{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:42:20Z","timestamp":1789072940336,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82004034"],"award-info":[{"award-number":["82004034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82004155"],"award-info":[{"award-number":["82004155"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M652987"],"award-info":[{"award-number":["2019M652987"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pyrogallol, a natural polyphenol compound (1,2,3\u2010trihydroxybenzene), has shown efficacy in the therapeutic treatment of disorders associated with inflammation. Nevertheless, the mechanisms underlying the protective properties of pyrogallol against influenza A virus infection are not yet established. We established in this study that pyrogallol effectively alleviated H1N1 influenza A virus\u2010induced lung injury and reduced mortality. Treatment with pyrogallol was found to promote the expression and nuclear translocation of nuclear factor erythroid\u20102\u2010related factor 2 (Nrf2) and peroxisome proliferator\u2010activated receptor gamma (PPAR\u2010\u03b3). Notably, the activation of Nrf2 by pyrogallol was involved in elevating the expression of PPAR\u2010\u03b3, both of which act synergistically to enhance heme oxygenase\u20101 (HO\u20101) synthesis. Blocking HO\u20101 by zinc protoporphyrin (ZnPP) reduced the suppressive impact of pyrogallol on H1N1 virus\u2010mediated aberrant retinoic acid\u2010inducible gene\u2010I\u2010nuclear factor kappa B (RIG\u2010I\u2013NF\u2010\u03baB) signaling, which thus abolished the dampening effects of pyrogallol on excessive proinflammatory mediators and cell death (including apoptosis, necrosis, and ferroptosis). Furthermore, the HO\u20101\u2010independent inactivation\u00a0of janus kinase 1\/signal transducers and activators of transcription (JAK1\/STATs) and the HO\u20101\u2010dependent RIG\u2010I\u2010augmented STAT1\/2 activation were both abrogated\u00a0by pyrogallol, resulting in suppression of the enhanced transcriptional activity of interferon\u2010stimulated gene factor 3 (ISGF3) complexes, thus prominently inhibiting the amplification of the H1N1 virus\u2010induced proinflammatory reaction and apoptosis in interferon\u2010beta (IFN\u2010\u03b2)\u2010sensitized cells. The study provides evidence that pyrogallol alleviates excessive proinflammatory responses and abnormal cell death via HO\u20101 induction, suggesting it could be a potential agent for treating influenza.<\/jats:p>","DOI":"10.1002\/mco2.531","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T18:09:23Z","timestamp":1712945363000},"source":"Crossref","is-referenced-by-count":18,"title":["Pyrogallol protects against influenza A virus\u2010triggered lethal lung injury by activating the Nrf2\u2013PPAR\u2010\u03b3\u2013HO\u20101 signaling axis"],"prefix":"10.1002","volume":"5","author":[{"given":"Beixian","family":"Zhou","sequence":"first","affiliation":[{"name":"The People's Hospital of Gaozhou  Gaozhou China"},{"name":"Cancer Center, Integrated Hospital of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangzhou Laboratory  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushan","family":"Yang","sequence":"additional","affiliation":[{"name":"The People's Hospital of Gaozhou  Gaozhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyun","family":"Liang","sequence":"additional","affiliation":[{"name":"The People's Hospital of Gaozhou  Gaozhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The People's Hospital of Gaozhou  Gaozhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanyu","family":"Liu","sequence":"additional","affiliation":[{"name":"The People's Hospital of Gaozhou  Gaozhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiping","family":"Pan","sequence":"additional","affiliation":[{"name":"Guangzhou Laboratory  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease National Clinical Research Center of Respiratory Disease Guangzhou Institute of Respiratory Health Institute of Chinese Integrative Medicine Guangdong\u2010Hongkong\u2010Macao Joint Laboratory of Infectious Respiratory Disease the First Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)33293-2"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01439-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007428"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711942105"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2021.149719"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-019-01311-2"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2009.01.016"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.proche.2016.01.025"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20163985"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.08.030"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.24099"},{"issue":"6","key":"e_1_2_10_13_1","first-page":"721","article-title":"Pyrogallol as a glutathione depletor induces apoptosis in HeLa cells","volume":"21","author":"Han YH","year":"2008","journal-title":"Int J Mol Med"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20369"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.25.19"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23751-3"},{"key":"e_1_2_10_17_1","first-page":"662","article-title":"Host and viral modulation of RIG\u2010I\u2010mediated antiviral immunity","volume":"7","author":"Liu Y","year":"2016","journal-title":"Front Immunol"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2018.12.014"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005754"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00845-15"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2015.74"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6808934"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir665"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03047"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004048"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2007.06.009"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4864"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003188"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-020-0403-9"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2019.09.005"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200907-1047OC"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1378175"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2019.0032"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103378"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3512"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019059108"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00766"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2017.12.18"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.04.027"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-021-03462-4"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0331TR"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00458.2004"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.01.007"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00338.2014"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2011.10.017"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI137468"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.03.019"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1807-59322010001200003"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403258200"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.04.007"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208419200"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01369-2"},{"issue":"17","key":"e_1_2_10_53_1","first-page":"5299","article-title":"Stat1\u2010dependent induction of tumor necrosis factor\u2010related apoptosis\u2010inducing ligand and the cell\u2010surface death signaling pathway by interferon beta in human cancer cells","volume":"63","author":"Choi EA","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2008.07.012"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-3-63"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-024-02289-y"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200607-1005OC"}],"container-title":["MedComm"],"original-title":[],"language":"it","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.531","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T16:50:54Z","timestamp":1724172654000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mco2.531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":56,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/mco2.531"],"URL":"https:\/\/doi.org\/10.1002\/mco2.531","archive":["Portico"],"relation":{},"ISSN":["2688-2663","2688-2663"],"issn-type":[{"value":"2688-2663","type":"print"},{"value":"2688-2663","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]},"article-number":"e531"}}