Login Register Cart 0
Generic placeholder image

Current Computer-Aided Drug Design

Editor-in-Chief

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

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

Deciphering the Underlying Mechanisms of Sanleng-Ezhu for the Treatment of Idiopathic Pulmonary Fibrosis Based on Network Pharmacology and Single-cell RNA Sequencing Data

Author(s): Xianqiang Zhou, Fang Tan, Suxian Zhang and Tiansong Zhang*

Volume 20, Issue 6, 2024

Published on: 22 August, 2023

Page: [888 - 910] Pages: 23

DOI: 10.2174/1573409920666230808120504

open access plus

Abstract

Aims: To decipher the underlying mechanisms of Sanleng-Ezhu for the treatment of idiopathic pulmonary fibrosis based on network pharmacology and single-cell RNA sequencing data.

Background: Idiopathic Pulmonary Fibrosis (IPF) is the most common type of interstitial lung disease. Although the combination of herbs Sanleng (SL) and Ezhu (EZ) has shown reliable efficacy in the management of IPF, its underlying mechanisms remain unknown.

Methods: Based on LC-MS/MS analysis and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, we identified the bioactive components of SL-EZ. After obtaining the IPF-related dataset GSE53845 from the Gene Expression Omnibus (GEO) database, we performed the differential expression analysis and the weighted gene co-expression network analysis (WGCNA), respectively. We obtained lowly and highly expressed IPF subtype gene sets by comparing Differentially Expressed Genes (DEGs) with the most significantly negatively and positively related IPF modules in WGCNA. Subsequently, we performed Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on IPF subtype gene sets. The low- and highexpression MCODE subgroup feature genes were identified by the MCODE plug-in and were adopted for Disease Ontology (DO), GO, and KEGG enrichment analyses. Next, we performed the immune cell infiltration analysis of the MCODE subgroup feature genes. Single-cell RNA sequencing analysis demonstrated the cell types which expressed different MCODE subgroup feature genes. Molecular docking and animal experiments validated the effectiveness of SL-EZ in delaying the progression of pulmonary fibrosis.

Results: We obtained 5 bioactive components of SL-EZ as well as their corresponding 66 candidate targets. After normalizing the samples of the GSE53845 dataset from the GEO database source, we obtained 1907 DEGs of IPF. Next, we performed a WGCNA analysis on the dataset and got 11 modules. Notably, we obtained 2 IPF subgroups by contrasting the most significantly up- and down-regulated modular genes in IPF with DEGs, respectively. The different IPF subgroups were compared with drugcandidate targets to obtain direct targets of action. After constructing the protein interaction networks between IPF subgroup genes and drug candidate targets, we applied the MCODE plug-in to filter the highest-scoring MCODE components. DO, GO, and KEGG enrichment analyses were applied to drug targets, IPF subgroup genes, and MCODE component signature genes. In addition, we downloaded the single-cell dataset GSE157376 from the GEO database. By performing quality control and dimensionality reduction, we clustered the scattered primary sample cells into 11 clusters and annotated them into 2 cell subtypes. Drug sensitivity analysis suggested that SL-EZ acts on different cell subtypes in IPF subgroups. Molecular docking revealed the mode of interaction between targets and their corresponding components. Animal experiments confirmed the efficacy of SL-EZ.

Conclusion: We found SL-EZ acted on epithelial cells mainly through the calcium signaling pathway in the lowly-expressed IPF subtype, while in the highly-expressed IPF subtype, SL-EZ acted on smooth muscle cells mainly through the viral infection, apoptosis, and p53 signaling pathway.

Keywords: Sanleng (SL), Ezhu (EZ), Idiopathic Pulmonary Fibrosis (IPF), network analysis, single-cell RNA sequencing, molecular docking, animal experiment.

