{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T00:13:30Z","timestamp":1793924010997,"version":"4.8.0"},"reference-count":32,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 109-2221-E-019-035"],"award-info":[{"award-number":["MOST 109-2221-E-019-035"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 110-2221-E-019 -003 -MY2"],"award-info":[{"award-number":["MOST 110-2221-E-019 -003 -MY2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Phellinus linteus, a medicinal mushroom with an ancient history in traditional medicine, serves as a valuable raw material for functional foods. While previous studies have shown promising antiviral effects, the present work is the most comprehensive investigation of P. linteus mycelial extracts and active compounds thereof against the H1N1 influenza virus infection in in vitro and animal models. Antiviral activity was evaluated using three treatment approaches (preventive, co-treatment, and therapeutic) in MDCK cells infected with H1N1 virus. In vivo studies employed male BALB\/c mice exposed to aerosolized H1N1 virus (1.6 \u00d7 106 PFU\/mL). In the animal experiment, mice received either P. linteus mycelia powder (PL) at 1000 mg\/kg\/day or PLw\/PLe at 350 mg\/kg\/day for 7 days before and after infection. Ethanol extracts (PLe) demonstrated superior antiviral properties compared to water extracts (PLw) in cell survival and viral inhibition tests. Animal studies revealed that both PL and PLe significantly improved recovery after H1N1 infection, with survival rates of 60% and 40%, respectively, versus 25% in controls. The treatments effectively restored depleted immune cell populations, indicating broad immunomodulatory effects. These findings highlight the potential of P. linteus as a functional food ingredient with promising therapeutic applications against viral infections through its action on both innate and adaptive immune responses.<\/jats:p>","DOI":"10.3390\/foods14234047","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:04:57Z","timestamp":1764151497000},"page":"4047","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phellinus linteus Mycelia Extracts Show Potent Antiviral and Immunomodulatory Effects in H1N1 Influenza Virus-Infected Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-9591","authenticated-orcid":false,"given":"I-Chen","family":"Li","sequence":"first","affiliation":[{"name":"Biotech Research Institute, Grape King Bio Ltd., Long Tan District, Taoyuan City 325, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Lin","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chinese Culture University, Taipei 111, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Ting","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Food Science and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung City 202, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn-Huey","family":"Chiang","sequence":"additional","affiliation":[{"name":"Biotech Research Institute, Grape King Bio Ltd., Long Tan District, Taoyuan City 325, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8613-344X","authenticated-orcid":false,"given":"Tsung-Ju","family":"Li","sequence":"additional","affiliation":[{"name":"Biotech Research Institute, Grape King Bio Ltd., Long Tan District, Taoyuan City 325, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Genomics Research Center, Academia Sinica, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Chu","family":"Chen","sequence":"additional","affiliation":[{"name":"Biotech Research Institute, Grape King Bio Ltd., Long Tan District, Taoyuan City 325, Taiwan"},{"name":"Institute of Food Science and Technology, National Taiwan University, Taipei City 106, Taiwan"},{"name":"Institute of BioPharmaceutical Science, National Sun Yat-sen University, Kaohsiung 804, Taiwan"},{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Zhong-Li District, Taoyuan City 320, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5079-5839","authenticated-orcid":false,"given":"Chang-Jer","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Food Science and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung City 202, Taiwan"},{"name":"Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"A6","DOI":"10.1016\/j.vaccine.2020.09.048","article-title":"The disease burden of influenza beyond respiratory illness","volume":"39","author":"Macias","year":"2021","journal-title":"Vaccine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13276","DOI":"10.1111\/irv.13276","article-title":"Recent Advances, Approaches and Challenges in the Development of Universal Influenza Vaccines","volume":"18","author":"Lim","year":"2024","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Batool, S., Chokkakula, S., and Song, M.S. (2023). Influenza Treatment: Limitations of Antiviral Therapy and Advantages of Drug Combination Therapy. Microorganisms, 11.","DOI":"10.3390\/microorganisms11010183"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chen, W., Tan, H., Liu, Q., Zheng, X., Zhang, H., Liu, Y., and Xu, L. (2019). A Review: The Bioactivities and Pharmacological Applications of Phellinus linteus. Molecules, 24.","DOI":"10.3390\/molecules24101888"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Seo, D.J., and Choi, C. (2021). Antiviral Bioactive Compounds of Mushrooms and Their Antiviral Mechanisms: A Review. Viruses, 13.","DOI":"10.3390\/v13020350"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1016\/j.bmcl.2015.05.081","article-title":"Anti-influenza activities of polyphenols from the medicinal mushroom Phellinus baumii","volume":"25","author":"Hwang","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1007\/s12275-013-3384-2","article-title":"The anti-influenza virus effect of Phellinus igniarius extract","volume":"51","author":"Lee","year":"2013","journal-title":"J. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105695","DOI":"10.1016\/j.fitote.2023.105695","article-title":"Phellinus linteus mycelia extract in COVID-19 prevention and identification of its key metabolic compounds profiling using UPLC-QTOF-MS\/MS spectrometry","volume":"171","author":"Li","year":"2023","journal-title":"Fitoterapia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2003988","DOI":"10.1183\/13993003.03988-2020","article-title":"Influenza virus infection increases ACE2 expression and shedding in human small airway epithelial cells","volume":"58","author":"Schweitzer","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_10","first-page":"52421","article-title":"Influenza virus propagation in embryonated chicken eggs","volume":"97","author":"Brauer","year":"2015","journal-title":"J Vis Exp."