{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:08:52Z","timestamp":1791083332456,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014189","name":"Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET)","doi-asserted-by":"publisher","award":["322093-03"],"award-info":[{"award-number":["322093-03"]}],"id":[{"id":"10.13039\/501100014189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014189","name":"Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET)","doi-asserted-by":"publisher","award":["2022M3A9E4084134"],"award-info":[{"award-number":["2022M3A9E4084134"]}],"id":[{"id":"10.13039\/501100014189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"Bio &amp; Medical Technology Development Program of the National Research Foundation (NRF)","doi-asserted-by":"publisher","award":["322093-03"],"award-info":[{"award-number":["322093-03"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"Bio &amp; Medical Technology Development Program of the National Research Foundation (NRF)","doi-asserted-by":"publisher","award":["2022M3A9E4084134"],"award-info":[{"award-number":["2022M3A9E4084134"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Wild soybean (Glycine soja, GS) is a traditional medicine used to treat inflammation. In this study, the anti-atopic properties of GS leaf and stem extract on skin inflammation were evaluated in the Dermatophagoides farinae-extract-induced mouse model and keratinocytes. Oral administration of the GS extract reduced scratching, dermatitis score, transepidermal water loss, thickness of epidermis, inflammatory cell accumulation, and serum concentrations of thymic stromal lymphopoietin and immunoglobulin E. GS downregulated the expression of inflammatory gene markers of atopic dermatitis (AD), including interleukin (IL)-6; regulated on activation, normal T cell expressed and secreted (RANTES); thymus- and activation-regulated chemokine (TARC); and macrophage-derived chemokine (MDC) and upregulated the expression of filaggrin, a keratinocyte differentiation marker, in skin tissue. GS downregulated Janus kinase 1, signal transducer and activation of transcription (STAT) 1, and STAT3 pathways. Using ultra-performance liquid chromatography, we identified seven flavonoids in GS extract, including apigenin, epicatechin, genistein, genistin, daidzin, daidzein, and soyasaponin Bb. GS, apigenin, and genistein reduced the expression of IL-6, MDC, TARC, and RANTES and increased filaggrin via the downregulation of STAT3 phosphorylation in interferon-\u03b3\/tumor necrosis factor-\u03b1-stimulated keratinocytes. Our results suggest that GS leaf and stem extract ameliorates AD-like skin inflammation by regulating the immune response and restoring skin barrier function.<\/jats:p>","DOI":"10.3390\/ijms26104560","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T11:25:53Z","timestamp":1746789953000},"page":"4560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Glycine soja Leaf and Stem Extract Ameliorates Atopic Dermatitis-like Skin Inflammation by Inhibiting JAK\/STAT Signaling"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5712-2215","authenticated-orcid":false,"given":"Yoon-Young","family":"Sung","sequence":"first","affiliation":[{"name":"KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misun","family":"Kim","sequence":"additional","affiliation":[{"name":"KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1711-0906","authenticated-orcid":false,"given":"Dong-Seon","family":"Kim","sequence":"additional","affiliation":[{"name":"KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunjung","family":"Son","sequence":"additional","affiliation":[{"name":"KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Afshari, M., Kolackova, M., Rosecka, M., \u010celakovsk\u00e1, J., and Krejsek, J. (2024). Unraveling the skin; a comprehensive review of atopic dermatitis, current understanding, and approaches. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1361005"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jaip.2012.11.005","article-title":"Evaluation of food allergy in patients with atopic dermatitis","volume":"1","author":"Bergmann","year":"2013","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_3","first-page":"30","article-title":"Diet and dermatitis: Food triggers","volume":"7","author":"Katta","year":"2014","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2500\/aap.2019.40.4202","article-title":"Pathophysiology of atopic dermatitis: Clinical implications","volume":"40","author":"Kim","year":"2019","journal-title":"Allergy Asthma Proc."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lee, H., Lee, D.H., Oh, J.H., and Chung, J.H. (2021). Skullcapflavone II suppresses TNF-\u03b1\/IFN-\u03b3-induced TARC, MDC, and CTSS production in HaCaT Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126428"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Huang, I.H., Chung, W.H., Wu, P.C., and Chen, C.B. (2022). JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1068260"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7435621","DOI":"10.1155\/2017\/7435621","article-title":"HaCaT cells as a reliable in vitro differentiation model to dissect the inflammatory\/repair response of human keratinocytes","volume":"2017","author":"Colombo","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"84","DOI":"10.5114\/pdia.2014.40920","article-title":"Chemokines and cytokines network in the pathogenesis of the inflammatory skin diseases: Atopic dermatitis, psoriasis and skin mastocytosis","volume":"31","author":"Nedoszytko","year":"2014","journal-title":"Adv. Dermatol. Allergol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kofsky, J., Zhang, H., and Song, B.H. (2018). The untapped genetic reservoir: The past, current, and future applications of the wild soybean (Glycine soja). Front. Plant Sci., 9.","DOI":"10.3389\/fpls.2018.00949"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ferreira, M.S., Magalh\u00e3es, M.C., Oliveira, R., Sousa-Lobo, J.M., and Almeida, I.F. (2021). Trends in the use of botanicals in anti-aging cosmetics. Molecules, 26.","DOI":"10.3390\/molecules26123584"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7367","DOI":"10.1021\/acs.jafc.8b02016","article-title":"Consumption of Black legumes Glycine soja and Glycine max lowers serum lipids and alters the gut microbiome profile in mice fed a high-fat diet","volume":"66","author":"Jing","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5826","DOI":"10.19082\/5826","article-title":"A review of effective herbal medicines in controlling menopausal symptoms","volume":"9","author":"Kargozar","year":"2017","journal-title":"Electron. Physician"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1468-2494.2010.00522.x","article-title":"Clinical efficacy comparison of anti-wrinkle cosmetics containing herbal flavonoids","volume":"32","author":"Chuarienthong","year":"2010","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lee, Y.M., Son, E., Kim, S.H., and Kim, D.S. (2023). Protective effects of Glycine soja leaf and stem extract against chondrocyte inflammation and osteoarthritis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054829"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.intimp.2008.12.013","article-title":"Dermatophagoides farinae extract induces severe atopic dermatitis in NC\/Nga mice, which is effectively suppressed by the administration of tacrolimus ointment","volume":"9","author":"Oshio","year":"2009","journal-title":"Int. Immunopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kim, M., Yuk, H.J., Min, Y., Kim, D.S., and Sung, Y.Y. (2023). Securinega suffruticosa extract alleviates atopy-like lesions in NC\/Nga mice via inhibition of the JAK1-STAT1\/3 pathway. Biomed. Pharmacother., 169.","DOI":"10.1016\/j.biopha.2023.115903"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s12016-011-8252-4","article-title":"IgE, mast cells, and eosinophils in atopic dermatitis","volume":"41","author":"Liu","year":"2011","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100131","DOI":"10.1016\/j.xjidi.2022.100131","article-title":"Type 2 inflammation contributes to skin barrier dysfunction in atopic dermatitis","volume":"2","author":"Beck","year":"2022","journal-title":"JID Innov."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/s41423-023-00992-4","article-title":"The translational revolution in atopic dermatitis: The paradigm shift from pathogenesis to treatment","volume":"20","author":"Facheris","year":"2023","journal-title":"Cell. Mol. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1242\/jcs.033969","article-title":"Filaggrin in the frontline: Role in skin barrier function and disease","volume":"122","author":"Sandilands","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1046\/j.1365-2249.2002.01727.x","article-title":"Serum macrophage-derived chemokine (MDC) levels are closely related with the disease activity of atopic dermatitis","volume":"127","author":"Kakinuma","year":"2002","journal-title":"Clin. Exp. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yamamura, Y., Nakashima, C., and Otsuka, A. (2024). Interplay of cytokines in the pathophysiology of atopic dermatitis: Insights from murine models and human. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1342176"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6955","DOI":"10.2147\/JIR.S467327","article-title":"Preclinical Models of Atopic Dermatitis Suitable for Mechanistic and Therapeutic Investigations","volume":"17","author":"Maskey","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hatano, Y., and Elias, P.M. (2023). \u201cOutside-to-inside\u201d, \u201cinside-to-outside\u201d, and \u201cintrinsic\u201d endogenous pathogenic mechanisms in atopic dermatitis: Keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1239251"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"106210","DOI":"10.1016\/j.intimp.2020.106210","article-title":"The role of JAK\/STAT signaling pathway and its inhibitors in diseases","volume":"80","author":"Xin","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1016\/j.jaci.2023.07.010","article-title":"The role of Janus kinase signaling in the pathology of atopic dermatitis","volume":"152","author":"Irvine","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coi.2016.05.002","article-title":"Atopic dermatitis and filaggrin","volume":"42","author":"Cabanillas","year":"2016","journal-title":"Curr. Opin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Shim, K.S., Song, H.K., Park, M., Kim, H.J., Jang, S., Kim, T., and Kim, K.M. (2024). Reynoutria japonica consisted of emodin-8-\u03b2-D-glucoside ameliorates Dermatophagoides farinae extract-induced atopic dermatitis-like skin inflammation in mice by inhibiting JAK\/STAT signaling. Biomed. Pharmacother., 176.","DOI":"10.1016\/j.biopha.2024.116765"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Jin, S.E., Seo, C.S., Jeon, W.Y., Oh, Y.J., Shin, H.K., Jeong, H.G., and Ha, H. (2024). Evodiae Fructus extract suppresses inflammatory response in HaCaT cells and improves house dust mite-induced atopic dermatitis in NC\/Nga mice. Sci. Rep., 14.","DOI":"10.1038\/s41598-023-50257-3"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kim, H.J., Park, M., Jang, S., Song, H.K., Lee, S.K., and Kim, T. (2025). Pulsatilla koreana Nakai Extract Attenuates Atopic Dermatitis-like Symptoms by Regulating Skin Barrier Factors and Inhibiting the JAK\/STAT Pathway. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26072994"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"139883","DOI":"10.1016\/j.foodchem.2024.139883","article-title":"Localization in soybean seeds: Comparative analysis of wild (Glycine soja) and cultivated (Glycine max) varieties","volume":"456","author":"Ren","year":"2024","journal-title":"Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.intimp.2019.01.054","article-title":"Genistein suppresses psoriasis-related inflammation through a STAT3-NF-\u03baB-dependent mechanism in keratinocytes","volume":"69","author":"Wang","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"293","DOI":"10.3177\/jnsv.52.293","article-title":"Genistein suppresses development of spontaneous atopic-like dermatitis in NC\/Nga mice","volume":"52","author":"Sakai","year":"2006","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Park, C.H., Min, S.Y., Yu, H.W., Kim, K., Kim, S., Lee, H.J., Kim, J.H., and Park, Y.J. (2020). Effects of apigenin on RBL-2H3, RAW264.7, and HaCaT cells: Anti-allergic, anti-inflammatory, and skin-protective activities. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134620"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"121909","DOI":"10.1016\/j.lfs.2023.121909","article-title":"Anti-inflammatory, anti-proliferative and anti-psoriatic potential of apigenin in RAW 264.7 cells, HaCaT cells and psoriasis like dermatitis in BALB\/c mice","volume":"328","author":"Singh","year":"2023","journal-title":"Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"912028","DOI":"10.1155\/2012\/912028","article-title":"Topical apigenin alleviates cutaneous inflammation in murine models","volume":"2012","author":"Man","year":"2012","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Che, D.N., Cho, B.O., Shin, J.Y., Kang, H.J., Kim, J.S., Oh, H., Kim, Y.S., and Jang, S.I. (2019). Apigenin inhibits IL-31 cytokine in human mast cell and mouse skin tissues. Molecules, 24.","DOI":"10.3390\/molecules24071290"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.ejmech.2016.08.066","article-title":"Inhibition of the enzymes in the leukotriene and prostaglandin pathways in inflammation by 3-aryl isocoumarins","volume":"124","author":"Ramanan","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Alessandrello, C., Sanfilippo, S., Minciullo, P.L., and Gangemi, S. (2024). An overview on atopic dermatitis, oxidative stress, and psychological stress: Possible role of nutraceuticals as an additional therapeutic strategy. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25095020"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/bjd\/ljae342","article-title":"A practical guide to using oral Janus kinase inhibitors for atopic dermatitis from the International Eczema Council","volume":"192","author":"Haag","year":"2024","journal-title":"Br. J. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jaci.2021.08.009","article-title":"JAK inhibitors in the treatment of atopic dermatitis","volume":"148","author":"Chovatiya","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"114021","DOI":"10.1016\/j.jep.2021.114021","article-title":"Efficacy and action mechanisms of a Chinese herbal formula on experimental models of atopic dermatitis","volume":"274","author":"Wang","year":"2021","journal-title":"J. Ethnopharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4560\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:30:19Z","timestamp":1760031019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4560"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,9]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26104560"],"URL":"https:\/\/doi.org\/10.3390\/ijms26104560","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,9]]}}}