{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:36:20Z","timestamp":1788543380251,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003718","name":"Korean Institute of Oriental Medicine","doi-asserted-by":"publisher","award":["KSN1927331"],"award-info":[{"award-number":["KSN1927331"]}],"id":[{"id":"10.13039\/501100003718","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Current asthma therapies reduce inflammation and symptoms but there are concerns regarding adverse effects and the long-term treatment burden. The anti-asthmatic potential of Dictamnine (Dic) has not been investigated. The therapeutic effect of Dic on airway inflammation and remodeling was investigated by targeting the tumor growth factor (TGF)-\u03b2\/Smad2\/3 pathway. A murine model of ovalbumin (OVA)-induced asthma was used to evaluate the effects of orally-administered Dic on airway hyperresponsiveness, inflammatory cytokines in bronchoalveolar lavage fluid (BALF), OVA-specific IgE in the serum, and histopathological changes. The expression of TGF-\u03b2\/Smad2\/3 and epithelial markers was assessed. Human bronchial epithelial cells were used in vitro to examine the effects of Dic on TGF-\u03b2-induced Smad2\/3 phosphorylation. Network pharmacology was conducted to predict Dic-associated targets and pathways. Dic substantially reduced the levels of Th2 cytokines, mucin 5AC in BALF, and OVA-specific IgE in the serum. Histology indicated reduced inflammatory cell infiltration, bronchial wall thickening, and peribronchial fibrosis in Dic-treated mice. Dic downregulated TGF-\u03b2 and p-Smad2\/3 expression and upregulated ZO-1 expression in the lung tissue. Dic downregulated TGF-\u03b2-induced Smad2\/3 phosphorylation in bronchial epithelial cells. Network pharmacology indicated enrichment of Dic-related genes in the TGF-\u03b2 pathway. Dic exhibited anti-asthmatic effects and is a potential therapeutic candidate.<\/jats:p>","DOI":"10.3390\/ijms262411891","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T12:20:57Z","timestamp":1765369257000},"page":"11891","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dictamnine Exhibits Anti-Asthmatic Effects by Modulating TGF-\u03b2\/Smad2\/3 Signaling in a Murine Asthma Model and Human Bronchial Epithelial Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3132-7308","authenticated-orcid":false,"given":"Myung-A","family":"Jung","sequence":"first","affiliation":[{"name":"KM Convergence Research Division, Korean Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bu-Yeo","family":"Kim","sequence":"additional","affiliation":[{"name":"KM Convergence Research Division, Korean Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8761-5187","authenticated-orcid":false,"given":"Joo Young","family":"Lee","sequence":"additional","affiliation":[{"name":"KM Convergence Research Division, Korean Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3992-8925","authenticated-orcid":false,"given":"Kon-Young","family":"Ji","sequence":"additional","affiliation":[{"name":"KM Convergence Research Division, Korean Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Han","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Infrastructure Team, R&D Strategy Division, Korean Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6250-5720","authenticated-orcid":false,"given":"Dong Ho","family":"Jung","sequence":"additional","affiliation":[{"name":"KM Convergence Research Division, Korean Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mudan","family":"Cai","sequence":"additional","affiliation":[{"name":"KM Science Research Division, Korean Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7503-9725","authenticated-orcid":false,"given":"Taesoo","family":"Kim","sequence":"additional","affiliation":[{"name":"KM Convergence Research Division, Korean Institute of Oriental Medicine, Daejeon 34054, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","unstructured":"GBD 2019 Chronic Respiratory Diseases Collaborators (2023). Global burden of chronic respiratory diseases and risk factors, 1990\u20132019: An update from the Global Burden of Disease Study 2019. EClinicalMedicine, 59, 101936."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S2213-2600(22)00496-9","article-title":"Advancement of asthma management in the past decade","volume":"11","author":"Fleming","year":"2023","journal-title":"Lancet Respir. Med."},{"key":"ref_3","first-page":"343","article-title":"Icariin alleviates transforming growth factor-\u03b21-induced epithelial-mesenchymal transition by targeting Smad and MAPK signaling pathways","volume":"12","author":"Li","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Frey, A., Lunding, L.P., Ehlers, J.C., Weckmann, M., Zissler, U.M., and Wegmann, M. (2020). More than just a barrier: The immune functions of the airway epithelium in asthma pathogenesis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00761"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.jaci.2006.07.012","article-title":"Mechanisms of airway hyperresponsiveness","volume":"118","author":"Cockcroft","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/j.rmed.2014.08.008","article-title":"Transforming growth factor \u03b2 and severe asthma: A perfect storm","volume":"108","author":"Hassan","year":"2014","journal-title":"Respir. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"110235","DOI":"10.1016\/j.cbi.2022.110235","article-title":"Amygdalin alleviated TGF-\u03b2-induced epithelial-mesenchymal transition in bronchial epithelial cells","volume":"369","author":"Zhang","year":"2023","journal-title":"Chem. Biol. Interact."