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Current Computer-Aided Drug Design

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ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

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Research Article

Exploration of the Mechanism of Tripterygium Wilfordii in the Treatment of Myocardial Fibrosis Based on Network Pharmacology and Molecular Docking

Author(s): Yang Ming, Liu Jiachen, Guo Tao and Wang Zhihui*

Volume 19, Issue 1, 2023

Published on: 16 December, 2022

Page: [68 - 79] Pages: 12

DOI: 10.2174/1573409919666221028120329

open access plus

Abstract

Background: A network pharmacology study on the biological action of Tripterygium wilfordii on myocardial fibrosis (MF).

Methods: The effective components and potential targets of tripterygium wilfordii were screened from the TCMSP database to develop a combination target network. A protein-protein interaction network was constructed by analyzing the interaction between tripterygium wilfordii and MF; then, the Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed. Furthermore, molecular docking was utilized to verify the network analysis results.

Results: It was predicted that MF has 29 components contributing to its effectiveness and 87 potential targets. It is predicted that Tripterygium wilfordii has 29 active components and 87 potential targets for the treatment of MF. The principal active components of tripterygium wilfordii include kaempferol, β-sitosterol, triptolide, and Nobiletin. Signaling pathways: AGE-RAGE, PI3K-Akt, and MAPK may be involved in the mechanism of its action.7 Seven key targets (TNF, STAT3, AKT1, TP53, VEGFA, CASP3, STAT1) are possibly involved in treating MF by tripterygium wilfordii.

Conclusion: This study shows the complex network relationship between multiple components, targets, and pathways of Tripterygium wilfordii in treating MF.

Keywords: Tripterygium wilfordii, myocardial fibrosis, network pharmacology, molecular docking, CAD, GO.

