.; Yamada, A.; Duc, H.M.; Nakayama, M.; Ozawa, T.; Sato, J.; Masuda, Y.; Honjoh, K.I.; Miyamoto, T. Baicalein Inhibits Stx1 and 2 of EHE: Effects of baicalein on the cytotoxicity, production, and secretion of shiga toxins of enterohaemorrhagic Escherichia coli. Toxins (Basel), 2019, 11(9), 505.
[http://dx.doi.org/10.3390/toxins11090505] [PMID: 31470657]
[55]
Qian, M.; Tang, S.; Wu, C.; Wang, Y.; He, T.; Chen, T.; Xiao, X. Synergy between baicalein and penicillins against penicillinase-producing Staphylococcus aureus. Int. J. Med. Microbiol., 2015, 305(6), 501-504.
[http://dx.doi.org/10.1016/j.ijmm.2015.05.001] [PMID: 26028441]
[56]
Fujita, M.; Shiota, S.; Kuroda, T.; Hatano, T.; Yoshida, T.; Mizushima, T.; Tsuchiya, T. Remarkable synergies between baicalein and tetracycline, and baicalein and beta-lactams against methicillin-resistant Staphylococcus aureus. Microbiol. Immunol., 2005, 49(4), 391-396.
[http://dx.doi.org/10.1111/j.1348-0421.2005.tb03732.x] [PMID: 15840965]
[57]
Chan, B.C.; Ip, M.; Lau, C.B.; Lui, S.L.; Jolivalt, C.; Ganem-Elbaz, C.; Litaudon, M.; Reiner, N.E.; Gong, H.; See, R.H.; Fung, K.P.; Leung, P.C. Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase. J. Ethnopharmacol., 2011, 137(1), 767-773.
[http://dx.doi.org/10.1016/j.jep.2011.06.039] [PMID: 21782012]
[58]
Chang, P.C.; Li, H.Y.; Tang, H.J.; Liu, J.W.; Wang, J.J.; Chuang, Y.C. In vitro synergy of baicalein and gentamicin against vancomycin-resistant Enterococcus. J. Microbiol. Immunol. Infect., 2007, 40(1), 56-61.
[PMID: 17332908]
[59]
Lu, H.; Li, X.; Wang, G.; Wang, C.; Feng, J.; Lu, W.; Wang, X.; Chen, H.; Liu, M.; Tan, C. Baicalein ameliorates Streptococcus suis-induced infection in vitro and in vivo. Int. J. Mol. Sci., 2021, 22(11), 5829.
[http://dx.doi.org/10.3390/ijms22115829] [PMID: 34072443]
[60]
Cai, W.; Fu, Y.; Zhang, W.; Chen, X.; Zhao, J.; Song, W.; Li, Y.; Huang, Y.; Wu, Z.; Sun, R.; Dong, C.; Zhang, F. Synergistic effects of baicalein with cefotaxime against Klebsiella pneumoniae through inhibiting CTX-M-1 gene expression. BMC Microbiol., 2016, 16(1), 181.
[http://dx.doi.org/10.1186/s12866-016-0797-1] [PMID: 27502110]
[61]
Fu, Z.; Lu, H.; Zhu, Z.; Yan, L.; Jiang, Y.; Cao, Y. Combination of baicalein and Amphotericin B accelerates Candida albicans apoptosis. Biol. Pharm. Bull., 2011, 34(2), 214-218.
[http://dx.doi.org/10.1248/bpb.34.214] [PMID: 21415530]
[62]
Zhao, L.Y.; Jiang, J.C.; Yao, X.W.; Cao, Y.Y.; Jiang, Y.Y. Synergistic effect of baicalein in combination with fluconazole on Candida albicans biofilm. Chin. J. Mycol, 2014, 9(002), 70-74.
[63]
Goc, A.; Niedzwiecki, A.; Rath, M. Cooperation of doxycycline with phytochemicals and micronutrients against active and persistent forms of borrelia sp. Int. J. Biol. Sci., 2016, 12(9), 1093-1103.
[http://dx.doi.org/10.7150/ijbs.16060] [PMID: 27570483]
[64]
Chen, W.P. The anti-osteoarthritic properties and corresponding molecular mechanisms of baicalein; Zhejiang University: Zhejiang, 2011.
[65]
Dinda, B.; Dinda, S.; DasSharma, S.; Banik, R.; Chakraborty, A.; Dinda, M. Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders. Eur. J. Med. Chem., 2017, 131, 68-80.
[http://dx.doi.org/10.1016/j.ejmech.2017.03.004] [PMID: 28288320]
[66]
Liang, C.; Wei, Wei; Liang, X.W.; De, E.J.; LiWangang, L.J. Research progress of osteoarticular involvement with brucellosis. Chin. J. Zoonoses, 2018, 034(012), 1147-1150.
