{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T17:58:14Z","timestamp":1793210294140,"version":"4.5.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82074133"],"award-info":[{"award-number":["82074133"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003453","name":"the Natural Science Foundation of Guangdong","doi-asserted-by":"crossref","award":["2019A1515011071"],"award-info":[{"award-number":["2019A1515011071"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the National science and technology major projects of China","award":["2014ZX10003002-003-002"],"award-info":[{"award-number":["2014ZX10003002-003-002"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Complement Med Ther"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Influenza A virus infection due to drug resistance and side effects of the conventional antiviral drugs yet remains a serious public health threat for humans and animals. Forsythiaside A is an effective ingredient isolated from the Chinese herbal medicine forsythia. It has various pharmacological effects and has a good therapeutic effect against a variety of infectious diseases. This study aimed to further explore the immunological mechanism of Forsythiaside A in the treatment of influenza virus-infected mice and its effect on the Toll-like receptor 7 (TLR7) signaling pathway in the lungs of these mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      C57\/BL6J mice and TLR7\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice were infected with the FM1 strains (H1N1 and A\/FM\/1\/4) of the Influenza A virus. Each group of experimental mice were divided into the mock, virus, oseltamivir, and Forsythiaside A groups. Weight change, lung index change, and the mRNA and protein expression levels of key factors in the TLR7 signaling pathway were detected. Flow cytometry was used to detect the changes in the Th1\/Th2 and Th17\/Treg ratios.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After infection with the Influenza A virus, the weight loss of C57\/BL6J mice treated with forsythoside A and oseltamivir decreased, and the pathological tissue sections showed that the inflammatory damage was reduced. The expression levels of the key factors, TLR7, myeloid differentiation factor 88(Myd88), and nuclear factor-kappa B (NF-\u03baB) in the TLR7 signaling pathway were significantly reduced. Flow cytometry showed that Th1\/Th2 and Th17\/Treg ratios decreased after Forsythiaside A treatment. In the TLR7\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, there was no significant change after Forsythiaside A treatment in the virus group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Forsythiaside A affects the TLR7 signaling pathway in mouse lung immune cells and reduces the inflammatory response caused by the Influenza A virus FM1 strain in mouse lungs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12906-022-03644-8","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T03:04:11Z","timestamp":1655867051000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Forsythiaside A improves Influenza A virus infection through TLR7 signaling pathway in the lungs of mice"],"prefix":"10.1186","volume":"22","author":[{"given":"Xiao","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyou","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"issue":"2","key":"3644_CR1","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1211\/jpp.60.2.0016","volume":"60","author":"H Qu","year":"2008","unstructured":"Qu H, Zhang Y, Wang Y, Li B, Sun W. Antioxidant and antibacterial activity of two compounds (forsythiaside and forsythin) isolated from Forsythia suspensa. J Pharm Pharmacol. 