{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:03:56Z","timestamp":1766048636239,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2015,12,25]],"date-time":"2015-12-25T00:00:00Z","timestamp":1451001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>We evaluated the anti-atopic dermatitis (AD) effect of Atofreellage (AF), a herbal formula composed of 10 medicinal plants. AD was induced on the dorsal skin areas of NC\/Nga mice (male, seven weeks old) by daily application of 2,4-dinitrochlorobenzene (DNCB) for five weeks. After three weeks of DNCB application, 200 \u03bcL of AF (0, 25, 50 or 100 mg\/mL) was applied to the skin lesions. Histological findings, blood cell populations, serum levels of immunoglobulin E (IgE), histamine, pro-inflammatory cytokines, and inflammatory signaling in the skin tissue, and T-helper cell type 2 (Th2)-related cytokines in splenocytes were analyzed. Histopathological findings showed AF treatment notably attenuated the thickness of dorsal skin, and eosinophil infiltration. AF treatment (especially 100 mg\/mL) also demonstrably ameliorated the blood cell population abnormalities, as the notable elevation of serum concentrations of IgE, histamine, TNF-\u03b1, IL-6 and IL-1\u03b2 were remarkably normalized by AF treatment. Western blot analysis evidenced the apparent normalization of inflammatory signals (ERK, p38 MAP kinase, JNK, and NF-\u03baB) in the skin tissue. Additionally, AF treatment notably attenuated the activation of Th2-dominant cytokines (IL-13, IL-4, and IL-5) in Con A-treated splenocytes in an ex vivo assay. In conclusion, this study provides experimental evidence for the clinical relevance of Atofreellage.<\/jats:p>","DOI":"10.3390\/molecules21010035","type":"journal-article","created":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T04:23:49Z","timestamp":1451276629000},"page":"35","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Herbal Formula, Atofreellage, Ameliorates Atopic Dermatitis-Like Skin Lesions in an NC\/Nga Mouse Model"],"prefix":"10.3390","volume":"21","author":[{"given":"Won-Yong","family":"Kim","sequence":"first","affiliation":[{"name":"Liver and Immunology Research-Center, Daejeon Oriental Hospital of Daejeon University, 176-9, Daeheung-ro, Jung-Gu, Daejeon 34929, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeong-Geug","family":"Kim","sequence":"additional","affiliation":[{"name":"Liver and Immunology Research-Center, Daejeon Oriental Hospital of Daejeon University, 176-9, Daeheung-ro, Jung-Gu, Daejeon 34929, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye-Won","family":"Lee","sequence":"additional","affiliation":[{"name":"TKM-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Daejeon 34054, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Liver and Immunology Research-Center, Daejeon Oriental Hospital of Daejeon University, 176-9, Daeheung-ro, Jung-Gu, Daejeon 34929, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hwi-Jin","family":"Im","sequence":"additional","affiliation":[{"name":"Liver and Immunology Research-Center, Daejeon Oriental Hospital of Daejeon University, 176-9, Daeheung-ro, Jung-Gu, Daejeon 34929, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyo-Seon","family":"Kim","sequence":"additional","affiliation":[{"name":"Liver and Immunology Research-Center, Daejeon Oriental Hospital of Daejeon University, 176-9, Daeheung-ro, Jung-Gu, Daejeon 34929, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Bae","family":"Lee","sequence":"additional","affiliation":[{"name":"Liver and Immunology Research-Center, Daejeon Oriental Hospital of Daejeon University, 176-9, Daeheung-ro, Jung-Gu, Daejeon 34929, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Gue","family":"Son","sequence":"additional","affiliation":[{"name":"Liver and Immunology Research-Center, Daejeon Oriental Hospital of Daejeon University, 176-9, Daeheung-ro, Jung-Gu, Daejeon 34929, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2500\/aap.2012.33.3569","article-title":"Epidemiology of atopic dermatitis: A review","volume":"33","author":"DaVeiga","year":"2012","journal-title":"Allergy Asthma Proc."},{"key":"ref_2","first-page":"35","article-title":"Atopic dermatitis: An overview","volume":"86","author":"Berke","year":"2012","journal-title":"Am. Fam. Phys."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0738-081X(02)00360-7","article-title":"The epidemiology of atopic dermatitis","volume":"21","author":"Levy","year":"2003","journal-title":"Clin. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1007\/s12016-007-0029-4","article-title":"Mast cells and immunological skin diseases","volume":"33","author":"Navi","year":"2007","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0140-6736(03)12193-9","article-title":"Atopic dermatitis","volume":"361","author":"Leung","year":"2003","journal-title":"Lancet"},{"key":"ref_6","unstructured":"Bantz, S.K., Zhu, Z., and Zheng, T. (2014). The atopic March: Progression from atopic dermatitis to allergic rhinitis and asthma. J. Clin. Cell. Immunol., 5."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1097\/00130832-200310000-00001","article-title":"Environmental exposure to endotoxin and other microbial products and the decreased risk of childhood atopy: Evaluating developments since April 2002","volume":"3","year":"2003","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1185\/03007990903512156","article-title":"Atopic dermatitis: A review of topical treatment options","volume":"26","author":"Simpson","year":"2010","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"40","DOI":"10.5021\/ad.2015.27.1.40","article-title":"Disease awareness and management behavior of patients with atopic dermatitis: A questionnaire survey of 313 patients","volume":"27","author":"Kim","year":"2015","journal-title":"Ann. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1529-8019.2007.00137.x","article-title":"Systemic ciclosporin and tacrolimus in dermatology","volume":"20","author":"Madan","year":"2007","journal-title":"Dermatol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.clindermatol.2014.12.005","article-title":"Systemic therapy of childhood atopic dermatitis","volume":"33","author":"Slater","year":"2015","journal-title":"Clin. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1136\/bmj.324.7353.1533","article-title":"New treatments for atopic dermatitis","volume":"324","author":"Williams","year":"2002","journal-title":"BMJ"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jep.2012.08.042","article-title":"Topical application of an ethanol extract prepared from Illicium verum suppresses atopic dermatitis in NC\/Nga mice","volume":"144","author":"Sung","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.jep.2012.10.015","article-title":"Effects of Catalpa ovata stem bark on atopic dermatitis-like skin lesions in NC\/Nga mice","volume":"145","author":"Yang","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S118","DOI":"10.1016\/j.jaci.2003.09.033","article-title":"Atopic dermatitis and the atopic march","volume":"112","author":"Spergel","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1067\/mai.2000.106484","article-title":"Atopic dermatitis: New insights and opportunities for therapeutic intervention","volume":"105","author":"Leung","year":"2000","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/j.1398-9995.2006.01153.x","article-title":"Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology\/American Academy of Allergy, Asthma and Immunology\/PRACTALL Consensus Report","volume":"61","author":"Akdis","year":"2006","journal-title":"Allergy"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jep.2014.11.018","article-title":"Use of traditional Chinese medicine reduces exposure to corticosteroid among atopic dermatitis children: A 1-year follow-up cohort study","volume":"159","author":"Chen","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jdermsci.2004.02.013","article-title":"Animal models for atopic dermatitis: Are they relevant to human disease?","volume":"36","author":"Shiohara","year":"2004","journal-title":"J. Dermatol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.ad.2011.07.013","article-title":"Omalizumab for the treatment of atopic dermatitis","volume":"103","author":"Paravisini","year":"2012","journal-title":"Actas DermoSifiliogr."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhang, E.Y., Chen, A.Y., and Zhu, B.T. (2009). Mechanism of dinitrochlorobenzene-induced dermatitis in mice: Role of specific antibodies in pathogenesis. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007703"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1542\/peds.2011-2382","article-title":"Allergy testing in childhood: Using allergen-specific IgE tests","volume":"129","author":"Sicherer","year":"2012","journal-title":"Pediatrics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bbadis.2010.12.014","article-title":"Mast cells and inflammation","volume":"1822","author":"Theoharides","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1592\/phco.28.12.1495","article-title":"Association of the histamine N-methyltransferase C314T (Thr105Ile) polymorphism with atopic dermatitis in Caucasian children","volume":"28","author":"Kennedy","year":"2008","journal-title":"Pharmacotherapy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1016\/j.jaci.2009.11.017","article-title":"IgE, mast cells, basophils, and eosinophils","volume":"125","author":"Stone","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_26","first-page":"357","article-title":"Desoximetasone 0.25% and tacrolimus 0.1% ointments versus tacrolimus alone in the treatment of atopic dermatitis","volume":"78","author":"Hebert","year":"2006","journal-title":"Cutis"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/S0952-7915(02)00388-6","article-title":"Allergy immunotherapy and inhibition of Th2 immune responses: A sufficient strategy?","volume":"14","author":"Lewis","year":"2002","journal-title":"Curr. Opin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/j.2040-1124.2010.00046.x","article-title":"Relationship between urinary sodium excretion and pioglitazone-induced edema","volume":"1","author":"Nakamura","year":"2010","journal-title":"J. Diabetes Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.jaci.2007.06.015","article-title":"Anti-IgE treatment of eosinophil-associated gastrointestinal disorders","volume":"120","author":"Foroughi","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0167-5699(99)01492-9","article-title":"Atopy and asthma: Genetic variants of IL-4 and IL-13 signalling","volume":"21","author":"Shirakawa","year":"2000","journal-title":"Immunol. Today"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1046\/j.1365-2249.2001.01602.x","article-title":"Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma","volume":"125","author":"Wong","year":"2001","journal-title":"Clin. Exp. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1248\/bpb.25.809","article-title":"Anti-allergic effects of cnidii monnieri fructus (dried fruits of Cnidium monnieri) and its major component, osthol","volume":"25","author":"Matsuda","year":"2002","journal-title":"Biol. Pharm. Bull."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jep.2008.01.013","article-title":"Suppressive effects of Houttuynia cordata Thunb (Saururaceae) extract on Th2 immune response","volume":"117","author":"Lee","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1093\/ecam\/neh077","article-title":"Kampo medicines for mite antigen-induced allergic dermatitis in NC\/Nga mice","volume":"2","author":"Gao","year":"2005","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3831\/KPI.2012.15.2.007","article-title":"Effect of lithospermi radix on contact dermatitis induced by dinitrofluorobenzene in mice","volume":"15","author":"Kim","year":"2012","journal-title":"J. Pharmacopunct."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3892\/ijmm.2014.2006","article-title":"Cinnamomum cassia bark produced by solid-state fermentation with Phellinus baumii has the potential to alleviate atopic dermatitis-related symptoms","volume":"35","author":"Shin","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.1016\/S0002-9343(02)01437-7","article-title":"Complementary and alternative medicine herbal therapies for atopic disorders","volume":"113","author":"Zuckerman","year":"2002","journal-title":"Am. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/toxsci\/kfj063","article-title":"Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells","volume":"91","author":"Kim","year":"2006","journal-title":"Toxicol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.3390\/molecules18032483","article-title":"Anti-inflammatory and anti-allergic activities of Pentaherb formula, Moutan Cortex (Danpi) and gallic acid","volume":"18","author":"Liu","year":"2013","journal-title":"Molecules"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1248\/bpb.29.64","article-title":"Caffeic acid inhibits compound 48\/80-induced allergic symptoms in mice","volume":"29","author":"Hossen","year":"2006","journal-title":"Biol. Pharm. Bull."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ha, H., Lee, H., Seo, C.S., Lim, H.S., Lee, J.K., Lee, M.Y., and Shin, H. (2014). Artemisia capillaris inhibits atopic dermatitis-like skin lesions in Dermatophagoides farinae-sensitized Nc\/Nga mice. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-100"},{"key":"ref_42","unstructured":"World Health Organization (2000). General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine, World Health Organization."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nbt.3167","article-title":"A systems approach to traditional oriental medicine","volume":"33","author":"Kim","year":"2015","journal-title":"Nat. Biotechnol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/1\/35\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:54:52Z","timestamp":1760216092000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/1\/35"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,25]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,1]]}},"alternative-id":["molecules21010035"],"URL":"https:\/\/doi.org\/10.3390\/molecules21010035","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2015,12,25]]}}}