{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T20:39:53Z","timestamp":1793479193529,"version":"4.5.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803545"],"award-info":[{"award-number":["81803545"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Asthma is a chronic and recurring airway disease, which related to mast cell activation. Many compounds derived from Chinese herbal medicine has promising effects on stabilizing mast cells and decreasing inflammatory mediator production. Safranal, one of the active compounds from <jats:italic>Crocus sativus<\/jats:italic>, shows many anti-inflammatory properties. In this study, we evaluated the effect of safranal in ovalbumin (OVA)-induced asthma model. Furthermore, we investigate the effectiveness of safranal on stabilizing mast cell and inhibiting the production of inflammatory mediators in passive systemic anaphylaxis (PSA) model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>OVA-induced asthma and PSA model were used to evaluate the effect of safranal <jats:italic>in vivo.<\/jats:italic> Lung tissues were collected for H&amp;amp;E, TB, IHC, and PAS staining. ELISA were used to determine level of IgE and chemokines (IL-4, IL-5, TNF-\u03b1, and IFN-\u03b3). RNA sequencing was used to uncovers genes that safranal regulate. Bone marrow-derived mast cells (BMMCs) were used to investigate the inhibitory effect and mechanism of safranal. Cytokine production (IL-6, TNF-\u03b1, and LTC<jats:sub>4<\/jats:sub>) and NF-\u03baB and MAPKs signaling pathway were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Safranal reduced the level of serum IgE, the number of mast cells in lung tissue were decreased and Th1\/Th2 cytokine levels were normalized in OVA-induced asthma model. Furthermore, safranal inhibited BMMCs degranulation and inhibited the production of LTC<jats:sub>4<\/jats:sub>, IL-6, and TNF-\u03b1. Safranal inhibits NF-\u03baB and MAPKs pathway protein phosphorylation and decreases NF-\u03baB p65, AP-1 nuclear translocation. In the PSA model, safranal reduced the levels of histamine and LTC<jats:sub>4<\/jats:sub> in serum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Safranal alleviates OVA-induced asthma, inhibits mast cell activation and PSA reaction. The possible mechanism occurs through the inhibition of the MAPKs and NF-\u03baB pathways.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.585595","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T05:56:13Z","timestamp":1621490173000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":59,"title":["Safranal Alleviated OVA-Induced Asthma Model and Inhibits Mast Cell Activation"],"prefix":"10.3389","volume":"12","author":[{"given":"Peeraphong","family":"Lertnimitphun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwei","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baican","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changwu","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhong","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1471-2466-6-13","article-title":"Attitudes and Actions of Asthma Patients on Regular Maintenance Therapy: The INSPIRE Study","volume":"6","author":"Partridge","year":"2006","journal-title":"BMC Pulm Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801285R","article-title":"Il-13 Signaling Through IL-13 Receptor Alpha2 Mediates Airway Epithelial Wound Repair","volume":"33","author":"Yang","year":"2019","journal-title":"FASEB J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2001.01177.x","article-title":"Local Increase in the Number of Mast Cells and Expression of Nerve Growth Factor in the Bronchus of Asthmatic Patients After Repeated Inhalation of Allergen At Low-Dose","volume":"31","author":"Kassel","year":"2001","journal-title":"Clin Exp Allergy"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.2009.03771.x","article-title":"Efficacy of a 5-HT1a Receptor Agonist in Atopic Dermatitis","volume":"35","author":"Kawana","year":"2010","journal-title":"Clin Exp Dermatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"112136","DOI":"10.1016\/j.jep.2019.112136","article-title":"Total Glucosides of Peony Improve Ovalbumin-Induced Allergic Asthma by Inhibiting Mast Cell Degranulation","volume":"244","author":"Shou","year":"2019","journal-title":"J Ethnopharmacol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.01.049","article-title":"Humanized Mouse Model of Mast Cell-Mediated Passive Cutaneous Anaphylaxis and Passive Systemic Anaphylaxis","volume":"138","author":"Bryce","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.4937","article-title":"Inflammation and Airway Remodeling of the Lung in Guinea Pigs With Allergic Rhinitis","volume":"14","author":"Chen","year":"2017","journal-title":"Exp Ther Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/all.13663","article-title":"Massive Release of the Histamine-Degrading Enzyme Diamine Oxidase During Severe Anaphylaxis in Mastocytosis Patients","volume":"74","author":"Boehm","year":"2019","journal-title":"Allergy"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-018-0329-9","article-title":"Safranal Protects Against Beta-Amyloid Peptide-Induced Cell Toxicity in PC12 Cells Via MAPK and PI3 K Pathways","volume":"34","author":"Rafieipour","year":"2019","journal-title":"Metab Brain Dis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.neulet.2017.08.065","article-title":"Anti-Oxidative Effects of Safranal on Immobilization-Induced Oxidative Damage in Rat Brain","volume":"659","author":"Samarghandian","year":"2017","journal-title":"Neurosci Lett"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5315","article-title":"Safranal of Crocus Sativus L. 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