{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:14:04Z","timestamp":1780524844216,"version":"3.54.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,12,5]],"date-time":"2016-12-05T00:00:00Z","timestamp":1480896000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,12,5]],"date-time":"2016-12-05T00:00:00Z","timestamp":1480896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To illuminate the anti-allergy mechanism of astragaloside IV (AS-IV), we assessed its effects in a murine model of allergic contact dermatitis (ACD). AS-IV administered in the sensitization phase, rather than in the elicitation phase, dramatically alleviated the symptoms of allergic inflammation. We hypothesized that AS-IV exerts its anti-allergy effects by regulating the production of key pro-allergic cytokines based on the fact that interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) levels increase significantly in the initial stage of the sensitization phase. AS-IV administered in the initial stage of ACD inhibited TSLP and IL-33 expression and reduced the proportion of type-2 innate lymphoid cells (ILC2s). An <jats:italic>in vitro<\/jats:italic> study showed that the production of pro-allergic cytokines was significantly inhibited in AS-IV presenting HaCaT cells. We also verified that AS-IV administered only in the initial stage markedly alleviated inflammation, including ear swelling, Th2 cytokine expression, and histological changes. Taken together, these results suggest that AS-IV effectively ameliorates the progression of allergic inflammation by inhibiting key initiating factors, including TSLP and IL-33, and can be used to prevent and\/or treat patients with ACD. Our data also suggest that these key pro-allergic cytokines are potential therapeutic targets for allergic diseases.<\/jats:p>","DOI":"10.1038\/srep38241","type":"journal-article","created":{"date-parts":[[2016,12,5]],"date-time":"2016-12-05T10:19:00Z","timestamp":1480933140000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Astragaloside IV ameliorates allergic inflammation by inhibiting key initiating factors in the initial stage of sensitization"],"prefix":"10.1038","volume":"6","author":[{"given":"Kai-fan","family":"Bao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-li","family":"Gui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-liang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-rong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,5]]},"reference":[{"key":"BFsrep38241_CR1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.drudis.2015.07.010","volume":"21","author":"JN Larsen","year":"2016","unstructured":"Larsen, J. N., Broge, L. & Jacobi, H. Allergy immunotherapy: the future of allergy treatment. Drug Discov Today 21, 26\u201337 (2016).","journal-title":"Drug Discov Today"},{"key":"BFsrep38241_CR2","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1183\/09031936.05.00006005","volume":"26","author":"SN Georas","year":"2005","unstructured":"Georas, S. N., Guo, J., De Fanis, U. & Casolaro, V. T-helper cell type-2 regulation in allergic disease. Eur Respir J 26, 1119\u20131137 (2005).","journal-title":"Eur Respir J"},{"key":"BFsrep38241_CR3","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.jaci.2007.07.015","volume":"120","author":"SH Sicherer","year":"2007","unstructured":"Sicherer, S. H. & Sampson, H. A. Peanut allergy: emerging concepts and approaches for an apparent epidemic. J Allergy Clin Immunol 120, 491-503; quiz 504\u2013495 (2007).","journal-title":"J Allergy Clin Immunol"},{"key":"BFsrep38241_CR4","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1067\/mai.2002.125600","volume":"110","author":"R De Marco","year":"2002","unstructured":"De Marco, R. et al. Incidence and remission of asthma: a retrospective study on the natural history of asthma in Italy. J Allergy Clin Immunol 110, 228\u2013235 (2002).","journal-title":"J Allergy Clin Immunol"},{"key":"BFsrep38241_CR5","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3109\/02770903.2011.637594","volume":"49","author":"RA Winer","year":"2012","unstructured":"Winer, R. A., Qin, X., Harrington, T., Moorman, J. & Zahran, H. Asthma incidence among children and