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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

Molecular Mechanisms of Notopterygii rhizoma Et Radix for Treating Arrhythmia Based on Network Pharmacology

Author(s): Penglu Wei, Juju Shang*, Hongxu Liu*, Wenlong Xing and Yupei Tan

Volume 26, Issue 8, 2023

Published on: 23 November, 2022

Page: [1560 - 1570] Pages: 11

DOI: 10.2174/1386207326666221031122803

Price: $65

Abstract

Objective: To explore the possible mechanism for treating NRR in arrhythmia using network pharmacology and molecular docking in this study.

Methods: Active compounds and targets for NRR were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform, SymMap, and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases. Arrhythmia-related genes were acquired from the Comparative Toxicogenomics Database (CTD) and the GeneCards database. Overlapping targets of NRR associated with arrhythmia were acquired and displayed via a Venn diagram. DAVID was applied for GO and KEGG pathway analyses. Cytoscape software and its plug-in were used for PPI network construction, module division and hub nodes screening. Auto- Dock Vina and qRT-PCR were carried out for validation.

Results: In total, 21 active compounds and 57 targets were obtained. Of these, coumarin was the predominant category which contained 15 components and 31 targets. There were 5 key targets for NRR in treating arrhythmia. These targets are involved in the apoptotic process, extrinsic apoptotic signaling pathway in the absence of ligand, and endopeptidase activity involved in the apoptotic process by cytochrome c. The main pathways were the p53 signaling pathway, Hepatitis B and apoptosis. The molecular docking and qRT-PCR displayed good effects on hub node regulation in NRR treatment.

Conclusion: NRR plays an important role in anti-apoptotic mechanisms that modulate the p53 signaling pathway, which may provide insight for future research and clinical applications focusing on arrhythmia therapy.