« Previous Next »
Graphical Abstract

[1]
Somogyi, V.; Chaudhuri, N.; Torrisi, S.E.; Kahn, N.; Müller, V.; Kreuter, M. The therapy of idiopathic pulmonary fibrosis: What is next? Eur. Respir. Rev., 2019, 28(153), 190021.
[http://dx.doi.org/10.1183/16000617.0021-2019] [PMID: 31484664]
[2]
Raghu, G.; Weycker, D.; Edelsberg, J.; Bradford, W.Z.; Oster, G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med., 2006, 174(7), 810-816.
[http://dx.doi.org/10.1164/rccm.200602-163OC] [PMID: 16809633]
[3]
Arjun, S.; Patel, D.; Sanivarapu, R.; Iqbal, J.; Anjum, F. Case report of severe pulmonary fibrosis as a sequelae of COVID-19 Infection. Chest, 2020, 158(4), A433-A434.
[http://dx.doi.org/10.1016/j.chest.2020.08.422]
[4]
Combet, M.; Pavot, A.; Savale, L.; Humbert, M.; Monnet, X. Rapid onset honeycombing fibrosis in spontaneously breathing patient with COVID-19. Eur. Respir. J., 2020, 56(2), 2001808.
[http://dx.doi.org/10.1183/13993003.01808-2020] [PMID: 32631838]
[5]
Schwensen, H.F.; Borreschmidt, L.K.; Storgaard, M.; Redsted, S.; Christensen, S.; Madsen, L.B. Fatal pulmonary fibrosis: A post- COVID-19 autopsy case. J. Clin. Pathol., 2020, jclinpath-2020-206879.
[http://dx.doi.org/10.1136/jclinpath-2020-206879]
[6]
Wendisch, D.; Dietrich, O.; Mari, T.; von Stillfried, S.; Ibarra, I.L.; Mittermaier, M.; Mache, C.; Chua, R.L.; Knoll, R.; Timm, S.; Brumhard, S.; Krammer, T.; Zauber, H.; Hiller, A.L.; Pascual-Reguant, A.; Mothes, R.; Bülow, R.D.; Schulze, J.; Leipold, A.M.; Djudjaj, S.; Erhard, F.; Geffers, R.; Pott, F.; Kazmierski, J.; Radke, J.; Pergantis, P.; Baßler, K.; Conrad, C.; Aschenbrenner, A.C.; Sawitzki, B.; Landthaler, M.; Wyler, E.; Horst, D.; Hippenstiel, S.; Hocke, A.; Heppner, F.L.; Uhrig, A.; Garcia, C.; Machleidt, F.; Herold, S.; Elezkurtaj, S.; Thibeault, C.; Witzenrath, M.; Cochain, C.; Suttorp, N.; Drosten, C.; Goffinet, C.; Kurth, F.; Schultze, J.L.; Radbruch, H.; Ochs, M.; Eils, R.; Müller-Redetzky, H.; Hauser, A.E.; Luecken, M.D.; Theis, F.J.; Conrad, C.; Wolff, T.; Boor, P.; Selbach, M.; Saliba, A.E.; Sander, L.E. SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis. Cell, 2021, 184(26), 6243-6261.e27.
[http://dx.doi.org/10.1016/j.cell.2021.11.033] [PMID: 34914922]
[7]
George, P.M.; Wells, A.U.; Jenkins, R.G. Pulmonary fibrosis and COVID-19: The potential role for antifibrotic therapy. Lancet Respir. Med., 2020, 8(8), 807-815.
[http://dx.doi.org/10.1016/S2213-2600(20)30225-3] [PMID: 32422178]
[8]
Richeldi, L.; Collard, H.R.; Jones, M.G. Idiopathic pulmonary fibrosis. Lancet, 2017, 389(10082), 1941-1952.
[http://dx.doi.org/10.1016/S0140-6736(17)30866-8] [PMID: 28365056]
[9]
Lederer, D.J.; Martinez, F.J. Idiopathic pulmonary fibrosis. N. Engl. J. Med., 2018, 378(19), 1811-1823.
[http://dx.doi.org/10.1056/NEJMra1705751] [PMID: 29742380]
[10]
King, C.S.; Nathan, S.D. Idiopathic pulmonary fibrosis: Effects and optimal management of comorbidities. Lancet Respir. Med., 2017, 5(1), 72-84.