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[1]
López, B.; Ravassa, S.; Moreno, M.U.; José, G.S.; Beaumont, J.; González, A.; Díez, J. Diffuse myocardial fibrosis: Mechanisms, diagnosis and therapeutic approaches. Nat. Rev. Cardiol., 2021, 18(7), 479-498.
[http://dx.doi.org/10.1038/s41569-020-00504-1] [PMID: 33568808]
[2]
Hinderer, S.; Schenke-Layland, K. Cardiac fibrosis – A short review of causes and therapeutic strategies. Adv. Drug Deliv. Rev., 2019, 146, 77-82.
[http://dx.doi.org/10.1016/j.addr.2019.05.011] [PMID: 31158407]
[3]
Li, Y.; Zhu, W.; He, H.; Garov, Y.A.; Bai, L.; Zhang, L.; Wang, J.; Wang, J.; Zhou, X. Efficacy and safety of Tripterygium Wilfordii Hook. F for connective tissue disease-associated interstitial lung disease: A systematic review and meta-analysis. Front. Pharmacol., 2021, 12, 691031.
[http://dx.doi.org/10.3389/fphar.2021.691031] [PMID: 34177599]
[4]
Huang, W.; Liu, W.; Xiao, Y.; Zheng, H.; Xiao, Y.; Jia, Q.; Jiang, H.; Zhu, Z.; Xia, C.; Han, X.; Sun, R.; Nan, H.; Feng, Z.; Wang, S.; Zhao, J. Tripterygium and its extracts for diabetic nephropathy: Efficacy and pharmacological mechanisms. Biomed. Pharmacother., 2020, 121, 109599.
[http://dx.doi.org/10.1016/j.biopha.2019.109599] [PMID: 31707345]
[5]
Liu, Y.; Gao, L.; Guo, S.; Liu, Y.; Zhao, X.; Li, R.; Yan, X.; Li, Y.; Wang, S.; Niu, X.; Yao, L.; Zhang, Y.; Li, L.; Yang, H. Kaempferol alleviates angiotensin II-Induced cardiac dysfunction and interstitial fibrosis in mice. Cell. Physiol. Biochem., 2017, 43(6), 2253-2263.
[http://dx.doi.org/10.1159/000484304] [PMID: 29073623]
[6]
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]
[7]
Chen, L.; Zhang, Y.H.; Wang, S.; Zhang, Y.; Huang, T.; Cai, Y.D. Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways. PLoS One, 2017, 12(9), e0184129.
[http://dx.doi.org/10.1371/journal.pone.0184129] [PMID: 28873455]
[8]
Xu, S.; Feng, Y.; He, W.; Xu, W.; Xu, W.; Yang, H.; Li, X. Celastrol in metabolic diseases: Progress and application prospects. Pharmacol. Res., 2021, 167, 105572.
[http://dx.doi.org/10.1016/j.phrs.2021.105572] [PMID: 33753246]
[9]
Hsin, K.Y.; Ghosh, S.; Kitano, H. Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology. PLoS One, 2013, 8(12), e83922.
[http://dx.doi.org/10.1371/journal.pone.0083922] [PMID: 24391846]
[10]
Babu, S.; Jayaraman, S. An update on β-sitosterol: A potential herbal nutraceutical for diabetic management. Biomed. Pharmacother., 2020, 131, 110702.
[http://dx.doi.org/10.1016/j.biopha.2020.110702] [PMID: 32882583]
[11]
Yin, Y.; Liu, X.; Liu, J.; Cai, E.; Zhu, H.; Li, H.; Zhang, L.; Li, P.; Zhao, Y. Beta-sitosterol and its derivatives repress lipopolysaccharide/d-galactosamine-induced acute hepatic injury by inhibiting the oxidation and inflammation in mice. Bioorg. Med. Chem. Lett., 2018, 28(9), 1525-1533.
[http://dx.doi.org/10.1016/j.bmcl.2018.03.073] [PMID: 29622518]
[12]
Shen, J.; Ma, H.; Wang, C. Triptolide improves myocardial fibrosis in rats through inhibition of nuclear factor kappa B and NLR family pyrin domain containing 3 inflammasome pathway. Korean J. Physiol. Pharmacol., 2021, 25(6), 533-543.
[http://dx.doi.org/10.4196/kjpp.2021.25.6.533] [PMID: 34697264]
[13]
Zhou, Y.; Yin, T.; Shi, M.; Chen, M.; Wu, X.; Wang, K.; Cheang, I.; Li, Y.; Shang, H.; Zhang, H.; Li, X. Nobiletin attenuates pathological cardiac remodeling after myocardial infarction via Activating PPARγ and PGC1α. PPAR Res., 2021, 2021, 1-17.
[http://dx.doi.org/10.1155/2021/9947656] [PMID: 34422028]
[14]
Ntusi, N.A.B.; Francis, J.M.; Sever, E.; Liu, A.; Piechnik, S.K.; Ferreira, V.M.; Matthews, P.M.; Robson, M.D.; Wordsworth, P.B.; Neubauer, S.; Karamitsos, T.D. Anti-TNF modulation reduces myocardial inflammation and improves cardiovascular function in systemic rheumatic diseases. Int. J. Cardiol., 2018, 270, 253-259.
[http://dx.doi.org/10.1016/j.ijcard.2018.06.099] [PMID: 30017519]
[15]
Zhao, K.; Li, Y.; Zhou, Z.; Mao, Y.; Wu, X.; Hua, D.; Yong, Y.; Li, P. Ginkgolide A alleviates cardiac remodeling in mice with myocardial infarction via binding to matrix metalloproteinase-9 to attenuate inflammation. Eur. J. Pharmacol., 2022, 923, 174932.
[http://dx.doi.org/10.1016/j.ejphar.2022.174932] [PMID: 35367419]
[16]
Lin, C.F.; Su, C.J.; Liu, J.H.; Chen, S.T.; Huang, H.L.; Pan, S.L. Potential effects of CXCL9 and CCL20 on cardiac fibrosis in patients with myocardial infarction and isoproterenol-treated rats. J. Clin. Med., 2019, 8(5), 659.
[http://dx.doi.org/10.3390/jcm8050659] [PMID: 31083544]
[17]
Singh, A.K.; Kashyap, M.P.; Tripathi, V.K.; Singh, S.; Garg, G.; Rizvi, S.I. Neuroprotection through rapamycin-induced activation of autophagy and PI3K/Akt1/mTOR/CREB signaling against amyloid-β-induced oxidative stress, synaptic/neurotransmission dysfunction, and neurodegeneration in adult rats. Mol. Neurobiol., 2017, 54(8), 5815-5828.
