{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T22:52:48Z","timestamp":1773183168774,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["2022R1C1C1002845"],"award-info":[{"award-number":["2022R1C1C1002845"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The influenza A virus poses a serious threat to human health and is an important global public health issue. The drugs currently used for treatment are becoming increasingly ineffective against influenza A viruses and require the development of new antiviral drugs. Angelica tenuissima Nakai (ATN), a traditional herbal medicine belonging to the Umbelliferae family, exhibits a broad range of pharmacological activities, including inflammation, headache, and cold symptoms. In the present study, based on target protein identification, functional enrichment analysis, and gene set comparisons, we first suggested that ATN has potential therapeutic effects against influenza A virus infection. Next, methylthiazol tetrazolium (MTT) and sulforhodamine B colorimetric (SRB) assay results revealed that ATN exhibited low cytotoxicity in Madin\u2013Darby canine kidney (MDCK) cells. The antiviral properties of ATN were observed against H1N1 and H3N2 virus strains. Microscopy confirmed the increased survival rate of the host cells. Further time-of-addition experiments revealed that the addition of ATN before virus adsorption showed similar results to the whole period of treatment. The pre- and co-treated groups showed lower levels of viral RNA (M1 protein). The results of this study suggest that ATN exhibits antiviral properties against the influenza A virus. These therapeutic properties of ATN can serve as a theoretical basis for further research on the applicability of ATN in the development of antiviral agents.<\/jats:p>","DOI":"10.3390\/pathogens13090761","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T08:46:22Z","timestamp":1725439582000},"page":"761","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antiviral Activity of Angelica Tenuissima Nakai against Influenza A Virus"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5061-2799","authenticated-orcid":false,"given":"Won-Jong","family":"Park","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gi-Sang","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Korean Medicine, Wonkwang University, Iksan 54538, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youn-Ho","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Oral Pharmacology, College of Dentistry, Wonkwang University, Iksan 54538, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/jpc.15847","article-title":"Respiratory syncytial virus epidemic during the COVID-19 pandemic","volume":"58","author":"Cooney","year":"2022","journal-title":"J. Paediatr. Child Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a038489","DOI":"10.1101\/cshperspect.a038489","article-title":"The Ecology and Evolution of Influenza Viruses","volume":"10","author":"Wille","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Fratty, I.S., Reznik-Balter, S., Nemet, I., Atari, N., Kliker, L., Sherbany, H., Keller, N., Stein, M., Mendelson, E., and Mandelboim, M. (2022). Outbreak of Influenza and Other Respiratory Viruses in Hospitalized Patients Alongside the SARS-CoV-2 Pandemic. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.902476"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.drudis.2008.03.024","article-title":"Pandemic and seasonal influenza: Therapeutic challenges","volume":"13","author":"Memoli","year":"2008","journal-title":"Drug Discov. Today"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e2243","DOI":"10.1002\/rmv.2243","article-title":"Influenza vaccines: Past, present, and future","volume":"32","author":"Kim","year":"2022","journal-title":"Rev. Med. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7033","DOI":"10.1016\/j.vaccine.2020.09.032","article-title":"Impact of pneumococcal conjugate vaccine on pneumonia hospitalization and mortality in children and elderly in Ecuador: Time series analyses","volume":"38","author":"Toscano","year":"2020","journal-title":"Vaccine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"518","DOI":"10.47102\/annals-acadmedsg.V37N6p518","article-title":"Antiviral drugs for the control of pandemic influenza virus","volume":"37","author":"Sugrue","year":"2008","journal-title":"Ann. Acad. Med. Singap."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.medj.2023.11.001","article-title":"Baloxavir marboxil use for critical human infection of avian influenza A H5N6 virus","volume":"5","author":"Guan","year":"2024","journal-title":"Med"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1750-2659.2009.00090.x","article-title":"Confronting the next influenza pandemic with anti-inflammatory and immunomodulatory agents: Why they are needed and how they might work","volume":"3","author":"Fedson","year":"2009","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1093\/jac\/dkq100","article-title":"Targeting pandemic influenza: A primer on influenza antivirals and drug resistance","volume":"65","author":"Moss","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lin, T.J., Lin, C.F., Chiu, C.H., Lee, M.C., and Horng, J.T. (2016). Inhibition of endosomal fusion activity of influenza virus by Rheum tanguticum (da-huang). Sci. Rep., 6.","DOI":"10.1038\/srep27768"},{"key":"ref_12","first-page":"779","article-title":"Chemical Constituents of the Root of Angelica tenuissima and their Anti-allergic Inflammatory Activity","volume":"12","author":"Choi","year":"2017","journal-title":"Nat. Prod. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s11655-017-2812-2","article-title":"Angelica tenuissima Nakai Ameliorates Cognitive Impairment and Promotes Neurogenesis in Mouse Model of Alzheimer\u2019s Disease","volume":"24","author":"Choi","year":"2018","journal-title":"Chin. J. Integr. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Safran, M., Dalah, I., Alexander, J., Rosen, N., Iny Stein, T., Shmoish, M., Nativ, N., Bahir, I., Doniger, T., and Krug, H. (2010). GeneCards Version 3: The human gene integrator. Database J. Biol. Databases Curation, 2010.","DOI":"10.1093\/database\/baq020"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"D833","DOI":"10.1093\/nar\/gkw943","article-title":"DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants","volume":"45","author":"Pinero","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.4014\/jmb.1812.02044","article-title":"Decursin and Z-Ligustilide in Angelica tenuissima Root Extract Fermented by Aspergillus oryzae Display Anti-Pigment Activity in Melanoma Cells","volume":"28","author":"Park","year":"2018","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jviromet.2006.05.023","article-title":"Validation of an automated real-time PCR protocol for detection and quantitation of HIV and HCV genomes in semen","volume":"137","author":"Pasquier","year":"2006","journal-title":"J. Virol. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lee, H.R., Lee, M.K., Kim, C.W., and Kim, M. (2020). TRIM Proteins and Their Roles in the Influenza Virus Life Cycle. Microorganisms, 8.","DOI":"10.3390\/microorganisms8091424"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1055\/s-0030-1250236","article-title":"Molecular targets of natural drug substances: Idiosyncrasies and preferences","volume":"76","author":"Imming","year":"2010","journal-title":"Planta Medica"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3109\/19390211.2015.1036190","article-title":"Safety and Health Benefits of Novel Dietary Supplements Consisting Multiple Phytochemicals, Vitamins, Minerals and Essential Fatty Acids in High Fat Diet Fed Rats","volume":"13","author":"Ramprasath","year":"2016","journal-title":"J. Diet. Suppl."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1021\/jf047932x","article-title":"Antioxidative activity of volatile extracts isolated from Angelica tenuissimae roots, peppermint leaves, pine needles, and sweet flag leaves","volume":"53","author":"Ka","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1055\/a-0901-1307","article-title":"Z-ligustilide and n-Butylidenephthalide Isolated from the Aerial Parts of Angelica tenuissima Inhibit Lipid Accumulation In Vitro and In Vivo","volume":"85","author":"Lee","year":"2019","journal-title":"Planta Medica"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S1473-3099(08)70070-7","article-title":"Confronting an influenza pandemic with inexpensive generic agents: Can it be done?","volume":"8","author":"Fedson","year":"2008","journal-title":"Lancet Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10602","DOI":"10.1128\/JVI.00939-15","article-title":"Intermonomer Interactions in Hemagglutinin Subunits HA1 and HA2 Affecting Hemagglutinin Stability and Influenza Virus Infectivity","volume":"89","author":"Wang","year":"2015","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8275","DOI":"10.1128\/JVI.02593-09","article-title":"An antibody against a novel and conserved epitope in the hemagglutinin 1 subunit neutralizes numerous H5N1 influenza viruses","volume":"84","author":"Oh","year":"2010","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.coviro.2012.02.005","article-title":"Broadly neutralizing antibodies against influenza virus and prospects for universal therapies","volume":"2","author":"Ekiert","year":"2012","journal-title":"Curr. Opin. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.1202617","article-title":"Computational design of proteins targeting the conserved stem region of influenza hemagglutinin","volume":"332","author":"Fleishman","year":"2011","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1086\/522609","article-title":"DAS181, a novel sialidase fusion protein, protects mice from lethal avian influenza H5N1 virus infection","volume":"196","author":"Belser","year":"2007","journal-title":"J. Infect. Dis."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/9\/761\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:48:34Z","timestamp":1760111314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/9\/761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,4]]},"references-count":28,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["pathogens13090761"],"URL":"https:\/\/doi.org\/10.3390\/pathogens13090761","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,4]]}}}