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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

Analysis of Herbal Mechanisms and Prescriptions for Chronic Cerebral Circulatory Insufficiency Based on Data Mining and Network Pharmacology

Author(s): Ying Yu, Gong Zhang, Tao Han* and Hai-liang Huang*

Volume 25, Issue 8, 2022

Published on: 12 January, 2022

Page: [1239 - 1253] Pages: 15

DOI: 10.2174/1386207324999210120194312

Price: $65

Abstract

Background: Traditional Chinese medicine has accumulated rich resources and experience through clinical research to explore the prevention and treatment of chronic cerebral circulatory insufficiency, but current medicine lacks in-depth research and confirmation on the established protocols and mechanism of prescribed TCMs at the macro and micro levels.

Objective: To explore the prescription of Chinese medicines for the treatment of Chronic Cerebral Circulation Insufficiency (CCCI) and to explore the mechanism of core drugs.

Methods: 229 Chinese prescriptions for CCCI were collected from CNKI, CBM, VIP and WANFANG databases for this study. The frequency and association rules of drugs were analyzed and the core drugs by TCMISSV2.5 software was extracted. The active ingredients and targets were obtained by TCMSP, and genes of CCCI were collected from the DisGeNET, OMIM, DrugBank disease databases. The intersection targets of herbal medicine and disease were imported into the STRING database for PPI network. The key targets were screened by the network topology algorithm. The Systems Dock website was used to verify the molecular docking. The GOEAST and DAVID tools were used to perform GO and KEGG pathway analysis with the key target genes.

Results: 117 drugs involved in 229 prescriptions were identified, 2 core drugs were identified. We identified 8 active ingredients, which were mandenol, myricanone, perlolyrine, senkyunone, wallichilide, sitosterol, beta-sitosterol and stigmasterol. 371 herbal targets predicted and 335 disease targets. The enrichment analysis showed that the core herbal medicines could prevent CCCI by 15 key signaling pathways.

Conclusion: There are direct or indirect connections in key signaling pathways, which not only participate in energy metabolism, hormone regulation, signal transduction, but also play a role in the comprehensive intervention of nervous system, immune system, circulatory system and other systems, which is consistent with the comprehensive pathogenesis of CCCI induced by multiple factors.

Keywords: Traditional chinese medicine, chronic cerebral insufficiency, data mining, network pharmacology, medication rule, mechanism of action.

