{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T05:18:36Z","timestamp":1793683116489,"version":"4.5.1"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Commercializations Promotion Agency for R&amp;D Outcomes (COMPA)","award":["2021-DD-RD-0421-01-101"],"award-info":[{"award-number":["2021-DD-RD-0421-01-101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As one of the major intractable allergic disorders, atopic inflammation is commonly accompanied by itching, dry skin, and inflammation. Atopic inflammation deteriorates the quality of life and has no fundamental cure, so it is crucial to urgently explore and develop natural resources for long-term treatment without any side effects. This study aimed to verify Torilis japonica extract (TJE)\u2019s relieving effect and mechanism against atopic inflammation using skin cells and skin equivalent models, as well as to investigate torilin\u2019s effect (obtained from TJE) and other unknown components as marker compounds. Torilin concentration was verified in TJE using high-performance liquid chromatography and analyzed the unknown components using nuclear magnetic resonance spectroscopy. Furthermore, TJE\u2019s cytotoxicity, regenerative effect, and cell cycle regulation effects were confirmed using skin cells with atopic inflammation (human dermal fibroblasts and HaCaT keratinocytes) by using TNF-\u03b1 and IFN-\u03b3 treatments. Consequently, TJE was demonstrated to regulate TARC and CTACK expressions as chemokines and those of interleukin-4, -5, and -13 as cytokines related to atopic inflammation. TJE was further confirmed to affect the matrix metalloproteinase-1, -2, and -9 expressions, which are essential in skin damage. Lastly, this study confirmed TJE\u2019s relieving effect against atopic inflammation through a 3D skin model and RhCE model using human dermal fibroblasts and HaCaT keratinocytes. These findings on atopic inflammation verified torilin\u2019s relieving effects and TJE\u2019s other components.<\/jats:p>","DOI":"10.3390\/ijms24032102","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T06:52:41Z","timestamp":1674197561000},"page":"2102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Torilis japonica Extract Suppresses the Induction of Atopic Inflammation"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2914-3526","authenticated-orcid":false,"given":"Ji-Won","family":"Seo","sequence":"first","affiliation":[{"name":"Department of Biological Science and Biotechnology, College of Life Science and Nano Technology, Hannam University, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8261-9031","authenticated-orcid":false,"given":"Hyo-Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Biotechnology, College of Life Science and Nano Technology, Hannam University, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Mi","family":"Youk","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Biotechnology, College of Life Science and Nano Technology, Hannam University, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7737-8947","authenticated-orcid":false,"given":"Gun-He","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Biotechnology, College of Life Science and Nano Technology, Hannam University, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Biotechnology, College of Life Science and Nano Technology, Hannam University, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nam, G.H., Jo, K.J., Park, Y.S., Kawk, H.W., Yoo, J.G., Jang, J.D., Kang, S.M., Kim, S.Y., and Kim, Y.M. (2019). Bacillus\/Trapa japonica Fruit Extract Ferment Filtrate enhances human hair follicle dermal papilla cell proliferation via the Akt\/ERK\/GSK-3\u03b2 signaling pathway. BMC Complement. Altern. Med., 19.","DOI":"10.1186\/s12906-019-2514-8"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000370220","article-title":"Atopic dermatitis: Global epidemiology and risk factors","volume":"66","author":"Nutten","year":"2015","journal-title":"Ann. Nutr. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.jaci.2016.06.010","article-title":"Cellular and molecular immunologic mechanisms in patients with atopic dermatitis","volume":"138","author":"Werfel","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"eaah4680","DOI":"10.1126\/scitranslmed.aah4680","article-title":"Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis","volume":"9","author":"Nakatsuji","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.fct.2017.10.025","article-title":"Chrysin attenuates atopic dermatitis by suppressing inflammation of keratinocytes","volume":"110","author":"Choi","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","unstructured":"Gallegos-Alcal\u00e1, P., Jim\u00e9nez, M., Cervantes-Garc\u00eda, D., and Salinas, E. (2021). The Keratinocyte as a Crucial Cell in the Predisposition, Onset, Progression, Therapy and Study of the Atopic Dermatitis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910661"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.alit.2016.12.002","article-title":"Atopic dermatitis: Immune deviation, barrier dysfunction, IgE autoreactivity and new therapies","volume":"66","author":"Furue","year":"2017","journal-title":"Allergol. Int."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mittermann, I., Wikberg, G., Johansson, C., Lupinek, C., Lundeberg, L., Crameri, R., Valenta, R., and Scheynius, A. (2016). IgE sensitization profiles differ between adult patients with severe and moderate atopic dermatitis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156077"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1016\/j.jid.2016.05.127","article-title":"Staphylococcus aureus exploits epidermal barrier defects in atopic dermatitis to trigger cytokine expression","volume":"136","author":"Nakatsuji","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1111\/jdv.12753","article-title":"Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1\/Th2\/Th17 cytokines in adults with atopic dermatitis","volume":"29","author":"Batista","year":"2015","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.jaci.2016.08.023","article-title":"Multiplex platform technology and