Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Molecular Mechanism of Qingzaojiufei Decoction in the Treatment of Pulmonary Fibrosis based on Network Pharmacology and Molecular Docking

Author(s): Yilong Zhao, Bohao Liu, Yixing Li, Zhe Chen, Xingzhuo Zhu, Runyi Tao, Zhiyu Wang, Hongyi Wang, Yanpeng Zhang, Shuguang Yan*, Qiuyu Gong* and Guangjian Zhang*

Volume 29, Issue 27, 2023

Published on: 13 September, 2023

Page: [2161 - 2176] Pages: 16

DOI: 10.2174/1381612829666230911105931

Price: $65

Abstract

Background: In recent years, pulmonary fibrosis (PF) has increased in incidence and prevalence. Qingzaojiufei decoction (QD) is a herbal formula that is used for the treatment of PF.

Objective: In this research, network pharmacology and molecular docking methods were used to explore the major chemical components and potential mechanisms of QD in the treatment of PF.

Methods: The principal components and corresponding protein targets of QD were used to screen on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) and high-throughput experiment-and reference-guided database (HERB), Cytoscape 3.7.2 was used to construct the drug-component-target network. PF targets were collected by GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The protein-protein interaction (PPI) network was constructed by importing compound-disease intersection targets into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized by Cytoscape3.7.2. We further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the intersecting targets. In the last, we validated the core targets and active compounds by molecular docking.

Results: The key compounds of quercetin, (-)-epigallocatechin-3-gallate, and kaempferol of QD were obtained. The key targets of AKT1, TNF, and IL6 of QD were obtained. The molecular docking results show that quercetin, (-)-epigallocatechin-3-gallate and kaempferol work well with AKT1, TNF and IL6.

Conclusion: This research shows the multiple active components and molecular mechanism of QD in the treatment of PF and offers resources and suggestions for future studies.