[http://dx.doi.org/10.1007/s12035-016-0129-3] [PMID: 27660271]
[18]
Zhong, S.; Guo, H.; Wang, H.; Xing, D.; Lu, T.; Yang, J.; Wang, C. Apelin-13 alleviated cardiac fibrosis via inhibiting the PI3K/Akt pathway to attenuate oxidative stress in rats with myocardial infarction-induced heart failure. Biosci. Rep., 2020, 40(4), BSR20200040.
[http://dx.doi.org/10.1042/BSR20200040] [PMID: 32207519]
[19]
Kim, D.; Lee, I.H.; Kim, S.; Choi, M.; Kim, H.; Ahn, S.; Saw, P.E.; Jeon, H.; Lee, Y.; Jon, S. A specific STAT3-binding peptide exerts antiproliferative effects and antitumor activity by inhibiting STAT3 phosphorylation and signaling. Cancer Res., 2014, 74(8), 2144-2151.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-2187] [PMID: 24576829]
[20]
Zhuang, L.; Jia, K.; Chen, C.; Li, Z.; Zhao, J.; Hu, J.; Zhang, H.; Fan, Q.; Huang, C.; Xie, H.; Lu, L.; Shen, W.; Ning, G.; Wang, J.; Zhang, R.; Chen, K.; Yan, X. DYRK1B-STAT3 drives cardiac hypertrophy and heart failure by impairing mitochondrial bioenergetics. Circulation, 2022, 145(11), 829-846.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055727] [PMID: 35235343]
[21]
Mak, T.W.; Hauck, L.; Grothe, D.; Billia, F. p53 regulates the cardiac transcriptome. Proc. Natl. Acad. Sci. USA, 2017, 114(9), 2331-2336.
[http://dx.doi.org/10.1073/pnas.1621436114] [PMID: 28193895]
[22]
Haywood, M.E.; Cocciolo, A.; Porter, K.F.; Dobrinskikh, E.; Slavov, D.; Graw, S.L.; Reece, T.B.; Ambardekar, A.V.; Bristow, M.R.; Mestroni, L.; Taylor, M.R.G. Transcriptome signature of ventricular arrhythmia in dilated cardiomyopathy reveals increased fibrosis and activated TP53. J. Mol. Cell. Cardiol., 2020, 139, 124-134.
[http://dx.doi.org/10.1016/j.yjmcc.2019.12.010] [PMID: 31958463]
[23]
Du, Y.; Ge, Y.; Xu, Z.; Aa, N.; Gu, X.; Meng, H.; Lin, Z.; Zhu, D.; Shi, J.; Zhuang, R.; Wu, X.; Wang, X.; Yang, Z. Hypoxia-inducible factor 1 alpha (HIF-1α;)/Vascular Endothelial Growth Factor (VEGF) pathway participates in angiogenesis of myocardial infarction in muscone-treated mice: Preliminary study. Med. Sci. Monit., 2018, 24, 8870-8877.
[http://dx.doi.org/10.12659/MSM.912051] [PMID: 30531686]
[24]
Bernard, A.; Chevrier, S.; Beltjens, F.; Dosset, M.; Viltard, E.; Lagrange, A.; Derangère, V.; Oudot, A.; Ghiringhelli, F.; Collin, B.; Apetoh, L.; Feron, O.; Chen, S.; Arnould, L.; Végran, F.; Boidot, R. Cleaved caspase-3 transcriptionally regulates angiogenesis-promoting chemotherapy resistance. Cancer Res., 2019, 79(23), 5958-5970.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-0840] [PMID: 31611309]
[25]
Liu, W.; Feng, Y.; Wang, X.; Ding, J.; Li, H.; Guan, H.; Chen, Z. Human umbilical vein endothelial cells-derived exosomes enhance cardiac function after acute myocardial infarction by activating the PI3K/AKT signaling pathway. Bioengineered, 2022, 13(4), 8850-8865.
[http://dx.doi.org/10.1080/21655979.2022.2056317] [PMID: 35361041]
[26]
Zhao, J.; Randive, R.; Stewart, J.A. Molecular mechanisms of AGE/RAGE-mediated fibrosis in the diabetic heart. World J. Diabetes, 2014, 5(6), 860-867.
[http://dx.doi.org/10.4239/wjd.v5.i6.860] [PMID: 25512788]
[27]
Lee, T.W.; Kao, Y.H.; Chen, Y.J.; Chao, T.F.; Lee, T.I. Therapeutic potential of vitamin D in AGE/RAGE-related cardiovascular diseases. Cell. Mol. Life Sci., 2019, 76(20), 4103-4115.
[http://dx.doi.org/10.1007/s00018-019-03204-3] [PMID: 31250032]
[28]
Zhang, Q.; Wang, L.; Wang, S.; Cheng, H.; Xu, L.; Pei, G.; Wang, Y.; Fu, C.; Jiang, Y.; He, C.; Wei, Q. Signaling pathways and targeted therapy for myocardial infarction. Signal Transduct. Target. Ther., 2022, 7(1), 78.
[http://dx.doi.org/10.1038/s41392-022-00925-z] [PMID: 35273164]
[29]
Kazakov, A.; Hall, R.; Jagoda, P.; Bachelier, K.; Müller-Best, P.; Semenov, A.; Lammert, F.; Böhm, M.; Laufs, U. Inhibition of endothelial nitric oxide synthase induces and enhances myocardial fibrosis. Cardiovasc. Res., 2013, 100(2), 211-221.
[http://dx.doi.org/10.1093/cvr/cvt181] [PMID: 23863197]
[30]
Li, J.; Zhang, Y.; Li, C.; Xie, J.; Liu, Y.; Zhu, W.; Zhang, X.; Jiang, S.; Liu, L.; Ding, Z. HSPA12B attenuates cardiac dysfunction and remodelling after myocardial infarction through an eNOS-dependent mechanism. Cardiovasc. Res., 2013, 99(4), 674-684.
[http://dx.doi.org/10.1093/cvr/cvt139] [PMID: 23729663]
[31]
Hayakawa, K.; Takemura, G.; Kanoh, M.; Li, Y.; Koda, M.; Kawase, Y.; Maruyama, R.; Okada, H.; Minatoguchi, S.; Fujiwara, T.; Fujiwara, H. Inhibition of granulation tissue cell apoptosis during the subacute stage of myocardial infarction improves cardiac remodeling and dysfunction at the chronic stage. Circulation, 2003, 108(1), 104-109.
[http://dx.doi.org/10.1161/01.CIR.0000074225.62168.68] [PMID: 12821555]

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