bioinformatics are essential for development of biomarkers in atopic dermatitis","volume":"139","author":"Thijs","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1097\/ACI.0000000000000198","article-title":"Biomarkers for atopic dermatitis: A systematic review and meta-analysis","volume":"15","author":"Thijs","year":"2015","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1089\/ped.2016.0703","article-title":"Biomarkers for Atopic Dermatitis in Children","volume":"29","year":"2016","journal-title":"Pediatr. Allergy Immunol. Pulmonol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1111\/jphp.12640","article-title":"Effects of Hovenia dulcis Thunb. extract and methyl vanillate on atopic dermatitis-like skin lesions and TNF-\u03b1\/IFN-\u03b3-induced chemokines production in HaCaT cells","volume":"68","author":"Lim","year":"2016","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1080\/1744666X.2017.1298443","article-title":"Commonality of the IL-4\/IL-13 pathway in atopic diseases","volume":"13","author":"Gandhi","year":"2017","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1016\/j.jaci.2017.12.1002","article-title":"New mechanism underlying IL-31\u2013induced atopic dermatitis","volume":"141","author":"Meng","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/cdd.2015.162","article-title":"\u0394Np63 regulates IL-33 and IL-31 signaling in atopic dermatitis","volume":"23","author":"Rizzo","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Piipponen, M., Li, D., and Land\u00e9n, N.X. (2020). The immune functions of keratinocytes in skin wound healing. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228790"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2147\/ITT.S260370","article-title":"Targeting IL-4 for the treatment of atopic dermatitis","volume":"9","author":"Chiricozzi","year":"2020","journal-title":"Immunotargets Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.rmed.2015.04.004","article-title":"IL-5, IL-8 and MMP-9 levels in exhaled breath condensate of atopic and nonatopic asthmatic children","volume":"109","author":"Turkeli","year":"2015","journal-title":"Respir. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8707","DOI":"10.1038\/s41598-017-09207-z","article-title":"The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins","volume":"7","author":"Brunner","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s11030-017-9804-1","article-title":"An integrated structure-and pharmacophore-based MMP-12 virtual screening","volume":"22","author":"Ramezani","year":"2018","journal-title":"Mol. Divers."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.dental.2016.03.008","article-title":"Collagen cross-linkers on dentin bonding: Stability of the adhesive interfaces, degree of conversion of the adhesive, cytotoxicity and in situ MMP inhibition","volume":"32","author":"Hass","year":"2016","journal-title":"Dent. Mater."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Van Hove, I., Lefevere, E., De Groef, L., Sergeys, J., Salinas-Navarro, M., Libert, C., Vandenbroucke, R., and Moons, L. (2016). MMP-3 deficiency alleviates endotoxin-induced acute inflammation in the posterior eye segment. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111825"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"406","DOI":"10.3389\/fonc.2019.00406","article-title":"In vitro and in vivo Induction of p53-Dependent Apoptosis by Extract of Euryale ferox Salisb in A549 Human Caucasian Lung Carcinoma Cancer Cells Is Mediated Through Akt Signaling Pathway","volume":"9","author":"Nam","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.3892\/ijo.2016.3578","article-title":"Torilis japonica extract-generated intracellular ROS induces apoptosis by reducing the mitochondrial membrane potential via regulation of the AMPK-p38 MAPK signaling pathway in HCT116 colon cancer","volume":"49","author":"Kim","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5895029","DOI":"10.1155\/2020\/5895029","article-title":"Antiaging Activity of Peptide Identified from Fermented Trapa japonica Fruit Extract in Human Dermal Fibroblasts","volume":"2020","author":"Jang","year":"2020","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s11418-017-1123-4","article-title":"Sesquiterpenes from fruits of Torilis japonica with inhibitory activity on melanin synthesis in B16 cells","volume":"72","author":"Jo","year":"2018","journal-title":"J. Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S58","DOI":"10.1016\/j.jaci.2017.01.008","article-title":"Clinical phenotypes and endophenotypes of atopic dermatitis: Where are we, and where should we go?","volume":"139","author":"Bieber","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Venkatesan, J., Anil, S., Kim, S.K., and Shim, M. (2017). Marine fish proteins and peptides for cosmeceuticals: A review. Mar. Drugs, 15.","DOI":"10.3390\/md15050143"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ijpharm.2015.01.030","article-title":"Cell penetrating peptide conjugated liposomes as transdermal delivery system of Polygonum aviculare L. extract","volume":"483","author":"Kwon","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jep.2016.03.028","article-title":"Anti-inflammatory and anti-allergic effects and underlying mechanisms of Huang-Lian-Jie-Du extract: Implication for atopic dermatitis treatment","volume":"185","author":"Chen","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tsang, M.S.M., Jiao, D., Chan, B.C.L., Hon, K.L., Leung, P.C., Lau, C.B.S., Wong, E.C.W., Cheng, L., Chan, C.K.M., and Lam, C.W.K. (2016). Anti-inflammatory activities of pentaherbs formula, berberine, gallic acid and chlorogenic acid in atopic dermatitis-like skin inflammation. Molecules, 21.","DOI":"10.3390\/molecules21040519"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2102\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:12:12Z","timestamp":1760119932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,20]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032102"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032102","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,20]]}}}