2008;60(2):261\u20136.","journal-title":"J Pharm Pharmacol"},{"key":"3644_CR2","doi-asserted-by":"publisher","first-page":"105690","DOI":"10.1016\/j.phrs.2021.105690","volume":"169","author":"L Gong","year":"2021","unstructured":"Gong L, Wang C, Zhou H, Ma C, Zhang Y, Peng C, Li Y. A review of pharmacological and pharmacokinetic properties of Forsythiaside A. Pharmacol Res. 2021;169:105690.","journal-title":"Pharmacol Res"},{"key":"3644_CR3","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1248\/cpb.30.1048","volume":"30","author":"S Nishibe","year":"1982","unstructured":"Nishibe S, Okabe K, Tsukamoto H, Sakushima A, Hisada S. The structure of Forsythiaside isolated from Forsythia suspensa. Chem Pharm Bull. 1982;30:1048\u201350.","journal-title":"Chem Pharm Bull"},{"issue":"4","key":"3644_CR4","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/s11064-015-1731-x","volume":"41","author":"Y Wang","year":"2016","unstructured":"Wang Y, Zhao H, Lin C, Ren J, Zhang S. Forsythiaside A exhibits anti-inflammatory effects in LPS-stimulated BV2 microglia cells through activation of Nrf2\/HO-1 signaling pathway. Neurochem Res. 2016;41(4):659\u201365.","journal-title":"Neurochem Res"},{"issue":"1","key":"3644_CR5","doi-asserted-by":"publisher","first-page":"243","DOI":"10.3892\/ijmm.2017.2990","volume":"40","author":"XY Zeng","year":"2017","unstructured":"Zeng XY, Yuan W, Zhou L, Wang SX, Xie Y, Fu YJ. Forsythoside A exerts an anti-endotoxin effect by blocking the LPS\/TLR4 signaling pathway and inhibiting Tregs in vitro. Int J Mol Med. 2017;40(1):243\u201350.","journal-title":"Int J Mol Med"},{"key":"3644_CR6","doi-asserted-by":"publisher","first-page":"108466","DOI":"10.1016\/j.intimp.2021.108466","volume":"103","author":"W Lang","year":"2022","unstructured":"Lang W, Cheng M, Zheng X, Zhao Y, Qu Y, Jia Z, Gong H, Ali I, Tang J, Zhang H. Forsythiaside A alleviates methotrexate-induced intestinal mucositis in rats by modulating the NLRP3 signaling pathways. Int Immunopharmacol. 2022;103:108466.","journal-title":"Int Immunopharmacol"},{"key":"3644_CR7","first-page":"9938392","volume":"2022","author":"M Zhou","year":"2022","unstructured":"Zhou M, Zhao X, Liao L, Deng Y, Liu M, Wang J, Xue X, Li Y. Forsythiaside A regulates activation of hepatic stellate cells by inhibiting NOX4-dependent ROS. Oxid Med Cell Longev. 2022;2022:9938392.","journal-title":"Oxid Med Cell Longev"},{"issue":"3","key":"3644_CR8","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1002\/ptr.3260","volume":"25","author":"H Li","year":"2011","unstructured":"Li H, Wu J, Zhang Z, Ma Y, Liao F, Zhang Y, Wu G. Forsythoside a inhibits the avian infectious bronchitis virus in cell culture. Phytother Res. 2011;25(3):338\u201342.","journal-title":"Phytother Res"},{"issue":"8","key":"3644_CR9","doi-asserted-by":"publisher","first-page":"223","DOI":"10.3390\/v9080223","volume":"9","author":"JM Shim","year":"2017","unstructured":"Shim JM, Kim J, Tenson T, Min JY, Kainov DE. Influenza virus infection, interferon response, viral counter-response, and apoptosis. Viruses. 2017;9(8):223.","journal-title":"Viruses"},{"issue":"1","key":"3644_CR10","doi-asserted-by":"publisher","first-page":"3422","DOI":"10.1038\/s41467-019-11249-y","volume":"10","author":"BM Tang","year":"2019","unstructured":"Tang BM, Shojaei M, Teoh S, Meyers A, Ho J, Ball TB, Keynan Y, Pisipati A, Kumar A, Eisen DP, et al. Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection. Nat Commun. 2019;10(1):3422.","journal-title":"Nat Commun"},{"issue":"4","key":"3644_CR11","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.bbrc.2019.03.113","volume":"512","author":"Y Zhu","year":"2019","unstructured":"Zhu Y, Shao Y, Qu X, Guo J, Yang J, Zhou Z, Wang S. Sodium ferulate protects against influenza virus infection by activation of the TLR7\/9-MyD88-IRF7 signaling pathway and inhibition of the NF-kappaB signaling pathway. Biochem Biophys Res Commun. 2019;512(4):793\u20138.","journal-title":"Biochem Biophys Res Commun"},{"issue":"12","key":"3644_CR12","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1002\/ptr.6196","volume":"32","author":"YQ Yan","year":"2018","unstructured":"Yan YQ, Fu YJ, Wu S, Qin HQ, Zhen X, Song BM, Weng YS, Wang PC, Chen XY, Jiang ZY. Anti-influenza activity of berberine improves prognosis by reducing viral replication in mice. Phytother Res. 2018;32(12):2560\u20137.","journal-title":"Phytother Res"},{"issue":"6","key":"3644_CR13","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1089\/vim.2016.0178","volume":"30","author":"M Okamoto","year":"2017","unstructured":"Okamoto M, Tsukamoto H, Kouwaki T, Seya T, Oshiumi H. Recognition of viral RNA by pattern recognition receptors in the induction of innate immunity and excessive inflammation during respiratory viral infections. Viral Immunol. 