[http://dx.doi.org/10.1016/S2213-2600(16)30222-3] [PMID: 27599614]
[11]
Raghu, G.; Rochwerg, B.; Zhang, Y.; Garcia, C.A.C.; Azuma, A.; Behr, J.; Brozek, J.L.; Collard, H.R.; Cunningham, W.; Homma, S.; Johkoh, T.; Martinez, F.J.; Myers, J.; Protzko, S.L.; Richeldi, L.; Rind, D.; Selman, M.; Theodore, A.; Wells, A.U.; Hoogsteden, H.; Schünemann, H.J. An official ATS/ERS/JRS/ALAT clinical practice guideline: Treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am. J. Respir. Crit. Care Med., 2015, 192(2), e3-e19.
[http://dx.doi.org/10.1164/rccm.201506-1063ST] [PMID: 26177183]
[12]
Borie, R.; Justet, A.; Beltramo, G.; Manali, E.D.; Pradère, P.; Spagnolo, P.; Crestani, B. Pharmacological management of IPF. Respirology, 2016, 21(4), 615-625.
[http://dx.doi.org/10.1111/resp.12778] [PMID: 27072575]
[13]
George, P.M.; Patterson, C.M.; Reed, A.K.; Thillai, M. Lung transplantation for idiopathic pulmonary fibrosis. Lancet Respir. Med., 2019, 7(3), 271-282.
[http://dx.doi.org/10.1016/S2213-2600(18)30502-2] [PMID: 30738856]
[14]
Clay, E.; Cristeau, O.; Chafaie, R.; Pinta, A.; Mazaleyrat, B.; Cottin, V. Cost-effectiveness of pirfenidone compared to all available strategies for the treatment of idiopathic pulmonary fibrosis in France. J. Mark. Access Health Policy, 2019, 7(1), 1626171.
[http://dx.doi.org/10.1080/20016689.2019.1626171] [PMID: 31275535]
[15]
Verpoorte, R.; Choi, Y.H.; Kim, H.K. Ethnopharmacology and systems biology: A perfect holistic match. J. Ethnopharmacol., 2005, 100(1-2), 53-56.
[http://dx.doi.org/10.1016/j.jep.2005.05.033] [PMID: 16026949]
[16]
Zhang, S. The effect of typical couplet medicinals on bleomycin-induced pulmonary fibrosis in mice based on data mining; Fudan University: Shanghai, 2018.
[17]
Jia, J.; Li, X.; Ren, X.; Liu, X.; Wang, Y.; Dong, Y.; Wang, X.; Sun, S.; Xu, X.; Li, X.; Song, R.; Ma, J.; Yu, A.; Fan, Q.; Wei, J.; Yan, X.; Wang, X.; She, G. Sparganii Rhizoma: A review of traditional clinical application, processing, phytochemistry, pharmacology, and toxicity. J. Ethnopharmacol., 2021, 268, 113571.
[http://dx.doi.org/10.1016/j.jep.2020.113571] [PMID: 33181282]
[18]
Zhou, Y.; Xie, M.; Song, Y.; Wang, W.; Zhao, H.; Tian, Y.; Wang, Y.; Bai, S.; Zhao, Y.; Chen, X.; She, G. Two traditional chinese medicines curcumae radix and curcumae rhizoma: An ethnopharmacology, phytochemistry, and pharmacology review. Evid. Based Complement. Alternat. Med., 2016, 2016, 1-30.
[http://dx.doi.org/10.1155/2016/4973128] [PMID: 27057197]
[19]
Lee, T.K.; Lee, D.; Lee, S.R.; Ko, Y.J.; Sung Kang, K.; Chung, S.J.; Kim, K.H. Sesquiterpenes from Curcuma zedoaria rhizomes and their cytotoxicity against human gastric cancer AGS cells. Bioorg. Chem., 2019, 87, 117-122.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.015] [PMID: 30884305]
[20]