[67]
Li, J.B.; Wang, Y.J.; Liu, J.; Zhang, S.K. Advances in research on the pathogenesis of osteoarticular brucellosis. Zhonghua Difangbingxue Zazhi, 2019, 38(12), 1019-1022.
[68]
Fagn, Y.P.; Zhang, L.B. Advances in brucellosis with osteoarthritis. Zhonghua Difangbingxue Zazhi, 2019, 38(5), 426-430.
[69]
Alles, G.A.; Ellis, C.H. A comparative study of the pharmacology of certain cryptopine alkaloids. J. Pharmacol. Exp. Ther., 1952, 104(3), 253-263.
[PMID: 14908893]
[70]
Dorneles, E.M.; Teixeira-Carvalho, A.; Araújo, M.S.; Sriranganathan, N.; Lage, A.P. Immune response triggered by Brucella abortus following infection or vaccination. Vaccine, 2015, 33(31), 3659-3666.
[http://dx.doi.org/10.1016/j.vaccine.2015.05.057] [PMID: 26048781]
[71]
Hu, Y.; Xu, X.Q. Advances in molecular mechanisms of recognition and regulation of innate immunity. Zhongguo Zhongliu Shengwu Zhiliao Zazhi, 2013, 20(4), 485-492.
[72]
Arias, M.A.; Santiago, L.; Costas-Ramon, S.; Jaime-Sánchez, P.; Freudenberg, M.; Jiménez De Bagüés, M.P.; Pardo, J. Toll-like receptors 2 and 4 cooperate in the control of the emerging pathogen Brucella microti. Front. Cell. Infect. Microbiol., 2017, 6, 205.
[http://dx.doi.org/10.3389/fcimb.2016.00205] [PMID: 28119856]
[73]
Zhao, R.R.; Li, M.; Yue, W.; Yuan, H.; Miao, X.R. Research progress in the immune mechanisms of chronic brucellosis. Chin. J. Infect Dis, 2019, 37(9), 573-576.
[74]
Kawai, T.; Akira, S. TLR signaling. Semin. Immunol., 2007, 19(1), 24-32.
[http://dx.doi.org/10.1016/j.smim.2006.12.004] [PMID: 17275323]
[75]
Campos, M.A.; Rosinha, G.M.; Almeida, I.C.; Salgueiro, X.S.; Jarvis, B.W.; Splitter, G.A.; Qureshi, N.; Bruna-Romero, O.; Gazzinelli, R.T.; Oliveira, S.C. Role of Toll-like receptor 4 in induction of cell-mediated immunity and resistance to Brucella abortus infection in mice. Infect. Immun., 2004, 72(1), 176-186.
[http://dx.doi.org/10.1128/IAI.72.1.176-186.2004] [PMID: 14688095]
[76]
Lee, J.J.; Kim, D.H.; Kim, D.G.; Lee, H.J.; Min, W.; Rhee, M.H.; Cho, J.Y.; Watarai, M.; Kim, S. Toll-like receptor 4-linked Janus kinase 2 signaling contributes to internalization of Brucella abortus by macrophages. Infect. Immun., 2013, 81(7), 2448-2458.
[http://dx.doi.org/10.1128/IAI.00403-13] [PMID: 23630962]
[77]
Im, Y.B.; Park, W.B.; Jung, M.; Kim, S.; Yoo, H.S. Evaluation of Th1/Th2-related immune response against recombinant proteins of Brucella abortus infection in mice. J. Microbiol. Biotechnol., 2016, 26(6), 1132-1139.
[http://dx.doi.org/10.4014/jmb.1512.12046] [PMID: 27012238]
[78]
Gao, G.; Xu, J. Important biology events and pathways in Brucella infection and implications for novel antibiotic drug targets. Crit. Rev. Eukaryot. Gene Expr., 2013, 23(1), 65-76.
[http://dx.doi.org/10.1615/CritRevEukarGeneExpr.2013006580] [PMID: 23557338]
[79]
Gomes, M.T.; Campos, P.C.; Pereira, Gde.S.; Bartholomeu, D.C.; Splitter, G.; Oliveira, S.C. TLR9 is required for MAPK/NF-κB activation but does not cooperate with TLR2 or TLR6 to induce host resistance to Brucella abortus. J. Leukoc. Biol., 2016, 99(5), 771-780.
[http://dx.doi.org/10.1189/jlb.4A0815-346R] [PMID: 26578650]
[80]
Vieira, A.L.; Silva, T.M.; Mol, J.P.; Oliveira, S.C.; Santos, R.L.; Paixão, T.A. MyD88 and TLR9 are required for early control of Brucella ovis infection in mice. Res. Vet. Sci., 2013, 94(3), 399-405.