Graphical Abstract

[1]
Lakkireddy, D.; Vaseghi, M. Sympathetic denervation for treatment of ventricular arrhythmias. J. Atr. Fibrillation, 2020, 13(1), 2404.
[http://dx.doi.org/10.4022/jafib.2404] [PMID: 33024504]
[2]
Markman, T.M.; Nazarian, S. Treatment of ventricular arrhythmias: What’s New? Trends Cardiovasc. Med., 2019, 29(5), 249-261.
[http://dx.doi.org/10.1016/j.tcm.2018.09.014] [PMID: 30268648]
[3]
Dresen, W.F.; Ferguson, J.D. Ventricular arrhythmias. Cardiol. Clin., 2018, 36(1), 129-139.
[http://dx.doi.org/10.1016/j.ccl.2017.08.007] [PMID: 29173673]
[4]
Zhang, R.; Zhu, X.; Bai, H.; Ning, K. Network pharmacology databases for Traditional Chinese Medicine: Review and assessment. Front. Pharmacol., 2019, 10, 123.
[http://dx.doi.org/10.3389/fphar.2019.00123] [PMID: 30846939]
[5]
Wei, M.; Li, H.; Li, Q.; Qiao, Y.; Ma, Q.; Xie, R.; Wang, R.; Liu, Y.; Wei, C.; Li, B.; Zheng, C.; Sun, B.; Yu, B. Based on network pharmacology to explore the molecular targets and mechanisms of gegen qinlian decoction for the treatment of ulcerative colitis. BioMed Res. Int., 2020, 2020, 1-18.
[http://dx.doi.org/10.1155/2020/5217405] [PMID: 33299870]
[6]
Xu, J.; Wang, F.; Guo, J.; Xu, C.; Cao, Y.; Fang, Z.; Wang, Q. Pharmacological mechanisms underlying the neuroprotective effects of Alpinia oxyphylla Miq. on Alzheimer’s disease. Int. J. Mol. Sci., 2020, 21(6), 2071.
[http://dx.doi.org/10.3390/ijms21062071] [PMID: 32197305]
[7]
Chinese Pharmacopoeia Commission. In: Pharmacopoeia of the People’s Republic of China; China Medical Science and Technology Press: Beijing, 2015; pp. 182-183.
[8]
Hong, L.; Juanjuan, Z.; Xiaoxiang, Z.; Wei, W. Therapeutical effect of Radix aconiti and Astragalus extracts on models of experimental bradycardia animal. Pak. J. Pharm. Sci., 2014, 27(3), 439-444.
[http://dx.doi.org/10.1016/j.drudis.2014.01.001] [PMID: 24811798]
[9]
Guo, P.; Lang, Y.J.; Zhang, G.T. Research progress on chemical constituents and pharmacological activities of Notopterygii Rhizoma et Radix. Zhongchengyao, 2019, 41(10), 2445-2459.
[http://dx.doi.org/10.3969/j.issn.1001-1528.2019.10.033]
[10]
Gong, Z.H.; Duan, Y.Q.; Fu, X.Y.; Ma, J.; Wang, L.Y.; Bai, M. Study on pharmacological mechanisms of Notopterygii Rhizoma et Radix. Asia-Pacific Tradit Med., 2019, 15(5), 192-194.
[http://dx.doi.org/10.11954/ytctyy.201905061]
[11]
Ma, L.M.; Yang, J.L. Research progress on chemical constituents and pharmacological activities of Notopterygii Rhizoma et Radix. Chin. Tradit. Herbal Drugs, 2021, 52(19), 6111-6120.
[http://dx.doi.org/10.7501/j.issn.0253-2670.2021.19.034]
[12]
Sinatra, L.; Bandolik, J.J.; Roatsch, M.; Sönnichsen, M.; Schoeder, C.T.; Hamacher, A.; Schöler, A.; Borkhardt, A.; Meiler, J.; Bhatia, S.; Kassack, M.U.; Hansen, F.K. Hydroxamic Acids Immobilized on Resins (HAIRs): Synthesis of dual‐targeting HDAC inhibitors and HDAC degraders (PROTACs). Angew. Chem. Int. Ed., 2020, 59(50), 22494-22499.
[http://dx.doi.org/10.1002/anie.202006725] [PMID: 32780485]
[13]
Wong, D.P.; Roy, N.K.; Zhang, K.; Anukanth, A.; Asthana, A.; Shirkey-Son, N.J.; Dunmire, S.; Jones, B.J.; Lahr, W.S.; Webber, B.R.; Moriarity, B.S.; Caimi, P.; Parameswaran, R. A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers. Nat. Commun., 2022, 13(1), 217.
[http://dx.doi.org/10.1038/s41467-021-27853-w] [PMID: 35017485]
[14]
Batool, M.; Ahmad, B.; Choi, S. A structure-based drug discovery paradigm. Int. J. Mol. Sci., 2019, 20(11), 2783.
