{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:47:52Z","timestamp":1761709672542,"version":"3.41.2"},"reference-count":36,"publisher":"Portland Press Ltd.","issue":"2","license":[{"start":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T00:00:00Z","timestamp":1581638400000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,2,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background\/Aims: Recently, effective and purified ingredients of traditional Chinese medicine (TCM) were extracted to play crucial roles in the treatment of pulmonary diseases. Our previous research focused on TCM drug screening aimed at abnormal airway muscle contraction during respiratory diseases. Coptisine, an effective ingredient extracted from bitter herbs has shown a series of antioxidant, antibacterial, cardioprotective and neuroprotective pharmacological properties. In the current study, we questioned whether coptisine could also participate in asthma treatment through relaxing abnormal contracted mouse airway smooth muscle (ASM). The present study aimed to characterize the relaxant effects of coptisine on mouse ASM and uncover the underlying molecular mechanisms. Methods: To investigate the role of coptisine on pre-contracted mouse ASM, a series of biological techniques, including force measurement and patch-clamp experiments were employed. Results: Coptisine was found to inhibit high K+ or acetylcholine chloride (ACh)-induced pre-contracted mouse tracheal rings in a dose-dependent manner. Further research demonstrated that the coptisine-induced mouse ASM relaxation was mediated by alteration of calcium mobilization via voltage-dependent L-type Ca2+ channels (VDLCCs) and non-selective cation channels (NSCCs). Conclusion: Our data showed that mouse ASM could be relaxed by coptisine via altering the intracellular Ca2+ concentration through blocking VDLCCs and NSCCs, which suggested that this pharmacological active constituent might be classified as a potential new drug for the treatment of abnormal airway muscle contraction.<\/jats:p>","DOI":"10.1042\/bsr20190534","type":"journal-article","created":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T11:33:57Z","timestamp":1581680037000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Coptisine, a protoberberine alkaloid, relaxes mouse airway smooth muscle via blockade of VDLCCs and NSCCs"],"prefix":"10.1042","volume":"40","author":[{"given":"Nana","family":"Wen","sequence":"first","affiliation":[{"name":"Institute For Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Xue","sequence":"additional","affiliation":[{"name":"Institute For Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongle","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute For Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunbo","family":"Shi","sequence":"additional","affiliation":[{"name":"Institute For Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing-Hua","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute For Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Congli","family":"Cai","sequence":"additional","affiliation":[{"name":"Wuhan Youzhiyou Biopharmaceutical Co., Ltd., 666 Gaoxin Rd, Biolake, Wuhan 430075, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6795-4501","authenticated-orcid":false,"given":"Jinhua","family":"Shen","sequence":"additional","affiliation":[{"name":"Institute For Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2020,2,25]]},"reference":[{"key":"2021111620031069900_B1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s40248-016-0040-9","article-title":"Health-related quality of life measurement in asthma and chronic obstructive pulmonary disease: review of the 2009-2014 literature","volume":"11","author":"Arpinelli","year":"2015","journal-title":"Multidiscip. Respir. Med."},{"key":"2021111620031069900_B2","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1038\/nm.2237","article-title":"Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction","volume":"16","author":"Deshpande","year":"2010","journal-title":"Nat. Med."},{"key":"2021111620031069900_B3","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1177\/2040622315609251","article-title":"Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease","volume":"7","author":"George","year":"2016","journal-title":"Ther. Adv. Chronic Dis."},{"key":"2021111620031069900_B4","doi-asserted-by":"publisher","first-page":"L1125","DOI":"10.1152\/ajplung.00154.2014","article-title":"Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells","volume":"308","author":"Shkumatov","year":"2015","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"2021111620031069900_B5","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/j.jaci.2015.01.046","article-title":"Oxidative stress-induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease","volume":"136","author":"Wiegman","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"2021111620031069900_B6","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/S0163-7258(00)00039-5","article-title":"Traditional Chinese medicine: an approach to scientific proof and clinical validation","volume":"86","author":"Yuan","year":"2000","journal-title":"Pharmacol. Ther."},{"key":"2021111620031069900_B7","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s12906-017-1674-7","article-title":"Nelumbo nucifera leaves extracts inhibit mouse airway smooth muscle contraction","volume":"17","author":"Yang","year":"2017","journal-title":"BMC Complement. Altern. Med."},{"key":"2021111620031069900_B8","doi-asserted-by":"publisher","first-page":"3114","DOI":"10.1038\/s41598-018-20409-x","article-title":"Polygonum aviculare L. extract and quercetin attenuate contraction in airway smooth muscle","volume":"8","author":"Luo","year":"2018","journal-title":"Sci. Rep."},{"key":"2021111620031069900_B9","doi-asserted-by":"publisher","first-page":"731","DOI":"10.3389\/fpls.2018.00731","article-title":"Identification and characterization of genes involved in benzylisoquinoline alkaloid biosynthesis in Coptis species","volume":"9","author":"He","year":"2018","journal-title":"Front. Plant Sci."},{"key":"2021111620031069900_B10","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/j.1440-1681.2004.03951.x","article-title":"Cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents (berberine, coptisine and icariin) on hepatoma and leukaemia cell growth","volume":"31","author":"Lin","year":"2004","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"2021111620031069900_B11","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1055\/s-2006-957576","article-title":"Antispasmodic and relaxant activity of chelidonine, protopine, coptisine, and Chelidonium majus extracts on isolated guinea-pig ileum","volume":"64","author":"Hiller","year":"1998","journal-title":"Planta Med."},{"key":"2021111620031069900_B12","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1080\/14786419.2013.867344","article-title":"Facile synthesis of tetrahydroprotoberberine and protoberberine alkaloids from protopines and study on their antibacterial activities","volume":"28","author":"Cheng","year":"2014","journal-title":"Nat. Prod. Res."},{"key":"2021111620031069900_B13","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3233\/JAD-140414","article-title":"The IDO inhibitor coptisine ameliorates cognitive impairment in a mouse model of Alzheimer\u2019s disease","volume":"43","author":"Yu","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"2021111620031069900_B14","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.atherosclerosis.2012.01.046","article-title":"Coptisine exert cardioprotective effect through anti-oxidative and inhibition of RhoA\/Rho kinase pathway on isoproterenol-induced myocardial infarction in rats","volume":"222","author":"Gong","year":"2012","journal-title":"Atherosclerosis"},{"key":"2021111620031069900_B15","doi-asserted-by":"publisher","first-page":"827308","DOI":"10.1155\/2015\/827308","article-title":"Neuroprotective activity of coptisine from Coptis chinensis (Franch)","volume":"2015","author":"Friedemann","year":"2015","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"2021111620031069900_B16","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.1159\/000475653","article-title":"Relaxing effect of TSU-68, an antiangiogenic agent, on mouse airway smooth muscle","volume":"41","author":"Tan","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"2021111620031069900_B17","doi-asserted-by":"publisher","first-page":"523640","DOI":"10.1155\/2015\/523640","article-title":"Relaxant action of plumula nelumbinis extract on mouse airway smooth muscle","volume":"2015","author":"Tan","year":"2015","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"2021111620031069900_B18","doi-asserted-by":"publisher","first-page":"e101578","DOI":"10.1371\/journal.pone.0101578","article-title":"Non-selective cation channels mediate chloroquine-induced relaxation in precontracted mouse airway smooth muscle","volume":"9","author":"Zhang","year":"2014","journal-title":"PLoS ONE"},{"key":"2021111620031069900_B19","doi-asserted-by":"publisher","first-page":"11418","DOI":"10.1073\/pnas.0813307106","article-title":"Membrane depolarization causes a direct activation of G protein-coupled receptors leading to local Ca2+ release in smooth muscle","volume":"106","author":"Liu","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111620031069900_B20","first-page":"157","article-title":"Calcium movements, distribution, and functions in smooth muscle","volume":"49","author":"Karaki","year":"1997","journal-title":"Pharmacol. Rev."},{"key":"2021111620031069900_B21","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1540\/jsmr1965.20.427","article-title":"Potassium-induced contraction in smooth muscle","volume":"20","author":"Karaki","year":"1984","journal-title":"Nihon Heikatsukin Gakkai Zasshi"},{"key":"2021111620031069900_B22","first-page":"782","article-title":"Inhibition of bronchoconstriction in the guinea pig by a calcium channel blocker, nifedipine","volume":"125","author":"Darnell","year":"1982","journal-title":"Am. Rev. Respir. Dis."},{"key":"2021111620031069900_B23","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1142\/S0192415X12500243","article-title":"Analysis of the mechanisms underlying the vasorelaxant action of coptisine in rat aortic rings","volume":"40","author":"Gong","year":"2012","journal-title":"Am. J. Chin. Med."},{"key":"2021111620031069900_B24","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1038\/sj.bjp.0705615","article-title":"Effects of chloride channel blockers on hypotonicity-induced contractions of the rat trachea","volume":"141","author":"Coelho","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"2021111620031069900_B25","doi-asserted-by":"publisher","first-page":"E4706","DOI":"10.1073\/pnas.1406029111","article-title":"VEGF-induced neoangiogenesis is mediated by NAADP and two-pore channel-2-dependent Ca2+ signaling","volume":"111","author":"Favia","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111620031069900_B26","doi-asserted-by":"publisher","first-page":"C341","DOI":"10.1152\/ajpcell.1997.272.1.C341","article-title":"Muscarinic activation and calcium permeation of nonselective cation currents in airway myocytes","volume":"272","author":"Fleischmann","year":"1997","journal-title":"Am. J. Physiol."},{"key":"2021111620031069900_B27","doi-asserted-by":"publisher","first-page":"C500","DOI":"10.1152\/ajpcell.1997.273.2.C500","article-title":"M2 receptor activation of nonselective cation channels in smooth muscle cells: calcium and Gi\/G(o) requirements","volume":"273","author":"Wang","year":"1997","journal-title":"Am. J. Physiol."},{"key":"2021111620031069900_B28","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.jash.2008.09.002","article-title":"Vascular smooth muscle cell signaling mechanisms for contraction to angiotensin II and endothelin-1","volume":"3","author":"Wynne","year":"2009","journal-title":"J. Am. Soc. Hypertens."},{"key":"2021111620031069900_B29","doi-asserted-by":"publisher","first-page":"8703239","DOI":"10.1155\/2016\/8703239","article-title":"Cortex phellodendri extract relaxes airway smooth muscle","volume":"2016","author":"Jiang","year":"2016","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"2021111620031069900_B30","doi-asserted-by":"publisher","first-page":"9872302","DOI":"10.1155\/2016\/9872302","article-title":"Bioactive natural molecules and traditional herbal medicine in the treatment of airways diseases","volume":"2016","author":"Rogerio","year":"2016","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"2021111620031069900_B31","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-01312-1_3","article-title":"Transient receptor potential and orai channels in airway smooth muscle cells","volume-title":"Calcium Signaling In Airway Smooth Muscle Cells","author":"Xiao","year":"2014"},{"key":"2021111620031069900_B32","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s00424-013-1405-y","article-title":"Sodium-calcium exchangers (NCX): molecular hallmarks underlying the tissue-specific and systemic functions","volume":"466","author":"Khananshvili","year":"2014","journal-title":"Pflugers Arch."},{"key":"2021111620031069900_B33","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1002\/mus.20731","article-title":"Sources of axonal calcium loading during in vitro ischemia of rat dorsal roots","volume":"35","author":"Petrescu","year":"2007","journal-title":"Muscle Nerve"},{"key":"2021111620031069900_B34","first-page":"H1868","article-title":"Cardioprotective effects of KB-R7943: a novel inhibitor of the reverse mode of Na+\/Ca2+ exchanger","volume":"276","author":"Ladilov","year":"1999","journal-title":"Am. J. Physiol."},{"key":"2021111620031069900_B35","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.jep.2005.05.010","article-title":"Antispasmodic and blood pressure lowering effects of Valeriana wallichii are mediated through K+ channel activation","volume":"100","author":"Gilani","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"2021111620031069900_B36","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.ejphar.2011.08.013","article-title":"Large conductance Ca2+-activated K+ channel activation with NS1619 decreases myogenic and neurogenic contractions of rat detrusor smooth muscle","volume":"670","author":"Soder","year":"2011","journal-title":"Eur. J. Pharmacol."}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20190534\/868397\/bsr-2019-0534.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20190534\/868397\/bsr-2019-0534.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T20:41:20Z","timestamp":1637095280000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/40\/2\/BSR20190534\/222118\/Coptisine-a-protoberberine-alkaloid-relaxes-mouse"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2,28]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20190534","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"type":"print","value":"0144-8463"},{"type":"electronic","value":"1573-4935"}],"subject":[],"published-other":{"date-parts":[[2020,2]]},"published":{"date-parts":[[2020,2]]},"article-number":"BSR20190534"}}