[http://dx.doi.org/10.1016/j.rvsc.2012.10.028] [PMID: 23218066]
[81]
Gomes, M.T.; Campos, P.C.; Oliveira, F.S.; Corsetti, P.P.; Bortoluci, K.R.; Cunha, L.D.; Zamboni, D.S.; Oliveira, S.C. Critical role of ASC inflammasomes and bacterial type IV secretion system in caspase-1 activation and host innate resistance to Brucella abortus infection. J. Immunol., 2013, 190(7), 3629-3638.
[http://dx.doi.org/10.4049/jimmunol.1202817] [PMID: 23460746]
[82]
Campos, P.C.; Gomes, M.T.R.; Marinho, F.A.V.; Guimarães, E.S.; de Moura Lodi Cruz, M.G.F.; Oliveira, S.C. Brucella abortus nitric oxide metabolite regulates inflammasome activation and IL-1β secretion in murine macrophages. Eur. J. Immunol., 2019, 49(7), 1023-1037.
[http://dx.doi.org/10.1002/eji.201848016] [PMID: 30919410]
[83]
Marim, F.M.; Franco, M.M.C.; Gomes, M.T.R.; Miraglia, M.C.; Giambartolomei, G.H.; Oliveira, S.C. The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection. Semin. Immunopathol., 2017, 39(2), 215-223.
[http://dx.doi.org/10.1007/s00281-016-0581-1] [PMID: 27405866]
[84]
Kelley, N.; Jeltema, D.; Duan, Y.; He, Y. The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. Int. J. Mol. Sci., 2019, 20(13), 3328.
[http://dx.doi.org/10.3390/ijms20133328] [PMID: 31284572]
[85]
Chen, G.; Goeddel, D.V. TNF-R1 signaling: A beautiful pathway. Science, 2002, 296(5573), 1634-1635.
[http://dx.doi.org/10.1126/science.1071924] [PMID: 12040173]
[86]
Billard, E.; Dornand, J.; Gross, A. Brucella suis prevents human dendritic cell maturation and antigen presentation through regulation of tumor necrosis factor alpha secretion. Infect. Immun., 2007, 75(10), 4980-4989.
[http://dx.doi.org/10.1128/IAI.00637-07] [PMID: 17635859]
[87]
Martirosyan, A.; Gorvel, J.P. Brucella evasion of adaptive immunity. Future Microbiol., 2013, 8(2), 147-154.
[http://dx.doi.org/10.2217/fmb.12.140] [PMID: 23374122]
[88]
Sabio, G.; Davis, R.J. TNF and MAP kinase signalling pathways. Semin. Immunol., 2014, 26(3), 237-245.
[http://dx.doi.org/10.1016/j.smim.2014.02.009] [PMID: 24647229]
[89]
Gomes, M.T.; Campos, P.C.; de Almeida, L.A.; Oliveira, F.S.; Costa, M.M.; Marim, F.M.; Pereira, G.S.; Oliveira, S.C. The role of innate immune signals in immunity to Brucella abortus. Front. Cell. Infect. Microbiol., 2012, 2, 130.
[http://dx.doi.org/10.3389/fcimb.2012.00130] [PMID: 23112959]
[90]
Oliveira, F.S.; Carvalho, N.B.; Brandão, A.P.; Gomes, M.T.; de Almeida, L.A.; Oliveira, S.C. Interleukin-1 receptor-associated kinase 4 is essential for initial host control of Brucella abortus infection. Infect. Immun., 2011, 79(11), 4688-4695.
[http://dx.doi.org/10.1128/IAI.05289-11] [PMID: 21844234]
[91]
Huy, T.X.N.; Reyes, A.W.B.; Hop, H.T.; Arayan, L.T.; Son, V.H.; Min, W.; Lee, H.J.; Kim, S. Emodin successfully inhibited invasion of Brucella abortus via modulting adherence, microtubule dynamics and ERK signaling pathway in raw 264.7 Cells. J. Microbiol. Biotechnol., 2018, 28(10), 1723-1729.
[http://dx.doi.org/10.4014/jmb.1804.04040] [PMID: 30196590]
[92]
Reyes, A.W.; Arayan, L.T.; Simborio, H.L.; Hop, H.T.; Min, W.; Lee, H.J.; Kim, D.H.; Chang, H.H.; Kim, S. Dextran sulfate sodium upregulates MAPK signaling for the uptake and subsequent intracellular survival of Brucella abortus in murine macrophages. Microb. Pathog., 2016, 91, 68-73.
[http://dx.doi.org/10.1016/j.micpath.2015.10.024] [PMID: 26626959]
[93]
Cargnello, M.; Roux, P.P. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol. Mol. Biol. Rev., 2011, 75(1), 50-83.
[http://dx.doi.org/10.1128/MMBR.00031-10] [PMID: 21372320]
[94]
Cuadrado, A.; Nebreda, A.R. Mechanisms and functions of p38 MAPK signalling. Biochem. J., 2010, 429(3), 403-417.
[http://dx.doi.org/10.1042/BJ20100323] [PMID: 20626350]
[95]
Oukka, M. Th17 cells in immunity and autoimmunity. Ann. Rheum. Dis., 2008, 67(Suppl. 3), iii26-iii29.
[http://dx.doi.org/10.1136/ard.2008.098004]
[96]
Ivanov, I.I.; Zhou, L.; Littman, D.R. Transcriptional regulation of Th17 cell differentiation. Semin. Immunol., 2007, 19(6), 409-417.
[http://dx.doi.org/10.1016/j.smim.2007.10.011] [PMID: 18053739]
[97]
Luckheeram, R.V.; Zhou, R.; Verma, A.D.; Xia, B. CD4⁺T cells: Differentiation and functions. Clin. Dev. Immunol., 2012, 2012, 925135.
[http://dx.doi.org/10.1155/2012/925135] [PMID: 22474485]
[98]
Yasuda, K.; Takeuchi, Y.; Hirota, K. The pathogenicity of Th17 cells in autoimmune diseases. Semin. Immunopathol., 2019, 41(3), 283-297.
[http://dx.doi.org/10.1007/s00281-019-00733-8] [PMID: 30891627]
[99]
Gu, C.; Wu, L.; Li, X. IL-17 family: Cytokines, receptors and signaling. Cytokine, 2013, 64(2), 477-485.
[http://dx.doi.org/10.1016/j.cyto.2013.07.022] [PMID: 24011563]
[100]
Curtis, M.M.; Way, S.S. Interleukin-17 in host defence against bacterial, mycobacterial and fungal pathogens. Immunology, 2009, 126(2), 177-185.
[http://dx.doi.org/10.1111/j.1365-2567.2008.03017.x] [PMID: 19125888]
[101]
Vitry, M.A.; De Trez, C.; Goriely, S.; Dumoutier, L.; Akira, S.; Ryffel, B.; Carlier, Y.; Letesson, J.J.; Muraille, E. Crucial role of gamma interferon-producing CD4+ Th1 cells but dispensable function of CD8+ T cell, B cell, Th2, and Th17 responses in the control of Brucella melitensis infection in mice. Infect. Immun., 2012, 80(12), 4271-4280.
[http://dx.doi.org/10.1128/IAI.00761-12] [PMID: 23006848]
[102]
Clapp, B.; Skyberg, J.A.; Yang, X.; Thornburg, T.; Walters, N.; Pascual, D.W. Protective live oral brucellosis vaccines stimulate Th1 and th17 cell responses. Infect. Immun., 2011, 79(10), 4165-4174.
[http://dx.doi.org/10.1128/IAI.05080-11] [PMID: 21768283]
[103]
Pasquevich, K.A.; Ibañez, A.E.; Coria, L.M.; García Samartino, C.; Estein, S.M.; Zwerdling, A.; Barrionuevo, P.; Oliveira, F.S.; Seither, C.; Warzecha, H.; Oliveira, S.C.; Giambartolomei, G.H.; Cassataro, J. An oral vaccine based on U-Omp19 induces protection against B. Abortus mucosal challenge by inducing an adaptive IL-17 immune response in mice. PLoS One, 2011, 6(1), e16203.
[http://dx.doi.org/10.1371/journal.pone.0016203] [PMID: 21264260]
[104]
Abkar, M.; Fasihi-Ramandi, M.; Kooshki, H.; Sahebghadam Lotfi, A. Oral immunization of mice with Omp31-loaded N-trimethyl chitosan nanoparticles induces high protection against Brucella melitensis infection. Int. J. Nanomedicine, 2017, 12, 8769-8778.
[http://dx.doi.org/10.2147/IJN.S149774] [PMID: 29263667]
[105]
Zheng, R.; Xie, S.; Zhang, Q.; Cao, L.; Niyazi, S.; Lu, X.; Sun, L.; Zhou, Y.; Zhang, Y.; Wang, K. Circulating Th1, Th2, Th17, Treg, and PD-1 levels in patients with brucellosis. J. Immunol. Res., 2019, 2019, 3783209.
[http://dx.doi.org/10.1155/2019/3783209] [PMID: 31467933]

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