{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T16:09:00Z","timestamp":1789229340185,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Priority Research Center Program Grant","award":["NRF-2021R1A6A1A03038865"],"award-info":[{"award-number":["NRF-2021R1A6A1A03038865"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atopic dermatitis (AD) is a common allergic inflammatory skin condition marked by severe itching, skin lichenification, and chronic inflammation. AD results from a complex immune response, primarily driven by T lymphocytes and environmental triggers, leading to a disrupted epidermal barrier function. Traditional treatments, such as topical corticosteroids, have limitations due to long-term side effects, highlighting the need for safer alternatives. Here, we aimed to show that Agrimonia coreana extract (ACext) can be used in treating AD-related dermatologic symptoms. ACext could inhibit CRAC (Calcium Release-Activated Calcium) channel activity, reducing Orai1\/CRAC currents and decreasing intracellular calcium signaling. This inhibition was further confirmed by the reduced IL-2 levels and T cell proliferation upon ACext treatment. In a mouse model of AD, ACext significantly ameliorates symptoms, improves histological parameters, and enhances skin barrier function, demonstrating its potential for treating AD.<\/jats:p>","DOI":"10.3390\/ijms25168894","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T09:29:41Z","timestamp":1723714181000},"page":"8894","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Agrimonia coreana Extract Exerts Its Therapeutic Effect through CRAC Channel Inhibition for Atopic Dermatitis Treatment"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9817-6726","authenticated-orcid":false,"given":"Jintae","family":"Kim","sequence":"first","affiliation":[{"name":"Channelopathy Research Center (CRC), Dongguk University College of Medicine, 32 Dongguk-ro, Ilsan Dong-gu, Goyang 10326, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Channelopathy Research Center (CRC), Dongguk University College of Medicine, 32 Dongguk-ro, Ilsan Dong-gu, Goyang 10326, Gyeonggi-do, Republic of Korea"},{"name":"Department of Physiology, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Jin","family":"Park","sequence":"additional","affiliation":[{"name":"Channelopathy Research Center (CRC), Dongguk University College of Medicine, 32 Dongguk-ro, Ilsan Dong-gu, Goyang 10326, Gyeonggi-do, Republic of Korea"},{"name":"Department of Physiology, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7816-2585","authenticated-orcid":false,"given":"Yu Ran","family":"Nam","sequence":"additional","affiliation":[{"name":"CiPA Korea Inc., Ilsan Seo-gu, Goyang 10911, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7906-495X","authenticated-orcid":false,"given":"Seong Woo","family":"Choi","sequence":"additional","affiliation":[{"name":"Channelopathy Research Center (CRC), Dongguk University College of Medicine, 32 Dongguk-ro, Ilsan Dong-gu, Goyang 10326, Gyeonggi-do, Republic of Korea"},{"name":"Department of Physiology, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Hyun","family":"Nam","sequence":"additional","affiliation":[{"name":"Channelopathy Research Center (CRC), Dongguk University College of Medicine, 32 Dongguk-ro, Ilsan Dong-gu, Goyang 10326, Gyeonggi-do, Republic of Korea"},{"name":"Department of Physiology, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6130-7028","authenticated-orcid":false,"given":"Hyun Jong","family":"Kim","sequence":"additional","affiliation":[{"name":"Channelopathy Research Center (CRC), Dongguk University College of Medicine, 32 Dongguk-ro, Ilsan Dong-gu, Goyang 10326, Gyeonggi-do, Republic of Korea"},{"name":"Department of Physiology, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0359-3967","authenticated-orcid":false,"given":"Woo Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Gyeongsangbuk-do, Republic of Korea"},{"name":"Department of Internal Medicine, Graduate School of Medicine, Dongguk University, 27 Dongguk-ro, Ilsan Dong-gu, Goyang 10326, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sroka-Tomaszewska, J., and Trzeciak, M. (2021). Molecular Mechanisms of Atopic Dermatitis Pathogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084130"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1056\/NEJMra074081","article-title":"Atopic dermatitis","volume":"358","author":"Bieber","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3742208","DOI":"10.1155\/2022\/3742208","article-title":"Agrimonia pilosa: A Phytochemical and Pharmacological Review","volume":"2022","author":"Jin","year":"2022","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e09972","DOI":"10.1016\/j.heliyon.2022.e09972","article-title":"Agrimonia