{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T13:09:31Z","timestamp":1793279371446,"version":"4.5.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Allergic asthma is a stubborn chronic inflammatory disease, and is considered a co-result of various immune cells, especially mast cells, eosinophils and T lymphocytes. At present, the treatment methods of allergic asthma are limited and the side effects are obvious. Traditional Chinese medicine has been used to treat diseases for thousands of years in China. One such example is the treatment of allergic asthma, which take the characteristics of less adverse reactions and obvious curative effect. Tuo-Min-Ding-Chuan Decoction (TMDCD) is a traditional Chinese medicine compound for the treatment of allergic asthma optimized from Ma-Xing-Gan-Shi Decoction (MXGSD), which was put forward in Treatise on Febrile Diseases by Zhang Zhongjing in the Eastern Han Dynasty. The compound shows a significant clinical effect, but the mechanism of its influence on the immune system is still unclear. The purpose of this study was to observe whether TMDCD could alleviate the symptoms of ovalbumin (OVA) challenged allergic asthma mice, and to explore its immune regulatory mechanism, especially on mast cell (MC) degranulation. The results showed TMDCD could not only reduce the airway hyperresponsiveness (AHR), inflammatory cell infiltration and mucus secretion in the lung tissue of OVA challenged mice, but also decrease the levels of total IgE, OVA-specific IgE, histamine and LTC4 in serum. We found that TMDCD can downregulate the expression of Fractalkine, Tryptase \u03b5, IL-25, CCL19, MCP-1, OX40L, Axl, CCL22, CD30, G-CSF, E-selectin, OPN, CCL5, P-selectin, Gas6, TSLP in OVA challenged mice serum by using mouse cytokines antibody array. It has been reported in some literatures that these differentially expressed proteins are related to the occurrence of allergic asthma, such as tryptase \u03b5, MCP-1, CCL5, etc. can be released by MC. And the results of <jats:italic>in vitro<\/jats:italic> experiments showed that TMDCD inhibited the degranulation of RBL-2H3 cells stimulated by DNP-IgE\/BSA. Taken together, we made the conclusion that TMDCD could reduce the infiltration of inflammatory cells in lung tissue and alleviate airway remodeling in mice with allergic asthma, showed the effects of anti-inflammatory and antiasthmatic. TMDCD could also reduce the levels of IgE, histamine, LTC4, Tryptase \u03b5, and other MC related proteins in the serum of allergic asthma mice, and the <jats:italic>in vitro<\/jats:italic> experiments showed that TMDCD could inhibit IgE mediated degranulation and histamine release of RBL-2H3 cells, proved its anti allergic effect.<\/jats:p>","DOI":"10.3389\/fphar.2021.725953","type":"journal-article","created":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T08:36:13Z","timestamp":1632299773000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Tuo-Min-Ding-Chuan Decoction Alleviate Ovalbumin-Induced Allergic Asthma by Inhibiting Mast Cell Degranulation and Down-Regulating the Differential Expression Proteins"],"prefix":"10.3389","volume":"12","author":[{"given":"Jingbo","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingsheng","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeqiang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghe","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"B1","first-page":"141","volume-title":"Study on the Expression of Eosinophil-Related Factors in Allergic Constitution and the Intervention Mechanism of Guominkang","author":"Bao","year":"2017"},{"key":"B2","doi-asserted-by":"publisher","first-page":"172760","DOI":"10.1016\/j.ejphar.2019.172760","article-title":"IL-33 Stimulates Human Mast Cell Release of CCL5 and CCL2 via MAPK and NF-\u039ab, Inhibited by Methoxyluteolin","volume":"865","author":"Bawazeer","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1152\/jappl.2001.91.3.1372","article-title":"Tryptase and Agonists of PAR-2 Induce the Proliferation of Human Airway Smooth Muscle Cells","volume":"91","author":"Berger","year":"2001","journal-title":"J. Appl. Physiol. (1985)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.12669\/pjms.345.15334","article-title":"Changes and Correlations of Serum Interleukins, Adhesion Molecules and Soluble E-Selectin in Children with Allergic Rhinitis and Asthma","volume":"34","author":"Bi","year":"2018","journal-title":"Pak. J. Med. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1111\/cea.12675","article-title":"Mast Cells in Asthma-Sstate of the Art","volume":"46","author":"Bradding","year":"2016","journal-title":"Clin. Exp. Allergy"},{"key":"B6","doi-asserted-by":"publisher","first-page":"255","DOI":"10.13193\/j.issn.1673-7717.2020.10.060","article-title":"Clinical Efficacy of Modified Maxing Shigan Decoction Combined with Montelukast Sodium in Children with Bronchial Asthma","volume":"38","author":"Cai","year":"2020","journal-title":"Chin. Arch. Traditional Chin. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3124","DOI":"10.1111\/all.14607","article-title":"Advances and Recent Developments in Asthma in 2020","volume":"75","author":"Cevhertas","year":"2020","journal-title":"Allergy"},{"key":"B8","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/j.1365-2249.2009.03998.x","article-title":"Cytokine and Anti-cytokine Therapy in Asthma: Ready for the Clinic?","volume":"158","author":"Desai","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1089\/jir.2008.0027","article-title":"Monocyte Chemoattractant Protein-1 (MCP-1): an Overview","volume":"29","author":"Deshmane","year":"2009","journal-title":"J. Interferon Cytokine Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1111\/resp.13935","article-title":"Challenges Faced in Managing Adult Asthma: A Perspective from Asian Countries","volume":"25","author":"Dhar","year":"2020","journal-title":"Respirology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1111\/j.1600-0625.2010.01073.x","article-title":"Immature Mast Cells Exhibit Rolling and Adhesion to Endothelial Cells and Subsequent Diapedesis Triggered by E- and P-Selectin, VCAM-1 and PECAM-1","volume":"19","author":"Dudeck","year":"2010","journal-title":"Exp. Dermatol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1007\/s12016-018-8720-1","article-title":"Mast Cell-Mediated Orchestration of the Immune Responses in Human Allergic Asthma: Current Insights","volume":"56","author":"Elieh Ali Komi","year":"2019","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","article-title":"The PI3K Pathway in Human Disease","volume":"170","author":"Fruman","year":"2017","journal-title":"Cell"},{"key":"B14","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/nm.2755","article-title":"IgE and Mast Cells in Allergic Disease","volume":"18","author":"Galli","year":"2012","journal-title":"Nat. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s11882-005-0090-0","article-title":"New Chemokine Targets for Asthma Therapy","volume":"5","author":"Garcia","year":"2005","journal-title":"Curr. Allergy Asthma Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1111\/all.12927","article-title":"Protein Profiles of CCL5, HPGDS, and NPSR1 in Plasma Reveal Association with Childhood Asthma","volume":"71","author":"Hamsten","year":"2016","journal-title":"Allergy"},{"key":"B18","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1006\/smim.1998.0156","article-title":"CD30: Expression and Function in Health and Disease","volume":"10","author":"Horie","year":"1998","journal-title":"Semin. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3389\/fmed.2020.00191","article-title":"Airway Remodeling in Asthma","volume":"7","author":"Hough","year":"2020","journal-title":"Front. Med. (Lausanne)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/S0140-6736(19)31147-X","article-title":"Prevalence, Risk Factors, and Management of Asthma in China: a National Cross-Sectional Study","volume":"394","author":"Huang","year":"2019","journal-title":"Lancet"},{"key":"B21","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1159\/000509600","article-title":"Plasma P-Selectin Is Inversely Associated with Lung Function and Corticosteroid Responsiveness in Asthma","volume":"181","author":"Johansson","year":"2020","journal-title":"Int. Arch. Allergy Immunol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1159\/000312127","article-title":"Serum Eosinophil Cationic Protein and 27 Cytokines\/Chemokines in Acute Exacerbation of Childhood Asthma","author":"Kato","year":"2010","journal-title":"Int. Arch. Allergy Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1164\/rccm.200603-394OC","article-title":"Airway Smooth Muscle and Mast Cell-Derived CC Chemokine Ligand 19 Mediate Airway Smooth Muscle Migration in Asthma","volume":"174","author":"Kaur","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1016\/j.jaci.2019.07.029","article-title":"TNF-\u03b1-induced Protein 3 Is a Key Player in Childhood Asthma Development and Environment-Mediated protection","volume":"144","author":"Krusche","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/j.immuni.2019.03.018","article-title":"The Cytokines of Asthma","volume":"50","author":"Lambrecht","year":"2019","journal-title":"Immunity"},{"key":"B26","doi-asserted-by":"publisher","first-page":"4178","DOI":"10.3390\/molecules25184178","article-title":"Extract of Boehmeria Nivea Suppresses Mast Cell-Mediated Allergic Inflammation by Inhibiting Mitogen-Activated Protein Kinase and Nuclear Factor-\u039ab","volume":"25","author":"Lim","year":"2020","journal-title":"Molecules"},{"key":"B27","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1159\/000242355","article-title":"The Role of Costimulatory Molecules in Allergic Disease and Asthma","volume":"151","author":"Lombardi","year":"2010","journal-title":"Int. Arch. Allergy Immunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"148","DOI":"10.11656\/j.issn.1672-1519.2019.02.13","article-title":"Clinical Research on Treating Acute Bronchial Asthma of Evil Heat Obstructing Lung with Maxing Shigan Decoction Combined with Conventional Therapy","volume":"36","author":"Ma","year":"2019","journal-title":"Tianjin J. Traditional Chin. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/s41533-020-00192-x","article-title":"Association of Low-Dosage Systemic Corticosteroid Use with Disease burden in Asthma","volume":"30","author":"Matsunaga","year":"2020","journal-title":"NPJ Prim. Care Respir. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"569","DOI":"10.3949\/ccjm.87a.19136","article-title":"Managing Adult Asthma: The 2019 GINA Guidelines","volume":"87","author":"Mauer","year":"2020","journal-title":"Cleve Clin. J. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/imr.12634","article-title":"Mast Cells as Sources of Cytokines, Chemokines, and Growth Factors","volume":"282","author":"Mukai","year":"2018","journal-title":"Immunol. Rev."},{"key":"B32","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1002\/eji.200737057","article-title":"Osteopontin Is Produced by Mast Cells and Affects IgE-Mediated Degranulation and Migration of Mast Cells","volume":"38","author":"Nagasaka","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1080\/14656566.2020.1807514","article-title":"Advances with Glucocorticoids in the Treatment of Asthma: State of the Art","volume":"21","author":"Ora","year":"2020","journal-title":"Expert Opin. Pharmacother."},{"key":"B34","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1159\/000513582","article-title":"Novel Strategies to Target Mast Cells in Disease","volume":"13","author":"Paivandy","year":"2021","journal-title":"J. Innate Immun."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20193899","article-title":"Galectin-1 Inhibits PDGF-BB-Induced Proliferation and Migration of Airway Smooth Muscle Cells through the Inactivation of PI3K\/Akt Signaling Pathway","volume":"40","author":"Pang","year":"2020","journal-title":"Biosci. Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2001337","DOI":"10.1183\/13993003.01337-2020","article-title":"Mast Cells in Asthma: Here I Am, Stuck in the Middle with You","volume":"56","author":"Penn","year":"2020","journal-title":"Eur. Respir. J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1016\/j.jaci.2006.07.014","article-title":"Direct Evidence for a Critical Role of CD30 in the Development of Allergic Asthma","volume":"118","author":"Polte","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"193","DOI":"10.2147\/JAA.S176026","article-title":"Adverse Outcomes from Initiation of Systemic Corticosteroids for Asthma: Long-Term Observational Study","volume":"11","author":"Price","year":"2018","journal-title":"J. Asthma Allergy"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e3771","DOI":"10.3791\/3771","article-title":"Murine Model of Allergen Induced Asthma","author":"Reddy","year":"2012","journal-title":"J. Vis. Exp."},{"key":"B40","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1111\/cea.13388","article-title":"Circulating Mast Cell Progenitors Correlate with Reduced Lung Function in Allergic Asthma","volume":"49","author":"Salomonsson","year":"2019","journal-title":"Clin. Exp. Allergy"},{"key":"B41","doi-asserted-by":"publisher","first-page":"4068","DOI":"10.1002\/jcp.27201","article-title":"MicroRNA-133a Alleviates Airway Remodeling in Asthtama through PI3K\/AKT\/mTOR Signaling Pathway by Targeting IGF1R","volume":"234","author":"Shao","year":"2019","journal-title":"J. Cel. Physiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"17362","DOI":"10.1038\/s41598-018-35791-9","article-title":"Uncovering the Mechanism of Maxing Ganshi Decoction on Asthma from a Systematic Perspective: A Network Pharmacology Study","volume":"8","author":"Song","year":"2018","journal-title":"Sci. Rep."},{"key":"B43","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.cyto.2013.03.014","article-title":"The Activation and Regulation of IL-17 Receptor Mediated Signaling","volume":"62","author":"Song","year":"2013","journal-title":"Cytokine"},{"key":"B16","year":"2018"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1016\/j.jaci.2018.02.032","article-title":"Regulation of Type 2 Innate Lymphoid Cell-dependent Airway Hyperreactivity by Butyrate","volume":"142","author":"Thio","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"e83","DOI":"10.1016\/j.ddmec.2012.09.003","article-title":"TSLP: A Key Regulator of Asthma Pathogenesis","volume":"9","author":"West","year":"2012","journal-title":"Drug Discov. Today Dis. Mech."},{"key":"B51","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.bbrc.2005.08.137","article-title":"Identification of a Subgroup of Glycosylphosphatidylinositol-Anchored Tryptases","volume":"336","author":"Wong","year":"2005","journal-title":"Biochem. Bioph. Res. Co."},{"key":"B46","doi-asserted-by":"publisher","first-page":"4322","DOI":"10.19540\/j.cnki.cjcmm.20190629.308","article-title":"Study on Famous Prescription of Prestigious Traditional Chinese Medicine Based on QbD Concept: Optimization of Extraction Process and Granule Forming Process of Tuomin Dingchuan Prescription","volume":"44","author":"Wu","year":"2019","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"B47","doi-asserted-by":"publisher","first-page":"588588","DOI":"10.3389\/fphar.2021.588588","article-title":"iTRAQ-Based Proteomics Reveals Gu-Ben-Fang-Xiao Decoction Alleviates Airway Remodeling via Reducing Extracellular Matrix Deposition in a Murine Model of Chronic Remission Asthma","volume":"12","author":"Xing","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"3513","DOI":"10.1177\/0300060519860684","article-title":"Association between Osteopontin Expression and Asthma: a Meta-Analysis","volume":"47","author":"Xu","year":"2019","journal-title":"J. Int. Med. Res."},{"key":"B49","first-page":"1883","article-title":"Expression of STAT4 in Asthma Rats Treated with Chinese Medicine Maxingshigan Decoction","volume":"39","author":"Yu","year":"2017","journal-title":"Zhejiang Med. J."},{"key":"B50","doi-asserted-by":"publisher","first-page":"e14525","DOI":"10.1371\/journal.pone.0014525","article-title":"Regulation of Endothelial Cell Adhesion Molecule Expression by Mast Cells, Macrophages, and Neutrophils","volume":"6","author":"Zhang","year":"2011","journal-title":"PLoS One"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.725953\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T08:36:21Z","timestamp":1632299781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.725953\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,22]]},"references-count":51,"alternative-id":["10.3389\/fphar.2021.725953"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.725953","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,22]]},"article-number":"725953"}}