Graphical Abstract
[1]
Wormald, P.J. The agger nasi cell: the key to understanding the anatomy of the frontal recess. Otolaryngol. Head Neck Surg., 2003, 129(5), 497-507.
[http://dx.doi.org/10.1016/S0194-5998(03)01581-X] [PMID: 14595272]
[2]
Zhou, D.; Meng, R.; Li, S.J.; Ya, J.Y.; Ding, J.Y.; Shang, S.L.; Ding, Y.C.; Ji, X.M. Advances in chronic cerebral circulation insufficiency. CNS Neurosci. Ther., 2018, 24(1), 5-17.
[http://dx.doi.org/10.1111/cns.12780] [PMID: 29143463]
[3]
Baohong, T. Research status of etiology and pathogenesis of chronic cerebral insufficiency. Acta Chinese Med., 2010, 25(3), 430-432.
[http://dx.doi.org/10.16368/j.issn.1674-8999.2010.03.052]
[4]
Peng, L.; Jian, L.; Shihuan, T.; Jianxin, C.; Xiaohan, Z.; Xi, L.; Shaoxin, W.; Yibo, G.; Hongjun, Y. Development and application of traditional Chinese Medicine Inheritance support system. Zhongguo Shiyan Fangjixue Zazhi, 2012, 18(9), 1-4.
[http://dx.doi.org/10.13422/j.cnki.syfjx.2012.09.018]
[5]
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]
[6]
Jinlong, R. Construction and application of pharmacology database and analysis platform of traditional Chinese medicine system. J. Northwest A&F Univ., 2015, Available from: https://x.cnki.net/kcms/detail/detail.aspx?filename=1015332723.nh&dbcode=CMFD&dbname=CMFD2016&v=
[7]
Keiser, M.J.; Roth, B.L.; Armbruster, B.N.; Ernsberger, P.; Irwin, J.J.; Shoichet, B.K. Relating protein pharmacology by ligand chemistry. Nat. Biotechnol., 2007, 25(2), 197-206.
[http://dx.doi.org/10.1038/nbt1284] [PMID: 17287757]
[8]
Daina, A.; Michielin, O.; Zoete, V. Swiss Target Prediction: 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]
[9]
Gfeller, D.; Michielin, O.; Zoete, V. Shaping the interaction landscape of bioactive molecules. Bioinformatics, 2013, 29(23), 3073-3079.
[http://dx.doi.org/10.1093/bioinformatics/btt540] [PMID: 24048355]
[10]
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.
[http://dx.doi.org/10.1093/database/bav028] [PMID: 25877637]
[11]
Piñero, J.; Bravo, À.; Queralt-Rosinach, N.; Gutiérrez-Sacristán, A.; Deu-Pons, J.; Centeno, E.; García-García, J.; Sanz, F.; Furlong, L.I. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res., 2017, 45(D1), D833-D839.
[http://dx.doi.org/10.1093/nar/gkw943] [PMID: 27924018]
[12]
Hamosh, A.; Scott, A.F.; Amberger, J.S.; Bocchini, C.A.; McKusick, V.A. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res., 2005, 33(Database issue), D514-D517.
[http://dx.doi.org/10.1093/nar/gki033] [PMID: 15608251]
[13]
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]
[14]
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(1), 607-613.
[http://dx.doi.org/10.1093/nar/gky1131]
[15]
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]
[16]
Burley, S.K.; Berman, H.M.; Bhikadiya, C.; Bi, C.; Chen, L.; Di Costanzo, L.; Christie, C.; Dalenberg, K.; Duarte, J.M.; Dutta, S.; Feng, Z.; Ghosh, S.; Goodsell, D.S.; Green, R.K.; Guranovic, V.; Guzenko, D.; Hudson, B.P.; Kalro, T.; Liang, Y.; Lowe, R.; Namkoong, H.; Peisach, E.; Periskova, I.; Prlic, A.; Randle, C.; Rose, A.; Rose, P.; Sala, R.; Sekharan, M.; Shao, C.; Tan, L.; Tao, Y.P.; Valasatava, Y.; Voigt, M.; Westbrook, J.; Woo, J.; Yang, H.; Young, J.; Zhuravleva, M.; Zardecki, C. RCSB Protein Data Bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy. Nucleic Acids Res., 2019, 47(D1), D464-D474.
[http://dx.doi.org/10.1093/nar/gky1004] [PMID: 30357411]
[17]
Wang, Y.; Xiao, J.; Suzek, T.O.; Zhang, J.; Wang, J.; Bryant, S.H. PubChem: a public information system for analyzing bioactivities of small molecules. Nucleic Acids Res., 2009, 37, w623-w633.
[http://dx.doi.org/10.1093/nar/gkp456] [PMID: 19498078]
[18]
Hsin, K.Y.; Matsuoka, Y.; Asai, Y.; Kamiyoshi, K.; Watanabe, T.; Kawaoka, Y.; Kitano, H. systemsDock: a web server for network pharmacology-based prediction and analysis. Nucleic Acids Res., 2016, 44(1), 507-513.
[http://dx.doi.org/10.1093/nar/gkw335] [PMID: 27131384]
[19]
Zheng, Q.; Wang, X.J. GOEAST: a web-based software toolkit for Gene Ontology enrichment analysis. Nucleic Acids Res., 2008, 36(Web Server issue), W358-63.,
[http://dx.doi.org/10.1093/nar/gkn276] [PMID: 18487275]
[20]
Huang, W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[21]
Huang, W.; Sherman, B.T.; Lempicki, R.A. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res., 2009, 37(1), 1-13.
[http://dx.doi.org/10.1093/nar/gkn923] [PMID: 19033363]
[22]
Xuemin, G. Traditional Chinese Medicine; China Traditional Chinese Medicine Publishing House: Beijing, 2002, p. 87.
[23]
Zhian, H.; Chengguang, Z.; Xiaoyan, T.; Yanna, B.; Qiuju, Y.; Gaili, M. Effects of ligustrazine on hemorheology in stress rabbits. Chin. J. Misdiagnostics, 2006, 6(13), 2501-2502.
[24]
Deyi, C. Protective effects of Ligustrazine on brain damage in rats. Zhongguo Yaolixue Tongbao, 1999, 151(5), 464.
[25]