pilosa Ledeb.: A review of its traditional uses, botany, phytochemistry, pharmacology, and toxicology","volume":"8","author":"Wen","year":"2022","journal-title":"Heliyon"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Park, S.J., Lee, J.S., Nam, Y.R., Lee, J.M., Ki, D.W., Yun, B.S., Choi, S.W., Van, N.T.H., Nam, J.H., and Kim, H.J. (2023). Anti-Inflammatory Effects of Alphitolic Acid Isolated from Agrimonia coreana Nakai Extracts Are Mediated via the Inhibition of I(CRAC) Activity in T Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417309"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3109\/08820130903501790","article-title":"Inhibitory effect of Agrimonia pilosa Ledeb. on inflammation by suppression of iNOS and ROS production","volume":"39","author":"Jung","year":"2010","journal-title":"Immunol. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jep.2011.12.035","article-title":"Anti-inflammatory and anti-allergic effects of Agrimonia pilosa Ledeb extract on murine cell lines and OVA-induced airway inflammation","volume":"140","author":"Kim","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.jdermsci.2017.03.003","article-title":"Agrimonia pilosa leaf extract accelerates skin barrier restoration by activation of transient receptor potential vanilloid 3","volume":"86","author":"Nam","year":"2017","journal-title":"J. Dermatol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-immunol-032414-112212","article-title":"Ion channels in innate and adaptive immunity","volume":"33","author":"Feske","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ceca.2019.01.003","article-title":"CRAC channel regulation of innate immune cells in health and disease","volume":"78","author":"Clemens","year":"2019","journal-title":"Cell Calcium"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrd3136","article-title":"Store-operated CRAC channels: Function in health and disease","volume":"9","author":"Parekh","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3389\/fimmu.2020.00195","article-title":"The Role of Calcium-Calcineurin-NFAT Signaling Pathway in Health and Autoimmune Diseases","volume":"11","author":"Park","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.it.2020.06.012","article-title":"CRAC Channels and Calcium Signaling in T Cell-Mediated Immunity","volume":"41","author":"Vaeth","year":"2020","journal-title":"Trends Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1096\/fba.2020-00008","article-title":"Anti-ORAI1 antibody DS-2741a, a specific CRAC channel blocker, shows ideal therapeutic profiles for allergic disease via suppression of aberrant T-cell and mast cell activation","volume":"2","author":"Aki","year":"2020","journal-title":"FASEB BioAdvances"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ceca.2018.07.005","article-title":"CRAC channels as targets for drug discovery and development","volume":"74","author":"Stauderman","year":"2018","journal-title":"Cell Calcium"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1093\/hmg\/ddz223","article-title":"Single-nucleotide polymorphisms in Orai1 associated with atopic dermatitis inhibit protein turnover, decrease calcium entry and disrupt calcium-dependent gene expression","volume":"29","author":"Yeh","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2013.08.057","article-title":"The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch","volume":"155","author":"Wilson","year":"2013","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev-immunol-042617-053352","article-title":"Signaling and Function of Interleukin-2 in T Lymphocytes","volume":"36","author":"Ross","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/sj.jid.5701011","article-title":"Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: Structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges","volume":"128","author":"Man","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1159\/000247298","article-title":"Severity scoring of atopic dermatitis: The SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis","volume":"186","author":"Schallreuter","year":"1993","journal-title":"Dermatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s10753-023-01943-x","article-title":"Characterization of Different Inflammatory Skin Conditions in a Mouse Model of DNCB-Induced Atopic Dermatitis","volume":"47","author":"Riedl","year":"2024","journal-title":"Inflammation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1016\/j.jid.2018.09.001","article-title":"Research Techniques Made Simple: Transepidermal Water Loss Measurement as a Research Tool","volume":"138","author":"Alexander","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_23","first-page":"95","article-title":"The