[http://dx.doi.org/10.3390/ijms20112783] [PMID: 31174387]
[15]
Parker, C.G.; Galmozzi, A.; Wang, Y.; Correia, B.E.; Sasaki, K.; Joslyn, C.M.; Kim, A.S.; Cavallaro, C.L.; Lawrence, R.M.; Johnson, S.R.; Narvaiza, I.; Saez, E.; Cravatt, B.F. Ligand and target discovery by fragment-based screening in human cells. Cell, 2017, 168(3), 527-541.e29.
[http://dx.doi.org/10.1016/j.cell.2016.12.029] [PMID: 28111073]
[16]
Xie, T.; Song, S.; Li, S.; Ouyang, L.; Xia, L.; Huang, J. Review of natural product databases. Cell Prolif., 2015, 48(4), 398-404.
[http://dx.doi.org/10.1111/cpr.12190] [PMID: 26009974]
[17]
Yu, W.; MacKerell, A.D. Jr Computer-aided drug design methods. Methods Mol. Biol., 2017, 1520, 85-106.
[http://dx.doi.org/10.1007/978-1-4939-6634-9_5] [PMID: 27873247]
[18]
Zhong, F.; Xing, J.; Li, X.; Liu, X.; Fu, Z.; Xiong, Z.; Lu, D.; Wu, X.; Zhao, J.; Tan, X.; Li, F.; Luo, X.; Li, Z.; Chen, K.; Zheng, M.; Jiang, H. Artificial intelligence in drug design. Sci. China Life Sci., 2018, 61(10), 1191-1204.
[http://dx.doi.org/10.1007/s11427-018-9342-2] [PMID: 30054833]
[19]
Huang, K.; Zhang, P.; Zhang, Z.; Youn, J.Y.; Wang, C.; Zhang, H.; Cai, H. Traditional Chinese Medicine (TCM) in the treatment of COVID-19 and other viral infections: Efficacies and mechanisms. Pharmacol. Ther., 2021, 225, 107843.
[http://dx.doi.org/10.1016/j.pharmthera.2021.107843] [PMID: 33811957]
[20]
Mo, S.L.; Liu, W.F.; Chen, Y.; Luo, H.B.; Sun, L.B.; Chen, X.W.; Zhou, Z.W.; Sneed, K.B.; Li, C.G.; Du, Y.M.; Liang, J.; Zhou, S.F. Ligand- and protein-based modeling studies of the inhibitors of human cytochrome P450 2D6 and a virtual screening for potential inhibitors from the Chinese herbal medicine, Scutellaria baicalensis (Huangqin, Baikal Skullcap). Comb. Chem. High Throughput Screen., 2012, 15(1), 36-80.
[http://dx.doi.org/10.2174/138620712798280826] [PMID: 21846324]
[21]
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]
[22]
Wu, Y.; Zhang, F.; Yang, K.; Fang, S.; Bu, D.; Li, H.; Sun, L.; Hu, H.; Gao, K.; Wang, W.; Zhou, X.; Zhao, Y.; Chen, J. SymMap: An integrative database of traditional Chinese medicine enhanced by symptom mapping. Nucleic Acids Res., 2019, 47(D1), D1110-D1117.
[http://dx.doi.org/10.1093/nar/gky1021] [PMID: 30380087]
[23]
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]
[24]
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]
[25]
Stelzer, G.; Rosen, N.; Plaschkes, I. The genecards suite: From gene data mining to disease genome sequence analyses. Curr. Protoc. Bioinform., 2016, 54(1), 1.30.1-1.30.33.
[http://dx.doi.org/10.1002/cpbi.5]
[26]
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]
[27]
Huang, D.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]
[28]
Huang, D.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]
[29]
Wu, X.W.; Zhang, Y.B.; Zhang, L.; Yang, X.W. Simultaneous quantification of 33 active components in Notopterygii Rhizoma et Radix using ultra high performance liquid chromatography with tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2018, 1092, 244-251.
[http://dx.doi.org/10.1016/j.jchromb.2018.06.006] [PMID: 29913336]
[30]
Ma, Y.L.; Lin, J.M.; Ma, L.; Zhang, C. Progress in researches on notopterygium. Anhui Nongye Kexue, 2010, 38(24), 13092-13093.
[http://dx.doi.org/10.13989/j.cnki.0517-6611.2010.24.095]
[31]
Cheng, Y.Z.; Shan, Z.Y.; Chen, Y.P. Comparison of antiarrhythmic effects of different components of Qianghuishui solution. J. Basic Clin. Med., 1998, 4(2), 43.
[32]
Mohammadi, A.; Balizadeh Karami, A.R.; Dehghan Mashtani, V.; Sahraei, T.; Bandani Tarashoki, Z.; Khattavian, E.; Mobarak, S.; Moradi Kazerouni, H.; Radmanesh, E. Evaluation of oxidative stress, apoptosis, and expression of MicroRNA-208a and MicroRNA-1 in cardiovascular patients. Rep. Biochem. Mol. Biol., 2021, 10(2), 183-196.
[http://dx.doi.org/10.52547/rbmb.10.2.183] [PMID: 34604408]
[33]
Luo, Z.; Yan, C.; Yu, P.; Bao, W.; Shen, X.; Zheng, W.; Lin, X.; Wang, Z.; Chen, H.; Chen, F.; Liu, D.; Huang, M. CASP3 genetic variants and susceptibility to atrial fibrillation in Chinese Han population. Int. J. Cardiol., 2015, 183, 1-5.
[http://dx.doi.org/10.1016/j.ijcard.2015.01.048] [PMID: 25662045]
[34]
Li, Y.; Song, B.; Xu, C. Effects of Guanfu total base on Bcl-2 and Bax expression and correlation with atrial fibrillation. Hellenic J. Cardiol., 2018, 59(5), 274-278.
[http://dx.doi.org/10.1016/j.hjc.2018.02.009] [PMID: 29501704]
[35]
Diao, S.L.; Xu, H.P.; Zhang, B.; Ma, B.X.; Liu, X.L. Associations of MMP-2, BAX, and Bcl-2 mRNA and protein expressions with development of atrial fibrillation. Med. Sci. Monit., 2016, 22, 1497-1507.
[http://dx.doi.org/10.12659/MSM.895715] [PMID: 27141955]
[36]
Xu, G.J.; Gan, T.Y.; Tang, B.P.; Chen, Z.H.; Mahemuti, A.; Jiang, T.; Song, J.G.; Guo, X.; Li, Y.D.; Miao, H.J.; Zhou, X.H.; Zhang, Y.; Li, J.X. Accelerated fibrosis and apoptosis with ageing and in atrial fibrillation: Adaptive responses with maladaptive consequences. Exp. Ther. Med., 2013, 5(3), 723-729.
[http://dx.doi.org/10.3892/etm.2013.899] [PMID: 23403858]
[37]
Zhan, C.; Liu, G.; Li, J.; Li, G.; Li, T.; Zhao, H.; Li, L.; Yang, W.; Bai, N.; Zheng, M.; Yang, J.; Li, W. Rotenone and 3-bromopyruvate toxicity impacts electrical and structural cardiac remodeling in rats. Toxicol. Lett., 2020, 318, 57-64.
[http://dx.doi.org/10.1016/j.toxlet.2019.09.024] [PMID: 31585160]
[38]
Zhang, J.; Zhang, X. Ischaemic preconditioning‐induced serum exosomes protect against myocardial ischaemia/reperfusion injury in rats by activating the PI3K/AKT signalling pathway. Cell Biochem. Funct., 2021, 39(2), 287-295.
[http://dx.doi.org/10.1002/cbf.3578] [PMID: 32767595]
[39]
Zheng, N.; Li, H.; Wang, X.; Zhao, Z.; Shan, D. Oxidative stress-induced cardiomyocyte apoptosis is associated with dysregulated Akt/p53 signaling pathway. J. Recept. Signal Transduct. Res., 2020, 40(6), 599-604.
[http://dx.doi.org/10.1080/10799893.2020.1772297] [PMID: 32460597]
[40]
Xu, D.; Murakoshi, N.; Igarashi, M.; Hirayama, A.; Ito, Y.; Seo, Y.; Tada, H.; Aonuma, K. PPAR-γ activator pioglitazone prevents age-related atrial fibrillation susceptibility by improving antioxidant capacity and reducing apoptosis in a rat model. J. Cardiovasc. Electrophysiol., 2012, 23(2), 209-217.
[http://dx.doi.org/10.1111/j.1540-8167.2011.02186.x] [PMID: 21954843]
[41]
Ayoub, I.M.; Radhakrishnan, J.; Gazmuri, R.J. Targeting mitochondria for resuscitation from cardiac arrest. Crit. Care Med., 2008, 36(11), S440-S446.
[http://dx.doi.org/10.1097/CCM.0b013e31818a89f4] [PMID: 20449908]
[42]
Wei, P.L.; Qi, Y.F.; Tan, Y.P.; Long, D.H.; Xing, W.L. Molecular mechanisms of Notopterygii Rhizoma Et radix for the treatment of arrhythmia based on network pharmacology; Res. Sqare, 2021.
[http://dx.doi.org/10.21203/rs.3.rs-1047765/v1]

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