2017;30(6):408\u201320.","journal-title":"Viral Immunol"},{"issue":"5","key":"3644_CR14","doi-asserted-by":"publisher","first-page":"524","DOI":"10.3390\/molecules21050524","volume":"21","author":"L Deng","year":"2016","unstructured":"Deng L, Pang P, Zheng K, Nie J, Xu H, Wu S, Chen J, Chen X. Forsythoside A controls influenza A virus infection and improves the prognosis by inhibiting virus replication in mice. Molecules. 2016;21(5):524.","journal-title":"Molecules"},{"issue":"5","key":"3644_CR15","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1017\/S0950268813002689","volume":"142","author":"C Panayiotou","year":"2014","unstructured":"Panayiotou C, Richter J, Bashiardes S, Koptides D, Tryfonos C, Christodoulou C. Molecular epidemiology of influenza A virus infection in Cyprus in four consecutive seasons (2009 pandemic-2013). Epidemiol Infect. 2014;142(5):975\u201383.","journal-title":"Epidemiol Infect"},{"key":"3644_CR16","doi-asserted-by":"publisher","first-page":"14171","DOI":"10.1038\/srep14171","volume":"5","author":"M Liu","year":"2015","unstructured":"Liu M, Zhao X, Hua S, Du X, Peng Y, Li X, Lan Y, Wang D, Wu A, Shu Y, et al. Antigenic patterns and evolution of the human influenza A (H1N1) virus. Sci Rep. 2015;5:14171.","journal-title":"Sci Rep"},{"issue":"9","key":"3644_CR17","doi-asserted-by":"publisher","first-page":"e2020495","DOI":"10.1001\/jamanetworkopen.2020.20495","volume":"3","author":"X Song","year":"2020","unstructured":"Song X, Delaney M, Shah RK, Campos JM, Wessel DL, DeBiasi RL. Comparison of clinical features of COVID-19 vs seasonal influenza A and B in US children. JAMA Netw Open. 2020;3(9):e2020495.","journal-title":"JAMA Netw Open"},{"issue":"1","key":"3644_CR18","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.intimp.2015.07.011","volume":"28","author":"L Cheng","year":"2015","unstructured":"Cheng L, Li F, Ma R, Hu X. Forsythiaside inhibits cigarette smoke-induced lung inflammation by activation of Nrf2 and inhibition of NF-kappaB. Int Immunopharmacol. 2015;28(1):494\u20139.","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"3644_CR19","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/s12974-020-01855-9","volume":"17","author":"L Gong","year":"2020","unstructured":"Gong L, Yu L, Gong X, Wang C, Hu N, Dai X, Peng C, Li Y. Exploration of anti-inflammatory mechanism of forsythiaside A and forsythiaside B in CuSO4-induced inflammation in zebrafish by metabolomic and proteomic analyses. J Neuroinflammation. 2020;17(1):173.","journal-title":"J Neuroinflammation"},{"issue":"9","key":"3644_CR20","doi-asserted-by":"publisher","first-page":"e0162791","DOI":"10.1371\/journal.pone.0162791","volume":"11","author":"QJ Song","year":"2016","unstructured":"Song QJ, Weng XG, Cai DJ, Zhang W, Wang JF. Forsythoside A inhibits BVDV replication via TRAF2-dependent CD28-4-1BB signaling in bovine PBMCs. PLoS One. 2016;11(9):e0162791.","journal-title":"PLoS One"},{"issue":"23","key":"3644_CR21","doi-asserted-by":"publisher","first-page":"4219","DOI":"10.3390\/molecules24234219","volume":"24","author":"X Zheng","year":"2019","unstructured":"Zheng X, Fu Y, Shi SS, Wu S, Yan Y, Xu L, Wang Y, Jiang Z. Effect of Forsythiaside A on the RLRs signaling pathway in the lungs of mice infected with the influenza A Virus FM1 strain. Molecules. 2019;24(23):4219.","journal-title":"Molecules"},{"issue":"9","key":"3644_CR22","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.3390\/molecules22091466","volume":"22","author":"Z Dong","year":"2017","unstructured":"Dong Z, Lu X, Tong X, Dong Y, Tang L, Liu M. Forsythiae Fructus: a review on its phytochemistry, quality control, pharmacology and pharmacokinetics. Molecules. 2017;22(9):1466.","journal-title":"Molecules"},{"issue":"9979","key":"3644_CR23","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1016\/S0140-6736(15)60074-5","volume":"385","author":"H Kelly","year":"2015","unstructured":"Kelly H, Cowling BJ. Influenza: the rational use of oseltamivir. Lancet. 2015;385(9979):1700\u20132.","journal-title":"Lancet"},{"issue":"1","key":"3644_CR24","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.bj.2018.12.009","volume":"42","author":"C Biondo","year":"2019","unstructured":"Biondo C, Lentini G, Beninati C, Teti G. The dual role of innate immunity during influenza. Biomed J. 2019;42(1):8\u201318.","journal-title":"Biomed J"},{"issue":"2","key":"3644_CR25","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1111\/imm.12373","volume":"144","author":"SH Yeon","year":"2015","unstructured":"Yeon SH, Song MJ, Kang HR, Lee JY. Phosphatidylinositol-3-kinase and Akt are required for RIG-I-mediated anti-viral signalling through cross-talk with IPS-1. Immunology. 2015;144(2):312\u201320.","journal-title":"Immunology"},{"issue":"5","key":"3644_CR26","doi-asserted-by":"publisher","first-page":"e1004134","DOI":"10.1371\/journal.ppat.1004134","volume":"10","author":"L Kedzierski","year":"2014","unstructured":"Kedzierski L, Linossi EM, Kolesnik TB, Day EB, Bird NL, Kile BT, Belz GT, Metcalf D, Nicola NA, Kedzierska K, et al. Suppressor of cytokine signaling 4 (SOCS4) protects against severe cytokine storm and enhances viral clearance during influenza infection. PLoS Pathog. 2014;10(5):e1004134.","journal-title":"PLoS Pathog"},{"issue":"3","key":"3644_CR27","doi-asserted-by":"publisher","first-page":"a032102","DOI":"10.1101\/cshperspect.a032102","volume":"10","author":"S Crotty","year":"2018","unstructured":"Crotty S. Do memory CD4 T cells keep their cell-type programming: plasticity versus fate commitment? Complexities of interpretation due to the heterogeneity of memory CD4 T cells, including T follicular helper cells. Cold Spring Harb Perspect Biol. 2018;10(3):a032102.","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"3644_CR28","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.brainres.2014.09.076","volume":"1592","author":"Y Xia","year":"2014","unstructured":"Xia Y, Qi F, Zou J, Yao Z. Influenza A(H1N1) vaccination during early pregnancy transiently promotes hippocampal neurogenesis and working memory. Involvement of Th1\/Th2 balance. Brain Res. 2014;1592:34\u201343.","journal-title":"Brain Res"},{"key":"3644_CR29","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1007\/978-94-017-9487-9_9","volume":"841","author":"Y Zhang","year":"2014","unstructured":"Zhang Y, Zhang Y, Gu W, Sun B. Erratum to: Th1\/Th2 cell differentiation and molecular signals. Adv Exp Med Biol. 2014;841:E1-2.","journal-title":"Adv Exp Med Biol"},{"issue":"3","key":"3644_CR30","doi-asserted-by":"publisher","first-page":"730","DOI":"10.3390\/ijms19030730","volume":"19","author":"GR Lee","year":"2018","unstructured":"Lee GR. The balance of Th17 versus Treg cells in autoimmunity. Int J Mol Sci. 2018;19(3):730.","journal-title":"Int J Mol Sci"},{"issue":"2","key":"3644_CR31","first-page":"1313","volume":"20","author":"T Ma","year":"2019","unstructured":"Ma T, Shi YL, Wang YL. Forsythiaside A protects against focal cerebral ischemic injury by mediating the activation of the Nrf2 and endoplasmic reticulum stress pathways. Mol Med Rep. 2019;20(2):1313\u201320.","journal-title":"Mol Med Rep"},{"key":"3644_CR32","doi-asserted-by":"publisher","first-page":"112563","DOI":"10.1016\/j.ejmech.2020.112563","volume":"209","author":"XY Tian","year":"2021","unstructured":"Tian XY, Li MX, Lin T, Qiu Y, Zhu YT, Li XL, Tao WD, Wang P, Ren XX, Chen LP. A review on the structure and pharmacological activity of phenylethanoid glycosides. Eur J Med Chem. 2021;209:112563.","journal-title":"Eur J Med Chem"}],"container-title":["BMC Complementary Medicine and Therapies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-022-03644-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12906-022-03644-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-022-03644-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T03:06:15Z","timestamp":1655867175000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccomplementalternmed.biomedcentral.com\/articles\/10.1186\/s12906-022-03644-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,22]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["3644"],"URL":"https:\/\/doi.org\/10.1186\/s12906-022-03644-8","relation":{},"ISSN":["2662-7671"],"issn-type":[{"value":"2662-7671","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,22]]},"assertion":[{"value":"15 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All of the animal procedures were performed in accordance with the Guidelines for Care and Use of Laboratory Animals of the Jinan University. The experiment was conducted under the supervision and evaluation of the Experimental Animal Ethics Committee of Jinan University (IACUC-20191120\u201306). The study was carried out in compliance with the ARRIVE guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"164"}}