Role of Impaired Epidermal Barrier Function in Atopic Dermatitis","volume":"24","author":"Marinovic","year":"2016","journal-title":"Acta Dermatovenerol. Croat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/s41385-022-00505-y","article-title":"Skin immunity: Dissecting the complex biology of our body\u2019s outer barrier","volume":"15","author":"Zhang","year":"2022","journal-title":"Mucosal Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s11882-014-0433-9","article-title":"Skin barrier defects in atopic dermatitis","volume":"14","author":"Agrawal","year":"2014","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s10565-020-09536-2","article-title":"TRPV3 enhances skin keratinocyte proliferation through EGFR-dependent signaling pathways","volume":"37","author":"Wang","year":"2021","journal-title":"Cell Biol. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Um, J.Y., Kim, H.B., Kim, J.C., Park, J.S., Lee, S.Y., Chung, B.Y., Park, C.W., and Kim, H.O. (2022). TRPV3 and Itch: The Role of TRPV3 in Chronic Pruritus according to Clinical and Experimental Evidence. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314962"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105040","DOI":"10.1016\/j.phrs.2020.105040","article-title":"Targeting T cells in inflammatory bowel disease","volume":"159","author":"Giuffrida","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2174\/1389450120666190926150258","article-title":"Structural and Mechanistic Insights of CRAC Channel as a Drug Target in Autoimmune Disorder","volume":"21","author":"Bhuvaneshwari","year":"2020","journal-title":"Curr. Drug Targets"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Guo, Y., Song, Y., Liu, W., Wang, T., Ma, X., and Yu, Z. (2023). Novel Insights into the Role of Keratinocytes-Expressed TRPV3 in the Skin. Biomolecules, 13.","DOI":"10.3390\/biom13030513"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jid.2017.07.852","article-title":"Activation of TRPV3 Regulates Inflammatory Actions of Human Epidermal Keratinocytes","volume":"138","author":"Szollosi","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e104","DOI":"10.1002\/ski2.104","article-title":"Transepidermal water loss (TEWL): Environment and pollution-A systematic review","volume":"2","author":"Green","year":"2022","journal-title":"Skin. Health Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jdin.2023.05.012","article-title":"Risk of skin atrophy induced by short-term topical corticosteroid use in atopic dermatitis lesional skin: A systematic review","volume":"12","author":"Ricardo","year":"2023","journal-title":"JAAD Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1046\/j.1365-2133.2003.05356.x","article-title":"Topical corticosteroid treatment: Systemic side-effects","volume":"149","author":"Kane","year":"2003","journal-title":"Br. J. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1067\/mai.2000.106927","article-title":"Clinical cross-reactivity among foods of the Rosaceae family","volume":"106","author":"Rodriguez","year":"2000","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7423","DOI":"10.1080\/10408398.2022.2045897","article-title":"Rosaceae food allergy: A review","volume":"63","author":"Costa","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.cell.2010.03.013","article-title":"TRP channel regulates EGFR signaling in hair morphogenesis and skin barrier formation","volume":"141","author":"Cheng","year":"2010","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.jaip.2023.03.022","article-title":"A Comparison of Topical Corticosteroids and Topical Calcineurin Inhibitors for the Treatment of Atopic Dermatitis","volume":"11","author":"Pena","year":"2023","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"363","DOI":"10.4196\/kjpp.2020.24.4.363","article-title":"Gardenia jasminoides extract and its constituent, genipin, inhibit activation of CD3\/CD28 co-stimulated CD4(+) T cells via ORAI1 channel","volume":"24","author":"Kim","year":"2020","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"251","DOI":"10.4196\/kjpp.2021.25.3.251","article-title":"Flos magnoliae constituent fargesin has an anti-allergic effect via ORAI1 channel inhibition","volume":"25","author":"Hong","year":"2021","journal-title":"Korean J. Physiol. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8894\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:37:09Z","timestamp":1760110629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8894"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,15]]},"references-count":40,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25168894"],"URL":"https:\/\/doi.org\/10.3390\/ijms25168894","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,15]]}}}