{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T06:18:04Z","timestamp":1775110684616,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Coxsackievirus infection can cause various diseases such as myocarditis and encephalitis, posing a serious threat to human health. However, there are currently no specific therapeutic drugs or effective vaccines for Coxsackievirus infection, so exploring new anti-Coxsackievirus agents is of great significance. Geniposide, an iridoid glycoside component from traditional Chinese medicine Gardenia jasminoides, has shown multiple pharmacological activities, but its antiviral effect against Coxsackievirus and related mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      This study verified the antiviral activity of geniposide against coxsackievirus\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and combined network pharmacology with molecular docking to explore the candidate targets and pathways underlying its effects against coxsackievirus B3 (CVB3).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments confirmed that geniposide exhibited significant inhibitory activity against CVB3. Compared with the virus control group, geniposide treatment significantly reduced the degree of pathological changes in HEp-2 and Vero cells infected with CVB3 and effectively inhibited virus plaque formation in a concentration-dependent manner. The 50% effective concentrations (EC\n                      <jats:sub>50<\/jats:sub>\n                      ) of geniposide in HEp-2 and Vero cells were 165.2\u00a0\u03bcg\/mL and 142.5\u00a0\u03bcg\/mL, respectively. Network pharmacology analysis identified AKT1, STAT1, MMP9, CASP3, MAPK14, and MAPK1 as core potential targets of geniposide against CVB3. Molecular docking results predicted that geniposide could form stable binding conformations with these six core targets, providing a theoretical molecular basis for its antiviral effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study confirmed that geniposide inhibits CVB3 replication\n                      <jats:italic>in vitro<\/jats:italic>\n                      in a concentration-dependent manner. Network pharmacology and molecular docking predicted that its anti-CVB3 activity may be associated with binding to core targets including AKT1, STAT1, MMP9, CASP3, MAPK14, and MAPK1. These results provide a hypothetical framework for further mechanistic validation of geniposide against CVB3. This study offers experimental evidence supporting geniposide as a potential anti-coxsackievirus lead compound for future preclinical research, and also provides a novel direction for the prevention and treatment of coxsackievirus infection.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1785779","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:23:56Z","timestamp":1775107436000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Study on the inhibitory effect of geniposide on coxsackievirus and its mechanism"],"prefix":"10.3389","volume":"17","author":[{"given":"Jianbo","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuliang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengxin","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1002\/bab.2233","article-title":"Caspase-3: structure, function, and biotechnological aspects","volume":"69","author":"Asadi","year":"2022","journal-title":"Biotechnol. Appl. Biochem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3892\/ijmm.2017.3008","article-title":"The PI3K\/Akt\/mTOR pathway is involved in CVB3-induced autophagy of HeLa cells","volume":"40","author":"Chang","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.12659\/msm.899804","article-title":"Berberine restricts coxsackievirus B type 3 replication via inhibition of c-Jun N-Terminal kinase (JNK) and p38 MAPK activation in vitro","volume":"23","author":"Dai","year":"2017","journal-title":"Med. Sci. Monit."},{"key":"B4","doi-asserted-by":"publisher","first-page":"4289","DOI":"10.1128\/jvi.78.8.4289-4298.2004","article-title":"Protein kinase B\/Akt regulates coxsackievirus B3 replication through a mechanism which is not caspase dependent","volume":"78","author":"Esfandiarei","year":"2004","journal-title":"J. Virol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.4014\/jmb.1904.04050","article-title":"Scutellaria baicalensis inhibits coxsackievirus B3-Induced myocarditis via AKT and p38 pathways","volume":"29","author":"Fu","year":"2019","journal-title":"J. Microbiol. Biotechnol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"109303","DOI":"10.1016\/j.fsi.2023.109303","article-title":"Effects of geniposide on innate immunity and antiviral activity of scyllaparamamosain","volume":"145","author":"Gong","year":"2024","journal-title":"Fish. Shellfish Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2567","DOI":"10.1038\/s41401-024-01341-5","article-title":"Geniposide alleviates heart failure with preserved ejection fraction in mice by regulating cardiac oxidative stress via MMP2\/SIRT1\/GSK3beta pathway","volume":"45","author":"Han","year":"2024","journal-title":"Acta Pharmacol. Sin."},{"key":"B8","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1186\/s12967-019-2077-y","article-title":"The protective role of microRNA-21 against coxsackievirus B3 infection through targeting the MAP2K3\/P38 MAPK signaling pathway","volume":"17","author":"He","year":"2019","journal-title":"J. Transl. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.fsi.2022.05.037","article-title":"Natural component geniposide enhances survival rate of crayfish Procambarus clarkii infected with white spot syndrome virus","volume":"126","author":"Huang","year":"2022","journal-title":"Fish. Shellfish Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.chom.2012.11.009","article-title":"An ERK-p38 subnetwork coordinates host cell apoptosis and necrosis during coxsackievirus B3 infection","volume":"13","author":"Jensen","year":"2013","journal-title":"Cell Host Microbe"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e803","DOI":"10.1038\/cddis.2013.331","article-title":"Overexpression of 4EBP1, p70S6K, Akt1 or Akt2 differentially promotes coxsackievirus B3-induced apoptosis in HeLa cells","volume":"4","author":"Li","year":"2013","journal-title":"Cell Death Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"7480512","DOI":"10.1155\/2019\/7480512","article-title":"Antioxidative property and molecular mechanisms underlying geniposide-mediated therapeutic effects in diabetes mellitus and cardiovascular disease","volume":"2019","author":"Li","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s13020-024-00981-3","article-title":"Geniposide for treating atherosclerotic cardiovascular disease: a systematic review on its biological characteristics, pharmacology, pharmacokinetics, and toxicology","volume":"19","author":"Li","year":"2024","journal-title":"Chin. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"157107","DOI":"10.1016\/j.phymed.2025.157107","article-title":"Dehydrotumulosic acid: a potential glucocorticoid receptor agonist with anti-coxsackievirus activity","volume":"146","author":"Li","year":"","journal-title":"Phytomedicine"},{"key":"B15","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13321-025-01017-0","article-title":"A resource description framework (RDF) model of named entity co-occurrences in biomedical literature and its integration with PubChemRDF","volume":"17","author":"Li","year":"","journal-title":"J. Cheminform"},{"key":"B16","doi-asserted-by":"publisher","first-page":"9007","DOI":"10.3390\/ijms25169007","article-title":"STAT3 increases CVB3 replication and acute pancreatitis and myocarditis pathology via impeding nuclear translocation of STAT1 and interferon-stimulated gene expression","volume":"25","author":"Liang","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3319","DOI":"10.3390\/molecules27103319","article-title":"Updated pharmacological effects, molecular mechanisms, and therapeutic potential of natural product geniposide","volume":"27","author":"Liu","year":"2022","journal-title":"Molecules"},{"key":"B18","doi-asserted-by":"publisher","first-page":"274","DOI":"10.3390\/vaccines11020274","article-title":"Vaccines against group B coxsackieviruses and their importance","volume":"11","author":"Mone","year":"2023","journal-title":"Vaccines (Basel)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1451611","DOI":"10.3389\/fmolb.2024.1451611","article-title":"MMP9: link between neuropathy and colorectal cancer?","volume":"11","author":"Regalado","year":"2024","journal-title":"Front. Mol. Biosci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1146\/annurev-biochem-081720-114505","article-title":"MAPK-activated protein kinases: servant or partner?","volume":"91","author":"Ronkina","year":"2022","journal-title":"Annu. Rev. Biochem."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22101689","article-title":"A review on the phytochemistry, pharmacology, pharmacokinetics and toxicology of geniposide, a natural product","volume":"22","author":"Shan","year":"2017","journal-title":"Molecules"},{"key":"B22","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1089\/jmf.2023.0104","article-title":"Role of nutraceuticals in obesity management: a mechanism and prospective supported by molecular docking studies","volume":"27","author":"Singab","year":"2024","journal-title":"J. Med. Food"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1615\/CritRevOncog.2024056533","article-title":"Molecular docking: an emerging tool for target-based cancer therapy","volume":"30","author":"Uppathi","year":"2025","journal-title":"Crit. Rev. Oncog."},{"key":"B24","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1002\/bdd.1869","article-title":"Pharmacokinetics, bioavailability and tissue distribution of geniposide following intravenous and peroral administration to rats","volume":"35","author":"Wang","year":"2014","journal-title":"Biopharm. Drug Dispos."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2441391","DOI":"10.1080\/22221751.2024.2441391","article-title":"Research progress and application prospects of animal models of group B coxsackievirus infections","volume":"14","author":"Weng","year":"2025","journal-title":"Emerg. Microbes Infect."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1007\/s00380-020-01607-y","article-title":"The protection effects of survivin in the cell model of CVB3-induced viral myocarditis","volume":"35","author":"Wu","year":"2020","journal-title":"Heart Vessels"},{"key":"B27","doi-asserted-by":"publisher","first-page":"176935","DOI":"10.1016\/j.ejphar.2024.176935","article-title":"Viral myocarditis: from molecular mechanisms to therapeutic prospects","volume":"982","author":"Yan","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"B28","first-page":"669","article-title":"Expression of matrix metalloproteinase-9 in myocardium of mice with viral myocarditis","volume":"13","author":"Yang","year":"2011","journal-title":"Zhongguo Dang Dai Er Ke Za Zhi"},{"key":"B29","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s12272-012-0101-3","article-title":"Bioactivity-guided fractionation and analysis of compounds with anti-influenza virus activity from Gardenia jasminoides ellis","volume":"35","author":"Yang","year":"2012","journal-title":"Arch. Pharm. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"950817","DOI":"10.1155\/2014\/950817","article-title":"Antiviral activity of total flavonoid extracts from Selaginella moellendorffii hieron against coxsackie virus B3 in vitro and in vivo","volume":"2014","author":"Yin","year":"2014","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"218","DOI":"10.18433\/jpps32911","article-title":"Progress and prospects of research ideas and methods in the network pharmacology of traditional Chinese medicine","volume":"25","author":"Yuan","year":"2022","journal-title":"J. Pharm. Pharm. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2180951","DOI":"10.1080\/21505594.2023.2180951","article-title":"Immune mechanisms of group B coxsackievirus induced viral myocarditis","volume":"14","author":"Zhang","year":"2023","journal-title":"Virulence"},{"key":"B33","doi-asserted-by":"publisher","first-page":"156018","DOI":"10.1016\/j.phymed.2024.156018","article-title":"Geniposide attenuates influenza virus-induced pneumonia by regulating inflammatory cytokines production. Evidences to elucidate the followed pathway","volume":"135","author":"Zhang","year":"2024","journal-title":"Phytomedicine"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1610676","DOI":"10.3389\/fphar.2025.1610676","article-title":"A potential herbal component for the future treatment of fatty liver disease: geniposide from gardenia","volume":"16","author":"Zhang","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e2087","DOI":"10.1002\/rmv.2087","article-title":"A review and meta-analysis of the epidemiology and clinical presentation of coxsackievirus A6 causing hand-foot-mouth disease in China and global implications","volume":"30","author":"Zhao","year":"2020","journal-title":"Rev. Med. Virol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1785779\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:23:57Z","timestamp":1775107437000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1785779\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,2]]},"references-count":35,"alternative-id":["10.3389\/fphar.2026.1785779"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1785779","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,2]]},"article-number":"1785779"}}