Li, S.; Zhang, B. Traditional Chinese medicine network pharmacology: Theory, methodology and application. Chin. J. Nat. Med., 2013, 11(2), 110-120.
[http://dx.doi.org/10.1016/S1875-5364(13)60037-0] [PMID: 23787177]
[21]
Chen, X.; Yu, J.; Lei, H.; Li, L.; Liu, X.; Liu, B.; Xie, Y.; Fang, H. Exploring the mechanism of buyang huanwu decoction alleviating restenosis by regulating VSMC phenotype switching and proliferation by network pharmacology and molecular docking. Curr. Computeraided Drug Des., 2023, 19(6), 451-464.
[PMID: 36740793]
[22]
Shan, W.; Yang, Z.; Zhao, Y.; Hu, Y.; Yan, R.; Wu, X.; Huang, J.; Lin, M. Bioactive phytochemicals and molecular mechanisms of artemisiae capillariae against drug induced liver injury based on network pharmacology. Curr. Computeraided Drug Des., 2023, 19(6), 476-489.
[PMID: 36856178]
[23]
Guo, D.; Jin, J.; Liu, J.; Ren, M.; He, Y. Network pharmacological study of compound kushen injection in esophageal cancer. Curr. Computeraided Drug Des., 2023, 19(5), 367-381.
[PMID: 36635923]
[24]
Heath, J.R.; Ribas, A.; Mischel, P.S. Single-cell analysis tools for drug discovery and development. Nat. Rev. Drug Discov., 2016, 15(3), 204-216.
[http://dx.doi.org/10.1038/nrd.2015.16] [PMID: 26669673]
[25]
Luo, Y.; Fan, R. Deconvolution analysis of cell‐type expression from bulk tissues by integrating with single‐cell expression reference. Genet. Epidemiol., 2022, 46(8), 615-628.
[http://dx.doi.org/10.1002/gepi.22494] [PMID: 35788983]
[26]
Nascimento, I.J.S.; de Aquino, T.M.; da Silva-Júnior, E.F. The new era of drug discovery: The power of Computer-aided Drug Design (CADD). Lett. Drug Des. Discov., 2022, 19(11), 951-955.
[http://dx.doi.org/10.2174/1570180819666220405225817]
[27]
dos Santos Nascimento, I.J.; da Silva-Júnior, E.F.; de Aquino, T.M. Molecular modeling targeting transmembrane serine protease 2 (TMPRSS2) as an alternative drug target against coronaviruses. Curr. Drug Targets, 2022, 23(3), 240-259.
[http://dx.doi.org/10.2174/1389450122666210809090909]
[28]
dos Santos Nascimento, I.J.; de Aquino, T.M.; da Silva-Júnior, E.F. Drug repurposing: A strategy for discovering inhibitors against emerging viral infections. Curr. Med. Chem., 2021, 28(15), 2887-2942.
[http://dx.doi.org/10.2174/0929867327666200812215852]
[29]
Li, C.; Du, X.; Liu, Y.; Liu, Q.Q.; Zhi, W.B.; Wang, C.L.; Zhou, J.; Li, Y.; Zhang, H. A systems pharmacology approach for identifying the multiple mechanisms of action for the rougui-fuzi herb pair in the treatment of cardiocerebral vascular diseases. Evid. Based Complement. Alternat. Med., 2020, 2020, 1-17.
[http://dx.doi.org/10.1155/2020/5196302] [PMID: 32025235]
[30]
Kim, S.; Chen, J.; Cheng, T.; Gindulyte, A.; He, J.; He, S.; Li, Q.; Shoemaker, B.A.; Thiessen, P.A.; Yu, B.; Zaslavsky, L.; Zhang, J.; Bolton, E.E. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res., 2021, 49(D1), D1388-D1395.
[http://dx.doi.org/10.1093/nar/gkaa971] [PMID: 33151290]
[31]
Bateman, A.; Martin, M-J.; Orchard, S.; Magrane, M.; Agivetova, R.; Ahmad, S.; Alpi, E.; Bowler-Barnett, E.H.; Britto, R.; Bursteinas, B.; Bye-A-Jee, H.; Coetzee, R.; Cukura, A.; Da Silva, A.; Denny, P.; Dogan, T.; Ebenezer, T.G.; Fan, J.; Castro, L.G.; Garmiri, P.; Georghiou, G.; Gonzales, L.; Hatton-Ellis, E.; Hussein, A.; Ignatchenko, A.; Insana, G.; Ishtiaq, R.; Jokinen, P.; Joshi, V.; Jyothi, D.; Lock, A.; Lopez, R.; Luciani, A.; Luo, J.; Lussi, Y.; MacDougall, A.; Madeira, F.; Mahmoudy, M.; Menchi, M.; Mishra, A.; Moulang, K.; Nightingale, A.; Oliveira, C.S.; Pundir, S.; Qi, G.; Raj, S.; Rice, D.; Lopez, M.R.; Saidi, R.; Sampson, J.; Sawford, T.; Speretta, E.; Turner, E.; Tyagi, N.; Vasudev, P.; Volynkin, V.; Warner, K.; Watkins, X.; Zaru, R.; Zellner, H.; Bridge, A.; Poux, S.; Redaschi, N.; Aimo, L.; Argoud-Puy, G.; Auchincloss, A.; Axelsen, K.; Bansal, P.; Baratin, D.; Blatter, M-C.; Bolleman, J.; Boutet, E.; Breuza, L.; Casals-Casas, C.; de Castro, E.; Echioukh, K.C.; Coudert, E.; Cuche, B.; Doche, M.; Dornevil, D.; Estreicher, A.; Famiglietti, M.L.; Feuermann, M.; Gasteiger, E.; Gehant, S.; Gerritsen, V.; Gos, A.; Gruaz-Gumowski, N.; Hinz, U.; Hulo, C.; Hyka-Nouspikel, N.; Jungo, F.; Keller, G.; Kerhornou, A.; Lara, V.; Le Mercier, P.; Lieberherr, D.; Lombardot, T.; Martin, X.; Masson, P.; Morgat, A.; Neto, T.B.; Paesano, S.; Pedruzzi, I.; Pilbout, S.; Pourcel, L.; Pozzato, M.; Pruess, M.; Rivoire, C.; Sigrist, C.; Sonesson, K.; Stutz, A.; Sundaram, S.; Tognolli, M.; Verbregue, L.; Wu, C.H.; Arighi, C.N.; Arminski, L.; Chen, C.; Chen, Y.; Garavelli, J.S.; Huang, H.; Laiho, K.; McGarvey, P.; Natale, D.A.; Ross, K.; Vinayaka, C.R.; Wang, Q.; Wang, Y.; Yeh, L-S.; Zhang, J.; Ruch, P.; Teodoro, D. UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Res., 2021, 49(D1), D480-D489.
[http://dx.doi.org/10.1093/nar/gkaa1100] [PMID: 33237286]
[32]
DePianto, D.J.; Chandriani, S.; Abbas, A.R.; Jia, G.; N’Diaye, E.N.; Caplazi, P.; Kauder, S.E.; Biswas, S.; Karnik, S.K.; Ha, C.; Modrusan, Z.; Matthay, M.A.; Kukreja, J.; Collard, H.R.; Egen, J.G.; Wolters, P.J.; Arron, J.R. Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis. Thorax, 2015, 70(1), 48-56.
[http://dx.doi.org/10.1136/thoraxjnl-2013-204596] [PMID: 25217476]
[33]
Barrett, T.; Wilhite, S.E.; Ledoux, P.; Evangelista, C.; Kim, I.F.; Tomashevsky, M.; Marshall, K.A.; Phillippy, K.H.; Sherman, P.M.; Holko, M.; Yefanov, A.; Lee, H.; Zhang, N.; Robertson, C.L.; Serova, N.; Davis, S.; Soboleva, A. NCBI GEO: Archive for functional genomics data sets-update. Nucleic Acids Res., 2012, 41(D1), D991-D995.
[http://dx.doi.org/10.1093/nar/gks1193] [PMID: 23193258]
[34]
Debrabant, B. The null hypothesis of GSEA, and a novel statistical model for competitive gene set analysis. Bioinformatics, 2017, 33(9), 1271-1277.
[http://dx.doi.org/10.1093/bioinformatics/btw803] [PMID: 28453686]
[35]
Langfelder, P.; Horvath, S. WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics, 2008, 9(1), 559.
[http://dx.doi.org/10.1186/1471-2105-9-559] [PMID: 19114008]
[36]
Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res., 2021, 49(D1), D605-D612.
[http://dx.doi.org/10.1093/nar/gkaa1074] [PMID: 33237311]
[37]
Tang, Y.; Li, M.; Wang, J.; Pan, Y.; Wu, F.X. CytoNCA: A cytoscape plugin for centrality analysis and evaluation of protein interaction networks. Biosystems, 2015, 127, 67-72.
[http://dx.doi.org/10.1016/j.biosystems.2014.11.005] [PMID: 25451770]
[38]
Berman, H.; Henrick, K.; Nakamura, H. Announcing the worldwide protein data bank. Nat. Struct. Mol. Biol., 2003, 10(12), 980.
[http://dx.doi.org/10.1038/nsb1203-980] [PMID: 14634627]
[39]
Lohning, A.E.; Levonis, S.M.; Williams-Noonan, B.; Schweiker, S.S. A practical guide to molecular docking and homology modelling for medicinal chemists. Curr. Top. Med. Chem., 2017, 17(18), 2023-2040.
[http://dx.doi.org/10.2174/1568026617666170130110827] [PMID: 28137238]
[40]
Olson, A.L.; Gifford, A.H.; Inase, N.; Fernández Pérez, E.R.; Suda, T. The epidemiology of idiopathic pulmonary fibrosis and interstitial lung diseases at risk of a progressive-fibrosing phenotype. Eur. Respir. Rev., 2018, 27(150), 180077.
[http://dx.doi.org/10.1183/16000617.0077-2018] [PMID: 30578336]
[41]
Selman, M.; Pardo, A. Revealing the pathogenic and aging-related mechanisms of the enigmatic idiopathic pulmonary fibrosis. An integral model. Am. J. Respir. Crit. Care Med., 2014, 189(10), 1161-1172.
[http://dx.doi.org/10.1164/rccm.201312-2221PP] [PMID: 24641682]
[42]
Sgalla, G.; Biffi, A.; Richeldi, L. Idiopathic pulmonary fibrosis: Diagnosis, epidemiology and natural history. Respirology, 2016, 21(3), 427-437.
[http://dx.doi.org/10.1111/resp.12683] [PMID: 26595062]
[43]
Richeldi, L.; Rubin, A.S.; Avdeev, S.; Udwadia, Z.F.; Xu, Z.J. Idiopathic pulmonary fibrosis in BRIC countries: The cases of Brazil, Russia, India, and China. BMC Med., 2015, 13(1), 237.
[http://dx.doi.org/10.1186/s12916-015-0495-0] [PMID: 26399999]
[44]
Gao, L.; Tang, H.; He, H.; Liu, J.; Mao, J.; Ji, H.; Lin, H.; Wu, T. Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats. Front. Pharmacol., 2015, 6, 215.
[http://dx.doi.org/10.3389/fphar.2015.00215] [PMID: 26483688]
[45]
Li, R.F.; Chen, X.Y.; Xu, Y.; Feng, F.C.; He, H.L.; Zhou, X.M. Inhibitory effects of alkaline extract from the pericarp of Citrus reticulata Blanco on collagen behavior in bleomycin-induced pulmonary fibrosis. J. Ethnopharmacol., 2021, 269, 113761.
[http://dx.doi.org/10.1016/j.jep.2020.113761] [PMID: 33383114]
[46]
Zhang, Y.; Gu, L.; Xia, Q.; Tian, L.; Qi, J.; Cao, M. Radix astragali and radix angelicae sinensis in the treatment of idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Front. Pharmacol., 2020, 11, 415.
[http://dx.doi.org/10.3389/fphar.2020.00415] [PMID: 32425767]
[47]
Zhang, S.; Wu, H.; Liu, J.; Gu, H.; Li, X.; Zhang, T. Medication regularity of pulmonary fibrosis treatment by contemporary traditional Chinese medicine experts based on data mining. J. Thorac. Dis., 2018, 10(3), 1775-1787.
[http://dx.doi.org/10.21037/jtd.2018.03.11] [PMID: 29707332]
[48]
Wu, Q.L.; Cheng, Y.Q.; Liu, A.J.; Zhang, W.D. Formononetin recovered injured nerve functions by enhancing synaptic plasticity in ischemic stroke rats. Biochem. Biophys. Res. Commun., 2020, 525(1), 67-72.
[http://dx.doi.org/10.1016/j.bbrc.2020.02.015] [PMID: 32081422]
[49]
Sugimoto, M.; Ko, R.; Goshima, H.; Koike, A.; Shibano, M.; Fujimori, K. Formononetin attenuates H2O2-induced cell death through decreasing ROS level by PI3K/Akt-Nrf2-activated antioxidant gene expression and suppressing MAPK-regulated apoptosis in neuronal SH-SY5Y cells. Neurotoxicology, 2021, 85, 186-200.
[http://dx.doi.org/10.1016/j.neuro.2021.05.014] [PMID: 34077701]
[50]
Zhao, X.; Qu, G.; Song, C.; Li, R.; Liu, W.; Lv, C.; Song, X.; Zhang, J.; Li, M. Novel formononetin-7-sal ester ameliorates pulmonary fibrosis via MEF2c signaling pathway. Toxicol. Appl. Pharmacol., 2018, 356, 15-24.
[http://dx.doi.org/10.1016/j.taap.2018.07.005] [PMID: 29990528]
[51]
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]
[52]
Wu, A.G.; Zeng, W.; Wong, V.K.W.; Zhu, Y.Z.; Lo, A.C.Y.; Liu, L.; Law, B.Y.K. Hederagenin and α-hederin promote degradation of proteins in neurodegenerative diseases and improve motor deficits in MPTP-mice. Pharmacol. Res., 2017, 115, 25-44.
[http://dx.doi.org/10.1016/j.phrs.2016.11.002] [PMID: 27838509]
[53]
Akhtar, M.; Shaukat, A.; Zahoor, A.; Chen, Y.; Wang, Y.; Yang, M.; Umar, T.; Guo, M.; Deng, G. Anti-inflammatory effects of Hederacoside-C on Staphylococcus aureus induced inflammation via TLRs and their downstream signal pathway in vivo and in vitro. Microb. Pathog., 2019, 137, 103767.
[http://dx.doi.org/10.1016/j.micpath.2019.103767] [PMID: 31580956]
[54]
Wolf, A.; Gosens, R.; Meurs, H.; Häberlein, H. Pre-treatment with α-hederin increases β-adrenoceptor mediated relaxation of airway smooth muscle. Phytomedicine, 2011, 18(2-3), 214-218.
[http://dx.doi.org/10.1016/j.phymed.2010.05.010] [PMID: 20637581]
[55]
Ma, W.; Huang, Q.; Xiong, G.; Deng, L.; He, Y. The protective effect of Hederagenin on pulmonary fibrosis by regulating the Ras/JNK/NFAT4 axis in rats. Biosci. Biotechnol. Biochem., 2020, 84(6), 1131-1138.
[http://dx.doi.org/10.1080/09168451.2020.1721263] [PMID: 32024440]
[56]
Antwi, A.O.; Obiri, D.D.; Osafo, N. Stigmasterol modulates allergic airway inflammation in guinea pig model of ovalbumin-induced asthma. Mediators Inflamm., 2017, 2017, 1-11.
[http://dx.doi.org/10.1155/2017/2953930] [PMID: 28555089]
[57]
Mendez, E.; Calzada, C.; Ocharan, E.; Sierra, A.; Castillo, C.; Ramirez, I.; Meaney, E.; Meaney, A.; Asbun, J.; Miliar, A.; Herrera, J.; Ceballos, G. Differential expression of α1-adrenergic receptor subtypes in coronary microvascular endothelial cells in culture. Eur. J. Pharmacol., 2006, 546(1-3), 127-133.
[http://dx.doi.org/10.1016/j.ejphar.2006.06.070] [PMID: 16904663]
[58]
Lin, C.H.; Nfor, O.N.; Ho, C.C.; Hsu, S.Y.; Tantoh, D.M.; Liaw, Y.C.; Daria, M.R.; Chen, C.H.; Liaw, Y.P. Association of ADH1B polymorphism and alcohol consumption with increased risk of intracerebral hemorrhagic stroke. J. Transl. Med., 2021, 19(1), 227.
[http://dx.doi.org/10.1186/s12967-021-02904-4] [PMID: 34051793]
[59]
Zhao, L.; Yang, F.; Xu, K.; Cao, H.; Zheng, G.Y.; Zhang, Y.; Li, J.; Cui, H.; Chen, X.; Zhu, Z.; He, H.; Mo, X.; Kennedy, B.K.; Suh, Y.; Zeng, Y.; Tian, X.L. Common genetic variants of the β2-adrenergic receptor affect its translational efficiency and are associated with human longevity. Aging Cell, 2012, 11(6), 1094-1101.
[http://dx.doi.org/10.1111/acel.12011] [PMID: 23020224]
[60]
Bossard, F.; Silantieff, É.; Lavazais-Blancou, E.; Robay, A.; Sagan, C.; Rozec, B.; Gauthier, C. β1, β2, and β3 adrenoceptors and Na+/H+ exchanger regulatory factor 1 expression in human bronchi and their modifications in cystic fibrosis. Am. J. Respir. Cell Mol. Biol., 2011, 44(1), 91-98.
[http://dx.doi.org/10.1165/rcmb.2009-0372OC] [PMID: 20203292]
[61]
Moon, Y.K.; Kim, H.; Kim, S.; Lim, S-W.; Kim, D.K. Influence of antidepressant treatment on SLC6A4 methylation in korean patients with major depression. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2022, 192(1-2), 28-37.
[http://dx.doi.org/10.1002/ajmg.b.32921] [PMID: 36094099]
[62]
Liu, L.; Hu, Y.; Lu, Y.; Hu, L.; Gao, C.; Nie, S. Sex-dependent DNA hypermethylation of SLC6A4 in patients with schizophrenia. Neurosci. Lett., 2022, 769, 136394.
[http://dx.doi.org/10.1016/j.neulet.2021.136394] [PMID: 34910986]
[63]
Cybulska, A.M.; Szkup, M.; Schneider-Matyka, D.; Skonieczna-Żydecka, K.; Kaczmarczyk, M.; Jurczak, A.; Wieder-Huszla, S.; Karakiewicz, B.; Grochans, E. Depressive symptoms among middle-aged women—understanding the cause. Brain Sci., 2020, 11(1), 26.
[http://dx.doi.org/10.3390/brainsci11010026] [PMID: 33379297]
[64]
Buffin-Meyer, B.; Crassous, P.A.; Delage, C.; Denis, C.; Schaak, S.; Paris, H. EGF receptor transactivation and PI3-kinase mediate stimulation of ERK by α2A-adrenoreceptor in intestinal epithelial cells: A role in wound healing. Eur. J. Pharmacol., 2007, 574(2-3), 85-93.
[http://dx.doi.org/10.1016/j.ejphar.2007.07.014] [PMID: 17655843]
[65]
Tutton, P.J.; Barkla, D.H. Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review). Anticancer Res., 1987, 7(1), 1-12.
[PMID: 3032070]
[66]
Epperson, S.A.; Brunton, L.L.; Ramirez-Sanchez, I.; Villarreal, F. Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts. Am. J. Physiol. Cell Physiol., 2009, 296(5), C1171-C1177.
[http://dx.doi.org/10.1152/ajpcell.00290.2008] [PMID: 19244482]

Rights & Permissions Print Cite
Article Metrics
47
3
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy