{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:14:00Z","timestamp":1792624440602,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Liaoning Province \u201cXing Liao Talents Program\u201d Project","award":["XLYC1805002"],"award-info":[{"award-number":["XLYC1805002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2022,5,9]]},"abstract":"<jats:p>Background. To investigate the beneficial effect of berberine on gastroesophageal reflux-induced airway hyperresponsiveness (GERAHR) and explore the underlying mechanism. Methods. Coword cluster analysis and strategic coordinates were used to identify hotspots for GERAHR research, and an online tool (STRING, https:\/\/string-db.org\/) was used to predict the potential relationships between proteins. Guinea pigs with chemically induced GERAHR received PBS or different berberine-based treatments to evaluate the therapeutic effect of berberine and characterize the underlying mechanism. Airway responsiveness was assessed using a plethysmography system, and protein expression was evaluated by western blotting, immunohistochemical staining, and quantitative PCR analysis. Results. Bioinformatics analyses revealed that TRP channels are hotspots of GERAHR research, and TRPA1 is related to the proinflammatory neuropeptide substance P (SP). Berberine, especially at the middle dose tested (MB, 150\u2009mg\/kg), significantly improved lung function, suppressed inflammatory cell infiltration, and protected inflammation-driven tissue damage in the lung, trachea, esophagus, and nerve tissues in GERAHR guinea pigs. MB reduced the expression of TRPA1, SP, and tumor necrosis factor-alpha (TNF-\u03b1) in evaluated organs and tissues. Meanwhile, the MB-mediated protective effects were attenuated by simultaneous TRPA1 activation. Conclusions. Mechanistically, berberine was found to suppress GERAHR-induced upregulation of TRPA1, SP, and TNF-\u03b1 in many tissues. Our study has highlighted the potential therapeutic value of berberine for the treatment of GERAHR.<\/jats:p>","DOI":"10.1155\/2022\/7464147","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T02:05:13Z","timestamp":1652148313000},"page":"1-14","source":"Crossref","is-referenced-by-count":5,"title":["Berberine Alleviates Gastroesophageal Reflux-Induced Airway Hyperresponsiveness in a Transient Receptor Potential A1-Dependent Manner"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3613-3089","authenticated-orcid":true,"given":"Bo","family":"Zou","sequence":"first","affiliation":[{"name":"Institute of Respiratory Diseases, The First Hospital of China Medical University, Shenyang City, Liaoning Province, China"},{"name":"Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4614-9738","authenticated-orcid":true,"given":"Chaofan","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Respiratory Diseases, The First Hospital of China Medical University, Shenyang City, Liaoning Province, China"},{"name":"Department of Respiratory Medicine, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0958-049X","authenticated-orcid":true,"given":"Yue","family":"Fu","sequence":"additional","affiliation":[{"name":"Institute of Respiratory Diseases, The First Hospital of China Medical University, Shenyang City, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2413-2951","authenticated-orcid":true,"given":"Dianzhu","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou City, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4418-7028","authenticated-orcid":true,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Respiratory Diseases, The First Hospital of China Medical University, Shenyang City, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9754-7026","authenticated-orcid":true,"given":"Lingfei","family":"Kong","sequence":"additional","affiliation":[{"name":"Institute of Respiratory Diseases, The First Hospital of China Medical University, Shenyang City, Liaoning Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1185\/030079905x38240"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1159\/000292650"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900591106"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-57936-5"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.148379"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.153585"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-012-9570-2"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.01.012"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.590261"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.02.033"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-008-9089-3"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1177\/2058738419866379"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117442"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.01851.x"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.12659\/msm.908950"},{"key":"16","article-title":"A new approach to identify research focus of medical informatics departments in China","volume":"35","author":"L. Cui","year":"2010","journal-title":"Geomatics and Information Science of Wuhan University"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1007\/bf02019280"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1007\/bf02019278"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0484oc"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b16-00280"},{"key":"22","article-title":"Assessment of respiratory function in conscious mice by double-chamber plethysmography","volume":"137","author":"S. Mailhot-Larouche","year":"2018","journal-title":"Journal of Visualized Experiments"},{"key":"23","article-title":"Bronchoalveolar lavage of murine lungs to analyze inflammatory cell infiltration","volume":"123","author":"L. Van Hoecke","year":"2017","journal-title":"Journal of Visualized Experiments"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-018-5216-z"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1042\/bsr20190440"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0189812"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.07.055"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-4-48"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/gou061"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.7150\/jca.44126"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.0c05591"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1513\/annalsats.201408-391oc"},{"issue":"6","key":"33","first-page":"8641","article-title":"Berberine attenuates cigarette smoke-induced airway inflammation and mucus hypersecretion in mice","volume":"8","author":"D. Xu","year":"2015","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13098"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.07.036"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-018-0675-z"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.07.019"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706197"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7450151"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201902627r"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m110.106153"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.133231"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00189.2019"}],"container-title":["Evidence-Based Complementary and Alternative Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2022\/7464147.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2022\/7464147.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2022\/7464147.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T02:05:21Z","timestamp":1652148321000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/ecam\/2022\/7464147\/"}},"subtitle":[],"editor":[{"given":"Qin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,5,9]]},"references-count":43,"alternative-id":["7464147","7464147"],"URL":"https:\/\/doi.org\/10.1155\/2022\/7464147","relation":{},"ISSN":["1741-4288","1741-427X"],"issn-type":[{"value":"1741-4288","type":"electronic"},{"value":"1741-427X","type":"print"}],"subject":[],"published":{"date-parts":[[2022,5,9]]}}}