adults: findings from the Behavioral Risk Factor Surveillance system asthma call-back survey\u2013United States, 2006-2008. The Journal of asthma : official journal of the Association for the Care of Asthma 49, 16\u201322 (2012).","journal-title":"The Journal of asthma : official journal of the Association for the Care of Asthma"},{"key":"BFsrep38241_CR6","doi-asserted-by":"publisher","first-page":"587","DOI":"10.2340\/00015555-2051","volume":"95","author":"U Akerstrom","year":"2015","unstructured":"Akerstrom, U. et al. Comparison of Moisturizing Creams for the Prevention of Atopic Dermatitis Relapse: A Randomized Double-blind Controlled Multicentre Clinical Trial. Acta dermato-venereologica 95, 587\u2013592 (2015).","journal-title":"Acta dermato-venereologica"},{"key":"BFsrep38241_CR7","first-page":"1346","volume":"31","author":"JY Han","year":"2011","unstructured":"Han, J. Y. & Cui, J. P. [Effect of biantong huangqi ointment combined with western medicine on the recurrence of children\u2019s bronchial asthma]. Zhongguo Zhong xi yi jie he za zhi 31, 1346\u20131348 (2011).","journal-title":"Zhongguo Zhong xi yi jie he za zhi"},{"key":"BFsrep38241_CR8","doi-asserted-by":"crossref","unstructured":"Feng, M., Yuan, W., Zhang, R., Fu, P. & Wu, T. Chinese herbal medicine Huangqi type formulations for nephrotic syndrome. The Cochrane database of systematic reviews 6, CD006335 (2013).","DOI":"10.1002\/14651858.CD006335.pub3"},{"key":"BFsrep38241_CR9","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1002\/ptr.3062","volume":"24","author":"Z Matkovic","year":"2010","unstructured":"Matkovic, Z. et al. Efficacy and safety of Astragalus membranaceus in the treatment of patients with seasonal allergic rhinitis. Phytotherapy research: PTR 24, 175\u2013181 (2010).","journal-title":"Phytotherapy research: PTR"},{"key":"BFsrep38241_CR10","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.imbio.2014.03.005","volume":"219","author":"X Huang","year":"2014","unstructured":"Huang, X., Tang, L., Wang, F. & Song, G. Astragaloside IV attenuates allergic inflammation by regulation Th1\/Th2 cytokine and enhancement CD4(+)CD25(+)Foxp3 T cells in ovalbumin-induced asthma. Immunobiology 219, 565\u2013571 (2014).","journal-title":"Immunobiology"},{"key":"BFsrep38241_CR11","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.immuni.2015.07.007","volume":"43","author":"H Hammad","year":"2015","unstructured":"Hammad, H. & Lambrecht, B. N. Barrier Epithelial Cells and the Control of Type 2 Immunity. Immunity 43, 29\u201340 (2015).","journal-title":"Immunity"},{"key":"BFsrep38241_CR12","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1038\/nature13577","volume":"513","author":"C Schiering","year":"2014","unstructured":"Schiering, C. et al. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 513, 564\u2013568 (2014).","journal-title":"Nature"},{"key":"BFsrep38241_CR13","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.coi.2014.09.004","volume":"31","author":"C Cayrol","year":"2014","unstructured":"Cayrol, C. & Girard, J. P. IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy. Curr Opin Immunol 31, 31\u201337 (2014).","journal-title":"Curr Opin Immunol"},{"key":"BFsrep38241_CR14","doi-asserted-by":"publisher","first-page":"2939","DOI":"10.1084\/jem.20130351","volume":"210","author":"M Salimi","year":"2013","unstructured":"Salimi, M. et al. A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. J Exp Med 210, 2939\u20132950 (2013).","journal-title":"J Exp Med"},{"key":"BFsrep38241_CR15","doi-asserted-by":"publisher","first-page":"5094","DOI":"10.4049\/jimmunol.0802387","volume":"183","author":"D Prefontaine","year":"2009","unstructured":"Prefontaine, D. et al. Increased expression of IL-33 in severe asthma: evidence of expression by airway smooth muscle cells. J Immunol 183, 5094\u20135103 (2009).","journal-title":"J Immunol"},{"key":"BFsrep38241_CR16","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/j.jaci.2009.12.935","volume":"125","author":"D Prefontaine","year":"2010","unstructured":"Prefontaine, D. et al. Increased IL-33 expression by epithelial cells in bronchial asthma. J Allergy Clin Immunol 125, 752\u2013754 (2010).","journal-title":"J Allergy Clin Immunol"},{"key":"BFsrep38241_CR17","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/nature11714","volume":"493","author":"IJ Juncadella","year":"2013","unstructured":"Juncadella, I. J. et al. Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation. Nature 493, 547\u2013551 (2013).","journal-title":"Nature"},{"key":"BFsrep38241_CR18","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1084\/jem.20051745","volume":"203","author":"YJ Liu","year":"2006","unstructured":"Liu, Y. J. Thymic stromal lymphopoietin: master switch for allergic inflammation. J Exp Med 203, 269\u2013273 (2006).","journal-title":"J Exp Med"},{"key":"BFsrep38241_CR19","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.1002\/eji.201041195","volume":"41","author":"M Kitajima","year":"2011","unstructured":"Kitajima, M., Lee, H. C., Nakayama, T. & Ziegler, S. F. TSLP enhances the function of helper type 2 cells. European journal of immunology 41, 1862\u20131871 (2011).","journal-title":"European journal of immunology"},{"key":"BFsrep38241_CR20","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1038\/mi.2009.134","volume":"3","author":"MR Comeau","year":"2010","unstructured":"Comeau, M. R. & Ziegler, S. F. The influence of TSLP on the allergic response. Mucosal immunology 3, 138\u2013147 (2010).","journal-title":"Mucosal immunology"},{"key":"BFsrep38241_CR21","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1586\/1744666X.2014.967684","volume":"10","author":"A Cianferoni","year":"2014","unstructured":"Cianferoni, A. & Spergel, J. The importance of TSLP in allergic disease and its role as a potential therapeutic target. Expert Rev Clin Immunol 10, 1463\u20131474 (2014).","journal-title":"Expert Rev Clin Immunol"},{"key":"BFsrep38241_CR22","doi-asserted-by":"publisher","first-page":"27","DOI":"10.2332\/allergolint.11-RAI-0374","volume":"61","author":"M Omori-Miyake","year":"2012","unstructured":"Omori-Miyake, M. & Ziegler, S. F. Mouse models of allergic diseases: TSLP and its functional roles. Allergol Int 61, 27\u201334 (2012).","journal-title":"Allergol Int"},{"key":"BFsrep38241_CR23","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1084\/jem.20041503","volume":"202","author":"J Yoo","year":"2005","unstructured":"Yoo, J. et al. Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin. J Exp Med 202, 541\u2013549 (2005).","journal-title":"J Exp Med"},{"key":"BFsrep38241_CR24","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/76923","volume":"1","author":"A Pandey","year":"2000","unstructured":"Pandey, A. et al. Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Nat Immunol 1, 59\u201364 (2000).","journal-title":"Nat Immunol"},{"key":"BFsrep38241_CR25","doi-asserted-by":"publisher","first-page":"8183","DOI":"10.4049\/jimmunol.174.12.8183","volume":"174","author":"S Ying","year":"2005","unstructured":"Ying, S. et al. Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J Immunol 174, 8183\u20138190 (2005).","journal-title":"J Immunol"},{"key":"BFsrep38241_CR26","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.4049\/jimmunol.0803478","volume":"184","author":"RP Larson","year":"2010","unstructured":"Larson, R. P. et al. Dibutyl phthalate-induced thymic stromal lymphopoietin is required for Th2 contact hypersensitivity responses. J Immunol 184, 2974\u20132984 (2010).","journal-title":"J Immunol"},{"key":"BFsrep38241_CR27","first-page":"428","volume":"23","author":"K Taniguchi","year":"2013","unstructured":"Taniguchi, K. et al. Interleukin 33 is induced by tumor necrosis factor alpha and interferon gamma in keratinocytes and contributes to allergic contact dermatitis. J Investig Allergol Clin Immunol 23, 428\u2013434 (2013).","journal-title":"J Investig Allergol Clin Immunol"},{"key":"BFsrep38241_CR28","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/ni805","volume":"3","author":"V Soumelis","year":"2002","unstructured":"Soumelis, V. et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol 3, 673\u2013680 (2002).","journal-title":"Nat Immunol"},{"key":"BFsrep38241_CR29","doi-asserted-by":"crossref","unstructured":"Shelfoon, C. et al. Chemokine release from human rhinovirus-infected airway epithelial cells promotes fibroblast migration. J Allergy Clin Immunol (2016).","DOI":"10.1016\/j.jaci.2015.12.1308"},{"key":"BFsrep38241_CR30","doi-asserted-by":"crossref","unstructured":"Steelant, B. et al. Impaired barrier function in patients with house dust mite-induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression. J Allergy Clin Immunol (2016).","DOI":"10.1016\/j.jaci.2015.10.050"},{"key":"BFsrep38241_CR31","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1126\/science.1106442","volume":"307","author":"TT Macdonald","year":"2005","unstructured":"Macdonald, T. T. & Monteleone, G. Immunity, inflammation, and allergy in the gut. Science 307, 1920\u20131925 (2005).","journal-title":"Science"},{"key":"BFsrep38241_CR32","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1016\/j.jaci.2007.08.046","volume":"120","author":"RP Schleimer","year":"2007","unstructured":"Schleimer, R. P., Kato, A., Kern, R., Kuperman, D. & Avila, P. C. Epithelium: at the interface of innate and adaptive immune responses. J Allergy Clin Immunol 120, 1279\u20131284 (2007).","journal-title":"J Allergy Clin Immunol"},{"key":"BFsrep38241_CR33","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1038\/ni.2617","volume":"14","author":"P Licona-Limon","year":"2013","unstructured":"Licona-Limon, P., Kim, L. K., Palm, N. W. & Flavell, R. A. TH2, allergy and group 2 innate lymphoid cells. Nat Immunol 14, 536\u2013542 (2013).","journal-title":"Nat Immunol"},{"key":"BFsrep38241_CR34","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1111\/all.12004","volume":"67","author":"T Ohno","year":"2012","unstructured":"Ohno, T., Morita, H., Arae, K., Matsumoto, K. & Nakae, S. Interleukin-33 in allergy. Allergy 67, 1203\u20131214 (2012).","journal-title":"Allergy"},{"key":"BFsrep38241_CR35","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/exd.12311","volume":"23","author":"M Worm","year":"2014","unstructured":"Worm, M. Allergic contact dermatitis beyond IL-1beta role of additional family members. Exp Dermatol 23, 151\u2013152 (2014).","journal-title":"Exp Dermatol"},{"key":"BFsrep38241_CR36","doi-asserted-by":"crossref","unstructured":"Galand, C. et al. IL-33 promotes food anaphylaxis in epicutaneously sensitized mice by targeting mast cells. J Allergy Clin Immunol (2016).","DOI":"10.1016\/j.jaci.2015.12.620"},{"key":"BFsrep38241_CR37","doi-asserted-by":"publisher","first-page":"e1000067","DOI":"10.1371\/journal.pbio.1000067","volume":"7","author":"S Demehri","year":"2009","unstructured":"Demehri, S., Morimoto, M., Holtzman, M. J. & Kopan, R. Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma. PLoS biology 7, e1000067 (2009).","journal-title":"PLoS biology"},{"key":"BFsrep38241_CR38","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1073\/pnas.0812668106","volume":"106","author":"Z Zhang","year":"2009","unstructured":"Zhang, Z. et al. Thymic stromal lymphopoietin overproduced by keratinocytes in mouse skin aggravates experimental asthma. Proceedings of the National Academy of Sciences of the United States of America 106, 1536\u20131541 (2009).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep38241_CR39","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.immuni.2014.01.011","volume":"40","author":"TY Halim","year":"2014","unstructured":"Halim, T. Y. et al. Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. Immunity 40, 425\u2013435 (2014).","journal-title":"Immunity"},{"key":"BFsrep38241_CR40","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402\u2013408 (2001).","journal-title":"Methods"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep38241.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep38241","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep38241.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T01:18:41Z","timestamp":1672881521000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep38241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,5]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep38241"],"URL":"https:\/\/doi.org\/10.1038\/srep38241","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,5]]},"assertion":[{"value":"20 July 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"38241"}}