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1021\/acsptsci.2c00119","article-title":"Modified Suberoylanilide Hydroxamic Acid Reduced Drug-Associated Immune Cell Death and Organ Damage under Lipopolysaccharide Inflammatory Challenge","volume":"5","author":"Truong","year":"2022","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rouxel, R.N., M\u00e9rour, E., Biacchesi, S., and Br\u00e9mont, M. (2016). Complete Protection against Influenza Virus H1N1 Strain A\/PR\/8\/34 Challenge in Mice Immunized with Non-Adjuvanted Novirhabdovirus Vaccines. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164245"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"85","DOI":"10.5501\/wjv.v5.i2.85","article-title":"Determination of 50% endpoint titer using a simple formula","volume":"5","author":"Ramakrishnan","year":"2016","journal-title":"World J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1128\/am.16.4.588-594.1968","article-title":"Replication and plaque assay of influenza virus in an established line of canine kidney cells","volume":"16","author":"Gaush","year":"1968","journal-title":"Appl. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nrmicro817","article-title":"Virus entry: Molecular mechanisms and biomedical applications","volume":"2","author":"Dimitrov","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_16","first-page":"S149","article-title":"Novel hemagglutinin-based influenza virus inhibitors","volume":"5","author":"Shen","year":"2013","journal-title":"J. Thorac. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"475","DOI":"10.3839\/jksabc.2011.073","article-title":"Screening of Phellinus linteus, a medicinal mushroom, for anti-viral activity","volume":"54","author":"Lee","year":"2011","journal-title":"J. Korean Soc. Appl. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hariono, M., Abdullah, N., Damodaran, K.V., Kamarulzaman, E.E., Mohamed, N., Hassan, S.S., Shamsuddin, S., and Wahab, H.A. (2016). Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay. Sci. Rep., 6.","DOI":"10.1038\/srep38692"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"189","DOI":"10.5941\/MYCO.2014.42.2.189","article-title":"Neuraminidase Inhibitors from the Fermentation Broth of Phellinus linteus","volume":"42","author":"Hwang","year":"2014","journal-title":"Mycobiology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1007\/s12250-020-00302-6","article-title":"Inhibitory Activity of Honeysuckle Extracts against Influenza A Virus In Vitro and In Vivo","volume":"36","author":"Li","year":"2021","journal-title":"Virol. Sin."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1002\/fsn3.1469","article-title":"Optimized production and safety evaluation of hispidin-enriched Sanghuangporus sanghuang mycelia","volume":"8","author":"Li","year":"2020","journal-title":"Food Sci. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jcma.2011.05.005","article-title":"Early experience of the pandemic influenza H1N1 2009 epidemic in Taiwan","volume":"74","author":"Yang","year":"2011","journal-title":"J. Chin. Med. Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13223-018-0278-1","article-title":"An introduction to immunology and immunopathology","volume":"14","author":"Marshall","year":"2018","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Guo, Z., Zhang, Z., Prajapati, M., and Li, Y. (2021). Lymphopenia Caused by Virus Infections and the Mechanisms Beyond. Viruses, 13.","DOI":"10.3390\/v13091876"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5800","DOI":"10.1172\/JCI137265","article-title":"Landscape of coordinated immune responses to H1N1 challenge in humans","volume":"130","author":"Rahil","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Frank, K., and Paust, S. (2020). Dynamic Natural Killer Cell and T Cell Responses to Influenza Infection. Front. Cell Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00425"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nri3818","article-title":"The ins and outs of MHC class II-mediated antigen processing and presentation","volume":"15","author":"Roche","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1002\/eji.1830160809","article-title":"The roles of interleukin 2 and interferon-gamma in human B cell activation, growth and differentiation","volume":"16","author":"Jelinek","year":"1986","journal-title":"Eur. J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"495848","DOI":"10.1155\/2013\/495848","article-title":"IL-1\u03b2 and IL-6 Upregulation in Children with H1N1 Influenza Virus Infection","volume":"2013","author":"Chiaretti","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_30","first-page":"2","article-title":"TNF-a, IL-1\u00df and IL-6 Levels in Pandemic Influenza A (H1N1) 2009 Patients and Effect on Mortality","volume":"2","author":"Solay","year":"2013","journal-title":"Mediterr. J. Infect. Microb. Antimicrob."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1111\/bph.16343","article-title":"AMG487 alleviates influenza A (H1N1) virus-induced pulmonary inflammation through decreasing IFN-\u03b3-producing lymphocytes and IFN-\u03b3 concentrations","volume":"181","author":"Ding","year":"2024","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e64","DOI":"10.1590\/s1678-9946202264064","article-title":"The role of IFN-\u03b3 production during retroviral infections: An important cytokine involved in chronic inflammation and pathogenesis","volume":"64","author":"Cordeiro","year":"2022","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/23\/4047\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:53:04Z","timestamp":1764154384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/23\/4047"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":32,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["foods14234047"],"URL":"https:\/\/doi.org\/10.3390\/foods14234047","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]}}}