« Previous Next »
[1]
Richeldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis. Lancet 2017; 389(10082): 1941-52.
[http://dx.doi.org/10.1016/S0140-6736(17)30866-8] [PMID: 28365056]
[2]
Wu Q, Zhang K, Jiang S, et al. p53: A key protein that regulates pulmonary fibrosis. Oxid Med Cell Longev 2020; 2020: 1-13.
[http://dx.doi.org/10.1155/2020/6635794] [PMID: 33312337]
[3]
Spagnolo P, Kropski JA, Jones MG, et al. Idiopathic pulmonary fibrosis: Disease mechanisms and drug development. Pharmacol Ther 2021; 222: 107798.
[http://dx.doi.org/10.1016/j.pharmthera.2020.107798] [PMID: 33359599]
[4]
Martinez FJ, Collard HR, Pardo A, et al. Idiopathic pulmonary fibrosis. Nat Rev Dis Primers 2017; 3(1): 17074.
[http://dx.doi.org/10.1038/nrdp.2017.74] [PMID: 29052582]
[5]
Meyer KC. Pulmonary fibrosis, part I: Epidemiology, pathogenesis, and diagnosis. Expert Rev Respir Med 2017; 11(5): 1-17.
[http://dx.doi.org/10.1080/17476348.2017.1312346] [PMID: 28345383]
[6]
Lederer DJ, Martinez FJ. Idiopathic pulmonary fibrosis. N Engl J Med 2018; 378(19): 1811-23.
[http://dx.doi.org/10.1056/NEJMra1705751] [PMID: 29742380]
[7]
Wenhui YSW. Historical evolution and modern application process of classical prescription Qingzao jiufei tang. China Pharm 2022; 33(16): 2044-8.
[8]
Shijun CLHMYGW. Anti-inflammatory effect of qingzaojiufei decoction on lung injury induced by SiO2 in rats. Occup Health Emerg Rescue 2020; 38(05): 437-42.
[9]
WANG LGY. Runshao T. Based on the theory of collateral disease to verify the efficacy of modified qingzao jiufei decoction in the treatment of idiopathic pulmonary fibrosis and analysis of serum inflammatory factor levels. Clinic J of Tradi Chinese Med 2022; 34(12): 2355-9.
[10]
Dehong SWX. The protective effect of qingzaojiufei soup on radiation-induced pulmonary injury and its impact on cell growth factor-CTGF,PDGF. Zhongguo Shiyan Fangjixue Zazhi 2009; 15(11): 95-8.
[11]
Nogales C, Mamdouh ZM, List M, Kiel C, Casas AI, Schmidt HHHW. Network pharmacology: Curing causal mechanisms instead of treating symptoms. Trends Pharmacol Sci 2022; 43(2): 136-50.
[http://dx.doi.org/10.1016/j.tips.2021.11.004] [PMID: 34895945]
[12]
Ru J, Li P, Wang J, et al. 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]
[13]
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): D1089-95.
[PMID: 23203875]
[14]
Fang S, Dong L, Liu L, et al. HERB: A high-throughput experiment- and reference-guided database of traditional Chinese medicine. Nucleic Acids Res 2021; 49(D1): D1197-206.
[http://dx.doi.org/10.1093/nar/gkaa1063] [PMID: 33264402]
[15]
Wang J, Hou T. Advances in computationally modeling human oral bioavailability. Adv Drug Deliv Rev 2015; 86: 11-6.
[http://dx.doi.org/10.1016/j.addr.2015.01.001] [PMID: 25582307]
[16]
Zhang J, Zhou Y, Ma Z. Multi-target mechanism of Tripteryguim wilfordii Hook for treatment of ankylosing spondylitis based on network pharmacology and molecular docking. Ann Med 2021; 53(1): 1091-9.
[http://dx.doi.org/10.1080/07853890.2021.1918345] [PMID: 34259096]
[17]
Si H, Chen Y, Ma K, Duan Y, Zhai H. Network pharmacology integrated molecular docking to reveal the autism and mechanism of baohewan heshiwei wen dan tang. Curr Pharm Des 2022; 28(39): 3231-41.
[http://dx.doi.org/10.2174/1381612828666220926095922] [PMID: 36165527]
[18]
Bateman A, Martin M-J, Orchard S, et al. UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Res 2021; 49(D1): D480-9.