Yanmei, S.; Xianli, M.; Chunyu, L.; Zhang, W.; Yi, Z. Effects of volatile oil of Ligusticum Chuanxiong on the survival of rat cerebral cortical neurons in vitro and cerebral ischemia-reperfusion injury. Shizhen Guo Yi Guo Yao Medica Res., 2012, 23(3), 536-539.
[26]
Hong, Z.; Hanhan, H.; Jingze, Z.; Wenyuan, G. Research progress of Chuanxiong-Angelica pairs. Chin. Trad. Patent Med., 2015, 37(1), 184-186.
[27]
Huang, W.; Yao, B.; Sun, L.; Pu, R.; Wang, L.; Zhang, R. Immunohistochemical and in situ hybridization studies of gonadotropin releasing hormone (GnRH) and its receptor in rat digestive tract. Life Sci., 2001, 68(15), 1727-1734.
[http://dx.doi.org/10.1016/S0024-3205(01)00968-7] [PMID: 11270619]
[28]
Chen, H.F.; Jeung, E.B.; Stephenson, M.; Leung, P.C. Human peripheral blood mononuclear cells express gonadotropin-releasing hormone (GnRH), GnRH receptor, and interleukin-2 receptor gamma-chain messenger ribonucleic acids that are regulated by GnRH in vitro. J. Clin. Endocrinol. Metab., 1999, 84(2), 743-750.
[http://dx.doi.org/10.1210/jcem.84.2.5440] [PMID: 10022447]
[29]
Min, W. Research progress on dual regulation of HIF-1alpha after focal cerebral ischemia. Chin. J. Integr. Med., 2018, 16(24), 3636-3638.
[30]
Yang, S.J.; Park, Y.S.; Cho, J.H.; Moon, B.; An, H.J.; Lee, J.Y.; Xie, Z.; Wang, Y.; Pocalyko, D.; Lee, D.C.; Sohn, H.A.; Kang, M.; Kim, J.Y.; Kim, E.; Park, K.C.; Kim, J.A.; Yeom, Y.I. Regulation of hypoxia responses by flavin adenine dinucleotide-dependent modulation of HIF-1 protein stability. EMBO J., 2017, 36(8), 1011-1028.
[http://dx.doi.org/10.15252/embj.201694408] [PMID: 28279976]
[31]
Li, J.K.; Wang, T.; Zhang, H. Rapid noninvasive continuous monitoring of oxygenation in cerebral ischemia and hypoxia. Cardiovasc. Eng., 2010, 10(4), 213-217.
[http://dx.doi.org/10.1007/s10558-010-9116-x] [PMID: 21165773]
[32]
Cheng, C.Y.; Ho, T.Y.; Hsiang, C.Y.; Tang, N.Y.; Hsieh, C.L.; Kao, S.T.; Lee, Y.C. Angelica sinensis exerts angiogenic and anti-apoptotic effects against cerebral ischemia-reperfusion injury by activating p38MAPK/HIF-1[formula: see text]/VEGF-a signaling in rats. Am. J. Chin. Med., 2017, 45(8), 1683-1708.
[http://dx.doi.org/10.1142/S0192415X17500914] [PMID: 29121798]
[33]
Sun, J.J.; Zhang, X.Y.; Qin, X.D.; Zhang, J.; Wang, M.X.; Yang, J.B. MiRNA-210 induces the apoptosis of neuronal cells of rats with cerebral ischemia through activating HIF-1-VEGF pathway. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(6), 2548-2554.
[http://dx.doi.org/10.26355/eurrev_201903_17403] [PMID: 30964182]
[34]
Shah, B.; Püschel, A.W. Regulation of Rap GTPases in mammalian neurons. Biol. Chem., 2016, 397(10), 1055-1069.
[http://dx.doi.org/10.1515/hsz-2016-0165] [PMID: 27186679]
[35]
Matchett, G.A.; Martin, R.D.; Zhang, J.H. Hyperbaric oxygen therapy and cerebral ischemia: neuroprotective mechanisms. Neurol. Res., 2009, 31(2), 114-121.
[http://dx.doi.org/10.1179/174313209X389857] [PMID: 19298750]
[36]
Zhou, F.; Wang, L.; Liu, P.; Hu, W.; Zhu, X.; Shen, H.; Yao, Y. Puerarin protects brain tissue against cerebral ischemia/reperfusion injury by inhibiting the inflammatory response. Neural Regen. Res., 2014, 9(23), 2074-2080.
[http://dx.doi.org/10.4103/1673-5374.147934] [PMID: 25657724]
[37]
Kaixuan, N.; Siyang, L.; Meng, F.; Weili, L.; Xuesong, X. PI3K/Akt/GSK-3beta/beta-catenin signaling pathway promotes nerve cell regeneration and repair. J. Shenyang Med. Coll., 2017, 19(1), 69-71.
[http://dx.doi.org/10.16753/j.cnki.1008-2344.2017.01.022]
[38]
Hong, N. Advances in molecular biology of prolactin and immunity. Med. Immunol., 2002, 25(4), 214-217.
[39]
Strom, J.O.; Theodorsson, A.; Theodorsson, E. Mechanisms of estrogens’ dose-dependent neuroprotective and neurodamaging effects in experimental models of cerebral ischemia. Int. J. Mol. Sci., 2011, 12(3), 1533-1562.
[http://dx.doi.org/10.3390/ijms12031533] [PMID: 21673906]
[40]
Brotfain, E.; Gruenbaum, S.E.; Boyko, M.; Kutz, R.; Zlotnik, A.; Klein, M. Neuroprotection by estrogen and progesterone in traumatic brain injury and spinal cord injury. Curr. Neuropharmacol., 2016, 14(6), 641-653.
[http://dx.doi.org/10.2174/1570159X14666160309123554] [PMID: 26955967]
[41]
Yanmei, S.; Jing, Z.; Xianli, M.; Weizao, L.; Yi, Z. Neuroprotective Effect and mechanism of scutellarin ethyl ester on cerebral ischemia in vitro. Chinese Pharm. J., 2012, 47(15), 1212-1215.
[42]
Bose, S.; Cho, J. Role of chemokine CCL2 and its receptor CCR2 in neurodegenerative diseases. Arch. Pharm. Res., 2013, 36(9), 1039-1050.
[http://dx.doi.org/10.1007/s12272-013-0161-z] [PMID: 23771498]
[43]
Shucheng, H.; Yunman, L.; Weirong, F. Advances in the study of the effects of CCR2/CCL2 on cerebral ischemia-reperfusion injury. Pharmaceut. Clin. Stud., 2018, 26(3), 196-201.
[http://dx.doi.org/10.13664/j.cnki.pcr.2018.03.011]

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