{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T18:03:56Z","timestamp":1778695436923,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T00:00:00Z","timestamp":1508284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.81374040"],"award-info":[{"award-number":["No.81374040"]}],"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":["No.81773976"],"award-info":[{"award-number":["No.81773976"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Education, Guangdong Government under the Top-tier University Development Scheme for Research and Control of Infectious Diseases","award":["No.2015014"],"award-info":[{"award-number":["No.2015014"]}]},{"name":"Department of Education, Guangdong Government under the Top-tier University Development Scheme for Research and Control of Infectious Diseases","award":["No. 2015087"],"award-info":[{"award-number":["No. 2015087"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Lasting activations of toll-like receptors (TLRs), MAPK and NF-\u03baB pathways can support influenza A virus (IAV) infection and promote pneumonia. In this study, we have investigated the effect and mechanism of action of emodin on IAV infection using qRT-PCR, western blotting, ELISA, Nrf2 luciferase reporter, siRNA and plaque inhibition assays. The results showed that emodin could significantly inhibit IAV (ST169, H1N1) replication, reduce IAV-induced expressions of TLR2\/3\/4\/7, MyD88 and TRAF6, decrease IAV-induced phosphorylations of p38\/JNK MAPK and nuclear translocation of NF-\u03baB p65. Emodin also activated the Nrf2 pathway, decreased ROS levels, increased GSH levelss and GSH\/GSSG ratio, and upregulated the activities of SOD, GR, CAT and GSH-Px after IAV infection. Suppression of Nrf2 via siRNA markedly blocked the inhibitory effects of emodin on IAV-induced activations of TLR4, p38\/JNK, and NF-\u03baB pathways and on IAV-induced production of IL-1\u03b2, IL-6 and expression of IAV M2 protein. Emodin also dramatically increased the survival rate of mice, reduced lung edema, pulmonary viral titer and inflammatory cytokines, and improved lung histopathological changes. In conclusion, emodin can inhibit IAV replication and influenza viral pneumonia, at least in part, by activating Nrf2 signaling and inhibiting IAV-induced activations of the TLR4, p38\/JNK MAPK and NF-\u03baB pathways.<\/jats:p>","DOI":"10.3390\/molecules22101754","type":"journal-article","created":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T11:10:00Z","timestamp":1508325000000},"page":"1754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Emodin Inhibition of Influenza A Virus Replication and Influenza Viral Pneumonia via the Nrf2, TLR4, p38\/JNK and NF-kappaB Pathways"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8304-8207","authenticated-orcid":false,"given":"Jian-Ping","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian-Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Ming","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Xua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Zhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge-Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang-Sheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1186\/1743-422X-8-280","article-title":"Molecular epidemiology of novel swine origin influenza virus (s-oiv) from Gwalior, India, 2009","volume":"8","author":"Sharma","year":"2011","journal-title":"Virol. 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