[http://dx.doi.org/10.1093/nar/gkaa1100] [PMID: 33237286]
[19]
Safran M, Dalah I, Alexander J, et al. GeneCards version 3: The human gene integrator. Database 2010; 2010(0): baq020.
[http://dx.doi.org/10.1093/database/baq020] [PMID: 20689021]
[20]
Amberger JS, Bocchini CA, Schiettecatte F, Scott AF, Hamosh A. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res 2015; 43(D1): D789-98.
[http://dx.doi.org/10.1093/nar/gku1205] [PMID: 25428349]
[21]
Szklarczyk D, Morris JH, Cook H, et al. The STRING database in 2017: Quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res 2017; 45(D1): D362-8.
[http://dx.doi.org/10.1093/nar/gkw937] [PMID: 27924014]
[22]
Zhou Y, Zhou B, Pache L, et al. 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]
[23]
Gaudet P, Logie C, Lovering RC, Kuiper M, Lægreid A, Thomas PD. Gene Ontology representation for transcription factor functions. Biochim Biophys Acta Gene Regul Mech 2021; 1864(11-12): 194752.
[http://dx.doi.org/10.1016/j.bbagrm.2021.194752] [PMID: 34461313]
[24]
Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. KEGG: New perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 2017; 45(D1): D353-61.
[http://dx.doi.org/10.1093/nar/gkw1092] [PMID: 27899662]
[25]
Ferreira L, dos Santos R, Oliva G, Andricopulo A. Molecular docking and structure-based drug design strategies. Molecules 2015; 20(7): 13384-421.
[http://dx.doi.org/10.3390/molecules200713384] [PMID: 26205061]
[26]
Berman HM, Westbrook J, Feng Z, et al. The protein data bank. Nucleic Acids Res 2000; 28(1): 235-42.
[http://dx.doi.org/10.1093/nar/28.1.235] [PMID: 10592235]
[27]
Li X, Wei S, Niu S, et al. Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of huanglian jiedu decoction against sepsis. Comput Biol Med 2022; 144: 105389.
[http://dx.doi.org/10.1016/j.compbiomed.2022.105389] [PMID: 35303581]
[28]
Kim S, Chen J, Cheng T, et al. PubChem 2019 update: Improved access to chemical data. Nucleic Acids Res 2019; 47(D1): D1102-9.
[http://dx.doi.org/10.1093/nar/gky1033] [PMID: 30371825]
[29]
Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles’ heel of senescent cells: From transcriptome to senolytic drugs. Aging Cell 2015; 14(4): 644-58.
[http://dx.doi.org/10.1111/acel.12344] [PMID: 25754370]
[30]
Hohmann MS, Habiel DM, Coelho AL, Verri WA Jr, Hogaboam CM. Quercetin enhances ligand-induced apoptosis in senescent idiopathic pulmonary fibrosis fibroblasts and reduces lung fibrosis in vivo. Am J Respir Cell Mol Biol 2019; 60(1): 28-40.
[http://dx.doi.org/10.1165/rcmb.2017-0289OC] [PMID: 30109946]
[31]
Sriram N, Kalayarasan S, Sudhandiran G. Epigallocatechin-3-gallate augments antioxidant activities and inhibits inflammation during bleomycin-induced experimental pulmonary fibrosis through Nrf2-Keap1 signaling. Pulm Pharmacol Ther 2009; 22(3): 221-36.
[http://dx.doi.org/10.1016/j.pupt.2008.12.010] [PMID: 19138753]
[32]
Gong JH, Cho IH, Shin D, Han SY, Park SH, Kang YH. Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice. Lab Invest 2014; 94(3): 297-308.
[http://dx.doi.org/10.1038/labinvest.2013.137] [PMID: 24378645]
[33]
Kim HS, Moon SJ, Lee SE, Hwang GW, Yoo HJ, Song JW. The arachidonic acid metabolite 11,12-epoxyeicosatrienoic acid alleviates pulmonary fibrosis. Exp Mol Med 2021; 53(5): 864-74.
[http://dx.doi.org/10.1038/s12276-021-00618-7] [PMID: 33990688]
[34]
Du G, Jin L, Han X, Song Z, Zhang H, Liang W. Naringenin: A potential immunomodulator for inhibiting lung fibrosis and metastasis. Cancer Res 2009; 69(7): 3205-12.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-3393] [PMID: 19318568]
[35]
Larson-Casey JL, Deshane JS, Ryan AJ, Thannickal VJ, Carter AB. Macrophage akt1 kinase-mediated mitophagy modulates apoptosis resistance and pulmonary fibrosis. Immunity 2016; 44(3): 582-96.
[http://dx.doi.org/10.1016/j.immuni.2016.01.001] [PMID: 26921108]
[36]
Abdalla M, Sabbineni H, Prakash R, Ergul A, Fagan SC, Somanath PR. The Akt inhibitor, triciribine, ameliorates chronic hypoxia-induced vascular pruning and TGFβ-induced pulmonary fibrosis. Br J Pharmacol 2015; 172(16): 4173-88.
[http://dx.doi.org/10.1111/bph.13203] [PMID: 26033700]
[37]
Nie Y, Hu Y, Yu K, et al. Akt1 regulates pulmonary fibrosis via modulating IL-13 expression in macrophages. Innate Immun 2019; 25(7): 451-61.
[http://dx.doi.org/10.1177/1753425919861774] [PMID: 31299858]
[38]
Bolourani S, Brenner M, Wang P. The interplay of DAMPs, TLR4, and proinflammatory cytokines in pulmonary fibrosis. J Mol Med 2021; 99(10): 1373-84.
[http://dx.doi.org/10.1007/s00109-021-02113-y] [PMID: 34258628]
[39]
Xue Z, Zhao F, Sang X, et al. Combination therapy of tanshinone IIA and puerarin for pulmonary fibrosis via targeting IL6-JAK2-STAT3/STAT1 signaling pathways. Phytother Res 2021; 35(10): 5883-98.
[http://dx.doi.org/10.1002/ptr.7253] [PMID: 34427348]
[40]
Wang Y, Sang X, Shao R, et al. Xuanfei Baidu decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway. J Ethnopharmacol 2022; 283: 114701.
[http://dx.doi.org/10.1016/j.jep.2021.114701] [PMID: 34606948]
[41]
Yang J, Nie J, Ma X, Wei Y, Peng Y, Wei X. Targeting PI3K in cancer: Mechanisms and advances in clinical trials. Mol Cancer 2019; 18(1): 26.
[http://dx.doi.org/10.1186/s12943-019-0954-x] [PMID: 30782187]
[42]
Wang J, Hu K, Cai X, et al. Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis. Acta Pharm Sin B 2022; 12(1): 18-32.
[http://dx.doi.org/10.1016/j.apsb.2021.07.023] [PMID: 35127370]
[43]
Zhao H, Li C, Li L, et al. Baicalin alleviates bleomycin induced pulmonary fibrosis and fibroblast proliferation in rats via the PI3K/AKT signaling pathway. Mol Med Rep 2020; 21(6): 2321-34.
[http://dx.doi.org/10.3892/mmr.2020.11046] [PMID: 32323806]
[44]
Lu Y, Zhong W, Liu Y, et al. Anti-PD-L1 antibody alleviates pulmonary fibrosis by inducing autophagy via inhibition of the PI3K/Akt/mTOR pathway. Int Immunopharmacol 2022; 104: 108504.
[http://dx.doi.org/10.1016/j.intimp.2021.108504] [PMID: 35026657]
[45]
Cong LH, Li T, Wang H, et al. IL-17A-producing T cells exacerbate fine particulate matter-induced lung inflammation and fibrosis by inhibiting PI3K/Akt/mTOR-mediated autophagy. J Cell Mol Med 2020; 24(15): 8532-44.
[http://dx.doi.org/10.1111/jcmm.15475] [PMID: 32643865]
[46]
Qian W, Cai X, Qian Q, Zhang W, Wang D. Astragaloside IV modulates TGF-β1-dependent epithelial-mesenchymal transition in bleomycin-induced pulmonary fibrosis. J Cell Mol Med 2018; 22(9): 4354-65.
[http://dx.doi.org/10.1111/jcmm.13725] [PMID: 29971947]
[47]
Jiang F, Li S, Jiang Y, Chen Z, Wang T, Liu W. Fluorofenidone attenuates paraquat induced pulmonary fibrosis by regulating the PI3K/Akt/mTOR signaling pathway and autophagy. Mol Med Rep 2021; 23(6): 405.
[http://dx.doi.org/10.3892/mmr.2021.12044] [PMID: 33786626]
[48]
Saito S, Zhuang Y, Shan B, et al. Tubastatin ameliorates pulmonary fibrosis by targeting the TGFβ-PI3K-Akt pathway. PLoS One 2017; 12(10): e0186615.
[http://dx.doi.org/10.1371/journal.pone.0186615] [PMID: 29045477]
[49]
Shao S, Qu Z, Liang Y, et al. Iguratimod decreases bleomycin-induced pulmonary fibrosis in association with inhibition of TNF-α in mice. Int Immunopharmacol 2021; 99: 107936.
[http://dx.doi.org/10.1016/j.intimp.2021.107936] [PMID: 34284287]
[50]
Hou J, Ma T, Cao H, et al. TNF-α-induced NF-κB activation promotes myofibroblast differentiation of LR-MSCs and exacerbates bleomycin-induced pulmonary fibrosis. J Cell Physiol 2018; 233(3): 2409-19.
[http://dx.doi.org/10.1002/jcp.26112] [PMID: 28731277]
[51]
Lei L, Zhao C, Qin F, He ZY, Wang X, Zhong XN. Th17 cells and IL 17 promote the skin and lung inflammation and fibrosis process in a bleom ycin induced murine model of systemic sclerosis. Clin Exp Rheumatol 2016; 34(S100)(5): 14.
[PMID: 26750756]
[52]
Huang M, Wang YP, Zhu LQ, Cai Q, Li HH, Yang HF. MAPK pathway mediates epithelial-mesenchymal transition induced by paraquat in alveolar epithelial cells. Environ Toxicol 2016; 31(11): 1407-14.
[http://dx.doi.org/10.1002/tox.22146] [PMID: 25873302]
[53]
Chen H, Zhou X, Shi Y, Yang J. Roles of p38 MAPK and JNK in TGF-β1-induced human alveolar epithelial to mesenchymal transition. Arch Med Res 2013; 44(2): 93-8.
[http://dx.doi.org/10.1016/j.arcmed.2013.01.004] [PMID: 23376055]
[54]
Nguyen V, Pan F, Zhang G, Zhang Q, Lu Y. Panax notoginseng saponins regulate transforming growth factor-β1 through MAPK and Snail/TWIST1 signaling pathway to inhibit epithelial-mesenchymal transition of pulmonary fibrosis in A549 Cells. Evid Based Complement Alternat Med 2022; 2022: 3744618.
[http://dx.doi.org/10.1155/2022/3744618] [PMID: 35865337]
[55]
Zhu Y, Tan J, Xie H, Wang J, Meng X, Wang R. HIF-1α regulates EMT via the Snail and β-catenin pathways in paraquat poisoning-induced early pulmonary fibrosis. J Cell Mol Med 2016; 20(4): 688-97.
[http://dx.doi.org/10.1111/jcmm.12769] [PMID: 26781174]
[56]
Delbrel E, Soumare A, Naguez A, et al. HIF-1α triggers ER stress and CHOP-mediated apoptosis in alveolar epithelial cells, a key event in pulmonary fibrosis. Sci Rep 2018; 8(1): 17939.
[http://dx.doi.org/10.1038/s41598-018-36063-2] [PMID: 30560874]
[57]
Wang Z, Li X, Chen H, et al. Resveratrol alleviates bleomycin-induced pulmonary fibrosis via suppressing HIF-1α and NF-κB expression. Aging 2021; 13(3): 4605-16.
[http://dx.doi.org/10.18632/aging.202420] [PMID: 33495418]
[58]
Han M, Wang X, Wang J, et al. Ameliorative effects of epigallocatechin-3-gallate nanoparticles on 2,4-dinitrochlorobenzene induced atopic dermatitis: A potential mechanism of inflammation-related necroptosis. Front Nutr 2022; 9: 953646.
[http://dx.doi.org/10.3389/fnut.2022.953646] [PMID: 36017227]
[59]
Tang J, Diao P, Shu X, Li L, Xiong L. Quercetin and quercitrin attenuates the inflammatory response and oxidative stress in LPS-Induced RAW264.7 cells: In vitro assessment and a theoretical model. BioMed Res Int 2019; 2019: 7039802.
[http://dx.doi.org/10.1155/2019/7039802] [PMID: 31781635]
[60]
Zong Y, Chen F, Li S, Zhang H. Epigallocatechin-3-gallate (EGCG) prevents aminoglycosides-induced ototoxicity via anti-oxidative and anti-apoptotic pathways. Int J Pediatr Otorhinolaryngol 2021; 150: 110920.
[http://dx.doi.org/10.1016/j.ijporl.2021.110920] [PMID: 34500358]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy