{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:56:04Z","timestamp":1779378964373,"version":"3.53.1"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["Grant nos. 81473547 and 81673829"],"award-info":[{"award-number":["Grant nos. 81473547 and 81673829"]}],"id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Complement Med Ther"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Globally, more than 170 million people are infected with hepatitis C virus, a major cause of cirrhosis and hepatocellular carcinoma. The Yinchenhao Decoction (YCHD) is a classic formula comprising three herbal medicines. This decoction have long been used in China for clinically treating acute and chronic infectious hepatitis and other liver and gallbladder damp heat-accumulation disorders.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this study, we identified 32 active ingredients and 200 hepatitis C proteins and established a compound-predicted target network and a hepatitis C protein\u2013protein interaction network by using Cytoscape 3.6.1. Then, we systematically analyzed the potential targets of the YCHD for the treatment of hepatitis C. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by the Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>This study adopted a network pharmacology approach, mainly comprising target prediction, network construction, module detection, functional enrichment analysis, and molecular docking to systematically investigate the mechanisms of action of the YCHD in hepatitis C. The targets of the YCHD in the treatment of hepatitis C mainly involved PIK3CG, CASP3, BCL2, CASP8, and MMP1. The module and pathway enrichment analyses showed that the YCHD had the potential to influence varieties of biological pathways, including the TNF signaling pathway, Ras signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, and pathways in cancer, that play an important role in the pathogenesis of hepatitis C.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The results of this study preliminarily verified the basic pharmacological effects and related mechanisms of the YCHD in the treatment of hepatitis C.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12906-020-2823-y","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T13:03:00Z","timestamp":1581512580000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A bioinformatics investigation into the pharmacological mechanisms of the effect of the Yinchenhao decoction on hepatitis C based on network pharmacology"],"prefix":"10.1186","volume":"20","author":[{"given":"Jingyuan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinkui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1617-6110","authenticated-orcid":false,"given":"Jiarui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan Shan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengwei","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,12]]},"reference":[{"key":"2823_CR1","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.phymed.2018.04.015","volume":"54","author":"H Sun","year":"2019","unstructured":"Sun H, Zhang AH, Yang L, Li MX, Fang H, Xie J, Wang XJ. High-throughput chinmedomics strategy for discovering the quality-markers and potential targets for Yinchenhao decoction. Phytomedicine. 2019;54:328\u201338.","journal-title":"Phytomedicine"},{"key":"2823_CR2","doi-asserted-by":"publisher","first-page":"108863","DOI":"10.1016\/j.biopha.2019.108863","volume":"114","author":"FF Cai","year":"2019","unstructured":"Cai FF, Bian YQ, Wu R, Sun Y, Chen XL, Yang MD, Zhang QR, Hu Y, Sun MY, Su SB. Yinchenhao decoction suppresses rat liver fibrosis involved in an apoptosis regulation mechanism based on network pharmacology and transcriptomic analysis. Biomed Pharmacother. 2019;114:108863.","journal-title":"Biomed Pharmacother"},{"key":"2823_CR3","doi-asserted-by":"publisher","first-page":"4583","DOI":"10.3892\/mmr.2017.7149","volume":"16","author":"J Huang","year":"2017","unstructured":"Huang J, Cheung F, Tan HY, Hong M, Wang N, Yang J, Feng Y, Zheng Q. Identification of the active compounds and significant pathways of yinchenhao decoction based on network pharmacology. Mol Med Rep. 2017;16:4583\u201392.","journal-title":"Mol Med Rep"},{"key":"2823_CR4","doi-asserted-by":"publisher","first-page":"8352","DOI":"10.3748\/wjg.v21.i27.8352","volume":"21","author":"HB Zhou","year":"2015","unstructured":"Zhou HB, Chen JM, Shao LM, Chen ZG. Apoptosis of human pancreatic carcinoma cell-1 cells induced by yin Chen Hao decoction. World J Gastroenterol. 2015;21:8352\u20137.","journal-title":"World J Gastroenterol"},{"key":"2823_CR5","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/S2095-4964(15)60185-6","volume":"13","author":"SL Jiang","year":"2015","unstructured":"Jiang SL, Hu XD, Liu P. Immunomodulation and liver protection of Yinchenhao decoction against concanavalin A-induced chronic liver injury in mice. J Integr Med. 2015;13:262\u20138.","journal-title":"J Integr Med"},{"issue":"6","key":"2823_CR6","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1056\/NEJMc1908197","volume":"381","author":"DL Thomas","year":"2019","unstructured":"Thomas DL. Global elimination of chronic hepatitis. Reply N Engl J Med. 2019;381(6):589\u201390.","journal-title":"Reply N Engl J Med"},{"key":"2823_CR7","first-page":"379","volume":"27","author":"P Thomas","year":"2019","unstructured":"Thomas P, Brown Richard JP. Hepatitis C Virus Trends Microbiol. 2019;27:379\u201380.","journal-title":"Hepatitis C Virus Trends Microbiol"},{"key":"2823_CR8","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1007\/s12664-018-0920-3","volume":"37","author":"G Amit","year":"2018","unstructured":"Amit G, Singh BD, Rakesh A. Hepatitis C virus infection and chronic renal disease: a review. Indian J Gastroenterol. 2018;37:492\u2013503.","journal-title":"Indian J Gastroenterol"},{"key":"2823_CR9","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/j.jfma.2018.11.005","volume":"118","author":"CY Chu","year":"2019","unstructured":"Chu CY, Cheng CH, Chen HL, Lin IT, Wu CH, Lee YK, Bair MJ. Long-term histological change in chronic hepatitis C patients who had received peginterferon plus ribavirin therapy with sustained virological response. J Formos Med Assoc. 2019;118:1129\u201337.","journal-title":"J Formos Med Assoc"},{"issue":"12","key":"2823_CR10","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1038\/nrgastro.2013.163","volume":"10","author":"PM Trembling","year":"2013","unstructured":"Trembling PM, Tanwar S, Rosenberg WM, Desheiko GM. Treatment decisions and contemporary versus pending treatments for hepatitis C. Nat Rev Gastroenterol Hepatol. 2013;10(12):713\u201328.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"9","key":"2823_CR11","first-page":"82","volume":"26","author":"CY Yu","year":"2013","unstructured":"Yu CY. Treatment of 65 cases of chronic hepatitis C with Yinchenhao decoction and Western medicine. Western J Chin Med. 2013;26(9):82\u20133.","journal-title":"Western J Chin Med"},{"key":"2823_CR12","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/j.cell.2007.08.021","volume":"130","author":"TW Corson","year":"2007","unstructured":"Corson TW, Crews CM. Molecular understanding and modern application of traditional medicines: triumphs and trials. Cell. 2007;130:769\u201374.","journal-title":"Cell"},{"key":"2823_CR13","first-page":"456747","volume":"2013","author":"B Zhang","year":"2013","unstructured":"Zhang B, Wang X, Li S. An integrative platform of TCM network pharmacology and its application on a herbal formula, Qing-Luo-Yin. Evid Based Complement Alternat Med. 2013;2013:456747.","journal-title":"Evid Based Complement Alternat Med"},{"key":"2823_CR14","doi-asserted-by":"crossref","unstructured":"Li Z, Hou J, Deng Y, Zhi H, Wu W, Yan B, Chen T, Tu J, Zhu Z, Wu W, Guo DA. Exploring the protective effects of Danqi Tongmai tablet on acute myocardial ischemia rats by comprehensive metabolomics profiling. Phytomedicine. 2019:152918.","DOI":"10.1016\/j.phymed.2019.152918"},{"key":"2823_CR15","first-page":"1368371","volume":"2019","author":"S Long","year":"2019","unstructured":"Long S, Yuan C, Wang Y, Zhang J, Li G. Network pharmacology analysis of in gene-phenotype. Evid Based Complement Alternat Med. 2019;2019:1368371.","journal-title":"Evid Based Complement Alternat Med"},{"key":"2823_CR16","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12918-018-0606-6","volume":"12","author":"YF Cao","year":"2018","unstructured":"Cao YF, Wang SF, Li X, Zhang YL, Qiao YJ. The anticancer mechanism investigation of Tanshinone II by pharmacological clustering in protein network. BMC Syst Biol. 2018;12:90.","journal-title":"BMC Syst Biol"},{"key":"2823_CR17","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S1674-6384(16)60018-7","volume":"8","author":"YQ Zhang","year":"2016","unstructured":"Zhang YQ, Mao X, Guo QY, Lin N, Li S. Network pharmacology-based approaches capture essence of Chinese herbal medicines. Chinese Herb Med. 2016;8:107\u201316.","journal-title":"Chinese Herb Med"},{"key":"2823_CR18","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1758-2946-6-13","volume":"6","author":"J Ru","year":"2014","unstructured":"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;6:13.","journal-title":"J Cheminform"},{"key":"2823_CR19","doi-asserted-by":"publisher","first-page":"531","DOI":"10.3389\/fphar.2016.00477","volume":"7","author":"F Yi","year":"2016","unstructured":"Yi F, Sun L, Xu LJ, Peng Y, Liu HB, He CN, Xiao PG. In silico approach for anti-thrombosis drug discovery: P2YR structure-based TCMs screening. Front Pharmacol. 2016;7:531.","journal-title":"Front Pharmacol"},{"key":"2823_CR20","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.jep.2015.09.016","volume":"175","author":"Y Li","year":"2015","unstructured":"Li Y, Wang J, Xiao Y, Wang Y, Chen S, Yang Y, Lu A, Zhang S. A systems pharmacology approach to investigate the mechanisms of action of semen Strychni and Tripterygium wilfordii hook F for treatment of rheumatoid arthritis. J Ethnopharmacol. 2015;175:301\u201314.","journal-title":"J Ethnopharmacol"},{"key":"2823_CR21","doi-asserted-by":"publisher","first-page":"D1069","DOI":"10.1093\/nar\/gkv1230","volume":"44","author":"H Yang","year":"2016","unstructured":"Yang H, Qin C, Li YH, Tao L, Zhou J, Yu CY, Xu F, Chen Z, Zhu F, Chen YZ. Therapeutic target database update 2016: enriched resource for bench to clinical drug target and targeted pathway information. Nucleic Acids Res. 2016;44:D1069\u201374.","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"2823_CR22","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1038\/ng0407-426","volume":"39","author":"RB Altman","year":"2007","unstructured":"Altman RB, PharmGKB. A logical home for knowledge relating genotype to drug response phenotype. Nat Genet. 2007;39(4):426.","journal-title":"Nat Genet"},{"key":"2823_CR23","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.1016\/j.wneu.2019.04.125","volume":"129","author":"H Zhao","year":"2019","unstructured":"Zhao H, Li ST, Zhu J, Hua XM, Wan L. Analysis of peripheral blood Cells' Transcriptome in patients with subarachnoid hemorrhage from ruptured aneurysm reveals potential biomarkers. World Neurosurg. 2019;129:e16\u201322.","journal-title":"World Neurosurg"},{"key":"2823_CR24","doi-asserted-by":"publisher","first-page":"111905","DOI":"10.1016\/j.jep.2019.111905","volume":"241","author":"N Wang","year":"2019","unstructured":"Wang N, Zhu F, Shen M, Qiu L, Tang M, Xia H, Chen L, Yuan Y, Ma S, Chen K. Network pharmacology-based analysis on bioactive anti-diabetic compounds in Potentilla discolor bunge. J Ethnopharmacol. 2019;241:111905.","journal-title":"J Ethnopharmacol"},{"key":"2823_CR25","doi-asserted-by":"publisher","first-page":"111826","DOI":"10.1016\/j.jep.2019.111826","volume":"238","author":"E Shawky","year":"2019","unstructured":"Shawky E. Prediction of potential cancer-related molecular targets of north African plants constituents using network pharmacology-based analysis. J Ethnopharmacol. 2019;238:111826.","journal-title":"J Ethnopharmacol"},{"key":"2823_CR26","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12918-016-0382-0","volume":"11","author":"D Kapetis","year":"2017","unstructured":"Kapetis D, Sassone J, Yang Y, Galbardi B, Xenakis MN, Westra RL, Szklarczyk R, Lindsey P, Faber CG, Gerrits M, Merkies IS, Dib-Hajj SD, Mantegazza M, Waxman SG, Lauria G, PROPANE Study Group. Network topology of NaV1.7 mutations in sodium channel-related painful disorders. BMC Syst Biol. 2017;11:28.","journal-title":"BMC Syst Biol"},{"issue":"Suppl 3","key":"2823_CR27","doi-asserted-by":"publisher","first-page":"S31","DOI":"10.1186\/1471-2164-10-S3-S31","volume":"10","author":"Min Zhao","year":"2009","unstructured":"Zhao M, Qu H. Human liver rate-limiting enzymes influence metabolic flux via branch points and inhibitors. BMC Genomics. 2009:S31.","journal-title":"BMC Genomics"},{"key":"2823_CR28","doi-asserted-by":"publisher","first-page":"212061","DOI":"10.1155\/2015\/212061","volume":"2015","author":"T Melak","year":"2015","unstructured":"Melak T, Gakkhar S. Comparative genome and network centrality analysis to identify drug targets of mycobacterium tuberculosis H37Rv. Biomed Res Int. 2015;2015:212061.","journal-title":"Biomed Res Int"},{"key":"2823_CR29","doi-asserted-by":"publisher","first-page":"D464","DOI":"10.1093\/nar\/gky1004","volume":"47","author":"SK Burley","year":"2019","unstructured":"Burley SK, Berman HM, Bhikadiya C, Bi C, Chen L, Di Costanzo L, Christie C, Dalenberg K, Duarte JM, Dutta S, Feng Z, Ghosh S, Goodsell DS, Green RK, Guranovic V, Guzenko D, Hudson BP, 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 YP, 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:D464\u201374.","journal-title":"Nucleic Acids Res"},{"key":"2823_CR30","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1021\/acs.jcim.9b00041","volume":"59","author":"HY Chen","year":"2019","unstructured":"Chen HY, Chen JQ, Li JY, Huang HJ, Chen X, Zhang HY, Chen CY. Deep learning and random Forest approach for finding the optimal traditional Chinese medicine formula for treatment of Alzheimer's disease. J Chem Inf Model. 2019;59:1605\u201323.","journal-title":"J Chem Inf Model"},{"key":"2823_CR31","doi-asserted-by":"publisher","first-page":"W507","DOI":"10.1093\/nar\/gkw335","volume":"44","author":"K Hsin","year":"2016","unstructured":"Hsin K, Matsuoka Y, Asai Y, Kyota K, Tokiko W, Yoshihiro K, Hiroaki K. Systems Dock: a web serve for network pharmacology-based prediction and analysis. Nucleic Acids Res. 2016;44:W507\u201313.","journal-title":"Nucleic Acids Res"},{"key":"2823_CR32","first-page":"4188","volume":"17","author":"R Ancuceanu","year":"2019","unstructured":"Ancuceanu R, Dinu M, Neaga I, Laszlo FG, Boda D. Development of QSAR machine learning-based models to forecast the effect of substances on malignant melanoma cells. Oncol Lett. 2019;17:4188\u201396.","journal-title":"Oncol Lett"},{"key":"2823_CR33","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.5713\/ajas.18.0718","volume":"32","author":"P Gao","year":"2019","unstructured":"Gao P, Cheng Z, Li M, Zhang M, Le B, Zhang W, Song P, Guo X, Li B, Cao G. Selection of candidate genes affecting meat quality and preliminary exploration of related molecular mechanisms in the Mashen pig. Asian-australas J Anim Sci. 2019;32:1084\u201394.","journal-title":"Asian-australas J Anim Sci"},{"key":"2823_CR34","first-page":"7826769","volume":"2019","author":"JF Liu","year":"2019","unstructured":"Liu JF, Hu AN, Zan JF, Wang P, You QY, Tan AH. Network pharmacology deciphering mechanisms of volatiles of granule for the treatment of Alzheimer's disease. Evid Based Complement Alternat Med. 2019;2019:7826769.","journal-title":"Evid Based Complement Alternat Med"},{"key":"2823_CR35","doi-asserted-by":"publisher","first-page":"653","DOI":"10.33594\/000000046","volume":"52","author":"D Wang","year":"2019","unstructured":"Wang D, Gu C, Liu M, Liu G, Liu H, Wang Y. Analysis of Long noncoding RNA expression profile in human pulmonary microvascular endothelial cells exposed to lipopolysaccharide. Cell Physiol Biochem. 2019;52:653\u201367.","journal-title":"Cell Physiol Biochem"},{"key":"2823_CR36","doi-asserted-by":"crossref","unstructured":"Sun YW, Wang Y, Guo ZF, Du KC, Meng DL. Systems Pharmacological Approach to Investigate the Mechanism of for Application to Alzheimer's Disease. Molecules. 2019;24 undefined.","DOI":"10.3390\/molecules24081499"},{"key":"2823_CR37","doi-asserted-by":"publisher","first-page":"e83922","DOI":"10.1371\/journal.pone.0083922","volume":"8","author":"H Kun-Yi","year":"2013","unstructured":"Kun-Yi H, Samik G, Hiroaki K. Combining machine learning systems and multiple docking Sinulation packages to improve docking prediction reliability for network pharmacology. PLoS One. 2013;8:e83922.","journal-title":"PLoS One"},{"key":"2823_CR38","doi-asserted-by":"publisher","first-page":"15543","DOI":"10.1038\/s41598-017-15812-9","volume":"7","author":"Q Kong","year":"2018","unstructured":"Kong Q, Ma Y, Yu J, Chen X. Predicted molecular targets and pathways for germacronr, curdione, and furanodiene in the treatment of breast cancer using a bioinformactics approach. Sci Rep. 2018;7:15543.","journal-title":"Sci Rep"},{"issue":"6","key":"2823_CR39","first-page":"1792","volume":"40","author":"ZY Wu","year":"2017","unstructured":"Wu ZY, Li JR, Huang MH, Cheng JJ, Li H, Chen JH, Lv XQ, Peng ZG, Jiang JD. Internal driving factors leading to extrahepatic manifestation of the hepatitis C virus infection. Int J Mol Med. 2017;40(6):1792\u2013802.","journal-title":"Int J Mol Med"},{"key":"2823_CR40","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.compbiolchem.2016.10.006","volume":"65","author":"S Patel","year":"2016","unstructured":"Patel S. In silico analysis of hepatitis C virus (HCV) polyprotein domains and their comparison with other pathogens and allergens to gain insight on pathogenicity mechanisms. Comput Biol Chem. 2016;65:91\u2013102.","journal-title":"Comput Biol Chem"},{"key":"2823_CR41","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1111\/j.1478-3231.2007.01613.x","volume":"27","author":"N Kemmer","year":"2007","unstructured":"Kemmer N, Neff GW. Managing chronic hepatitis C in the difficult-to-treat patient. Liver Int. 2007;27:1297\u2013310.","journal-title":"Liver Int"},{"key":"2823_CR42","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1002\/lt.25488","volume":"25","author":"S Shi","year":"2019","unstructured":"Shi S, Verstegen MMA, Mezzanotte L, de Jonge J, L\u00f6wik CWGM, van der Laan LJW. Necroptotic cell death in liver transplantation and underlying diseases: mechanisms and clinical perspective. Liver Transpl. 2019;25:1091\u2013104.","journal-title":"Liver Transpl"},{"key":"2823_CR43","doi-asserted-by":"crossref","unstructured":"Barathan M, Mohamed R, Yong YK, Kannan M, Vadivelu J, Saeidi A, Larsson M, Shankar EM. Viral Persistence and Chronicity in Hepatitis C Virus Infection: Role of T-Cell Apoptosis, Senescence and Exhaustion. Cells. 2018;7 undefined.","DOI":"10.20944\/preprints201810.0033.v1"},{"key":"2823_CR44","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1007\/s10620-018-5401-0","volume":"64","author":"Y Liu","year":"2019","unstructured":"Liu Y, Wang W, Zou Z, Hu Z, Fan Q, Xiong J. Hepatitis C virus entry into macrophages\/monocytes mainly depends on the phagocytosis of macrophages. Dig Dis Sci. 2019;64:1226\u201337.","journal-title":"Dig Dis Sci"},{"issue":"4","key":"2823_CR45","doi-asserted-by":"publisher","first-page":"239","DOI":"10.3390\/pathogens8040239","volume":"8","author":"SM Ma","year":"2019","unstructured":"Ma SM, Mao Q, Yi L, Zhao MQ, Chen JD. Apoptosis, autophagy, and Pyroptosis: immune escape strategies for persistent infection and pathogenesis of classical swine fever virus. Pathogens. 2019;8(4):239.","journal-title":"Pathogens"},{"key":"2823_CR46","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1053\/he.2000.7123","volume":"31","author":"F Calabrese","year":"2000","unstructured":"Calabrese F, Pontisso P, Pettenazzo E, Benvegn\u00f9 L, Vario A, Chemello L, Alberti A, Valente M. Liver cell apoptosis in chronic hepatitis C correlates with histological but not biochemical activity or serum HCV-RNA levels. Hepatology. 2000;31:1153\u20139.","journal-title":"Hepatology"},{"key":"2823_CR47","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1046\/j.1365-2893.2003.00452.x","volume":"10","author":"J Kountouras","year":"2003","unstructured":"Kountouras J, Zavos C, Chatzopoulos D. Apoptosis in hepatitis C. J Viral Hepat. 2003;10:335\u201342.","journal-title":"J Viral Hepat"},{"key":"2823_CR48","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1046\/j.1365-2893.2001.00316.x","volume":"8","author":"S Pianko","year":"2001","unstructured":"Pianko S, Patella S, Ostapowicz G, Desmond P, Sievert W. Fas-mediated hepatocyte apoptosis is increased by hepatitis C virus infection and alcohol consumption, and may be associated with hepatic fibrosis: mechanisms of liver cell injury in chronic hepatitis C virus infection. J Viral Hepat. 2001;8:406\u201313.","journal-title":"J Viral Hepat"},{"key":"2823_CR49","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1126\/science.3874430","volume":"228","author":"Y Tsujimoto","year":"1985","unstructured":"Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the bcl-2 gene in human follicular lymphoma. Science. 1985;228:1440\u20133.","journal-title":"Science"},{"issue":"3","key":"2823_CR50","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1128\/JVI.71.3.1739-1746.1997","volume":"71","author":"JG Teodoro","year":"1997","unstructured":"Teodoro JG, Branton PE. Regulation of apoptosis by viral gene products. J Virol. 1997;71(3):1739\u201346.","journal-title":"J Virol"},{"key":"2823_CR51","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1007\/s12291-012-0219-6","volume":"27","author":"EF Eskander","year":"2012","unstructured":"Eskander EF, Abd-Rabou AA, Mohamed MS, Yahya SM, Shaker OG. Does HCV patients who have BCL2 43Ala genotype and Normal GH1 levels can achieve response to IFN based therapy? Indian J Clin Biochem. 2012;27:344\u201350.","journal-title":"Indian J Clin Biochem"},{"key":"2823_CR52","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.matbio.2015.01.004","volume":"44-46","author":"Sergio Duarte","year":"2015","unstructured":"Duarte S, Baber J, Fujii T, Coito AJ. Matrix metalloproteinases in liver injury, repair and fibrosis. Matrix Biol. 2015:147\u201356.","journal-title":"Matrix Biology"},{"key":"2823_CR53","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1053\/gast.2003.50063","volume":"124","author":"Y Iimuro","year":"2003","unstructured":"Iimuro Y, Nishio T, Morimoto T, Nitta T, Stefanovic B, Choi SK, Brenner DA, Yamaoka Y. Delivery of matrix metalloproteinase-1 attenuates established liver fibrosis in the rat. Gastroenterology. 2003;124:445\u201358.","journal-title":"Gastroenterology"},{"key":"2823_CR54","doi-asserted-by":"publisher","first-page":"5288","DOI":"10.4049\/jimmunol.178.8.5288","volume":"178","author":"JA Fallowfield","year":"2007","unstructured":"Fallowfield JA, Mizuno M, Kendall TJ, Constandinou CM, Benyon RC, Duffield JS, Iredale JP. Scar-associated macrophages are a major source of hepatic matrix metalloproteinase-13 and facilitate the resolution of murine hepatic fibrosis. J Immunol. 2007;178:5288\u201395.","journal-title":"J Immunol"},{"issue":"s3","key":"2823_CR55","doi-asserted-by":"publisher","first-page":"S88","DOI":"10.1111\/j.1440-1746.2006.04586.x","volume":"21","author":"Yuan-Ping Han","year":"2006","unstructured":"Han HP. Matrix metalloproteinases, the pros and cons, in liver fibrosis. J Gastroenterol Hepatol. 2006:S88\u201391.","journal-title":"Journal of Gastroenterology and Hepatology"},{"issue":"4","key":"2823_CR56","first-page":"532","volume":"36","author":"Y Liu","year":"2016","unstructured":"Liu Y, Feng Y, Weng CJ, Xia XS. Hepatitis C inflammation and abnormal cell signaling pathway. Chem Life. 2016;36(4):532\u20137.","journal-title":"Chem Life"},{"key":"2823_CR57","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.clim.2016.01.014","volume":"164","author":"X Pang","year":"2016","unstructured":"Pang X, Song H, Zhang Q, Tu Z, Niu J. Hepatitis C virus regulates the production of monocytic myeloid-derived suppressor cells from peripheral blood mononuclear cells through PI3K pathway and autocrine signaling. Clin Immunol. 2016;164:57\u201364.","journal-title":"Clin Immunol"},{"key":"2823_CR58","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1007\/s10495-014-1084-y","volume":"20","author":"M Barathan","year":"2015","unstructured":"Barathan M, Gopal K, Mohamed R, Elleg\u00e5rd R, Saeidi A, Vadivelu J, Ansari AW, Rothan HA, Ravishankar Ram M, Zandi K, Chang LY, Vignesh R, Che KF, Kamarulzaman A, Velu V, Larsson M, Kamarul T, Shankar EM. Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes. Apoptosis. 2015;20:466\u201380.","journal-title":"Apoptosis"},{"key":"2823_CR59","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12954-019-0303-9","volume":"16","author":"M Maticic","year":"2019","unstructured":"Maticic M, Zorman JV, Gregorcic S, Schatz E, Lazarus JV. Changes to the national strategies, plans and guidelines for the treatment of hepatitis C in people who inject drugs between 2013 and 2016: a cross-sectional survey of 34 European countries. Harm Reduct J. 2019;16:32.","journal-title":"Harm Reduct J"}],"container-title":["BMC Complementary Medicine and Therapies"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-020-2823-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12906-020-2823-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-020-2823-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T12:21:25Z","timestamp":1613046085000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccomplementalternmed.biomedcentral.com\/articles\/10.1186\/s12906-020-2823-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,12]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["2823"],"URL":"https:\/\/doi.org\/10.1186\/s12906-020-2823-y","relation":{},"ISSN":["2662-7671"],"issn-type":[{"value":"2662-7671","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,12]]},"assertion":[{"value":"2 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"50"}}