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1183\/09031936.06.00130004","article-title":"The contribution of transforming growth factor-beta and epidermal growth factor signalling to airway remodelling in chronic asthma","volume":"27","author":"Boxall","year":"2006","journal-title":"Eur. Respir. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.bbrc.2014.02.051","article-title":"Interleukin-13-induced MUC5AC expression is regulated by a PI3K-NFAT3 pathway in mouse tracheal epithelial cells","volume":"446","author":"Yan","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1097\/ACI.0000000000000549","article-title":"Biological treatments for severe asthma","volume":"19","author":"Assaf","year":"2019","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"285","DOI":"10.2500\/108854198778557692","article-title":"Intranasal budesonide aqueous pump spray (Rhinocort Aqua) for the treatment of seasonal allergic rhinitis. Rhinocort Aqua Study Group","volume":"19","author":"Creticos","year":"1998","journal-title":"Allergy Asthma Proc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17534666251319175","DOI":"10.1177\/17534666251319175","article-title":"Adverse effects of biologics used to treat asthma","volume":"19","author":"Sitek","year":"2025","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"116319","DOI":"10.1016\/j.biopha.2024.116319","article-title":"Dictamnus dasycarpus Turcz. attenuates airway inflammation and mucus hypersecretion by modulating the STAT6-STAT3\/FOXA2 pathway","volume":"173","author":"Jung","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.jconrel.2020.10.007","article-title":"Dictamnine delivered by PLGA nanocarriers ameliorated inflammation in an oxazolone-induced dermatitis mouse model","volume":"329","author":"Lin","year":"2021","journal-title":"J. Control Release"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.cbi.2018.09.014","article-title":"Dictamnine promotes apoptosis and inhibits epithelial-mesenchymal transition, migration, invasion and proliferation by downregulating the HIF-1\u03b1 and Slug signaling pathways","volume":"296","author":"Wang","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1007\/s00210-023-02678-0","article-title":"Echinochrome exhibits anti-asthmatic activity through the suppression of airway inflammation, oxidative stress, and histopathological alterations in ovalbumin-induced asthma in BALB\/c mice","volume":"397","author":"Abdelmawgood","year":"2024","journal-title":"Arch. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e02864","DOI":"10.1016\/j.heliyon.2019.e02864","article-title":"An experimental model of asthma in rats using ovalbumin and lipopolysaccharide allergens","volume":"5","author":"Thakur","year":"2019","journal-title":"Heliyon"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4236","DOI":"10.1002\/ptr.7904","article-title":"Anti-inflammatory effect of dictamnine on allergic rhinitis via suppression of the LYN kinase-mediated molecular signaling pathway during mast cell activation","volume":"37","author":"Liu","year":"2023","journal-title":"Phytother. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1165\/ajrcmb.26.2.4600","article-title":"The Th2 lymphocyte products IL-4 and IL-13 rapidly induce airway hyperresponsiveness through direct effects on resident airway cells","volume":"26","author":"Venkayya","year":"2002","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1111\/all.14421","article-title":"Epithelial cell dysfunction, a major driver of asthma development","volume":"75","author":"Heijink","year":"2020","journal-title":"Allergy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e12172","DOI":"10.1002\/clt2.12172","article-title":"New insights into the regulation of TGF-\u03b2\/Smad and MPK signaling pathway gene expressions by nasal allergen and methacholine challenge test in asthma","volume":"12","author":"Panek","year":"2022","journal-title":"Clin. Transl. Allergy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jchromb.2013.10.025","article-title":"Pharmacokinetics, tissue distribution and excretion study of dictamnine, a major bioactive component from the root bark of Dictamnus dasycarpus Turz. (Rutaceae)","volume":"942\u2013943","author":"Wang","year":"2013","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Corteling, R., and Trifilieff, A. (2004). Gender comparison in a murine model of allergen-driven airway inflammation and the response to budesonide treatment. BMC Pharmacol., 4.","DOI":"10.1186\/1471-2210-4-4"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ekpruke, C.D., and Silveyra, P. (2022). Sex differences in airway remodeling and inflammation: Clinical and biological factors. Front. Allergy, 3.","DOI":"10.3389\/falgy.2022.875295"},{"key":"ref_25","first-page":"e3771","article-title":"Murine model of allergen induced asthma","volume":"63","author":"Reddy","year":"2012","journal-title":"J. Vis. Exp."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/gb-2003-4-5-p3","article-title":"DAVID: Database for annotation, visualization, and integrated discovery","volume":"4","author":"Dennis","year":"2003","journal-title":"Genome Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11891\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T12:22:49Z","timestamp":1765369369000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,10]]},"references-count":26,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262411891"],"URL":"https:\/\/doi.org\/10.3390\/ijms262411891","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,10]]}}}