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Thus, its mechanism of action was determined in an ex vivo tracheal rat ring bioassay. The anti\u2010asthmatic effect was assayed in in vivo OVAlbumin (OVA)\u2010sensitized guinea pigs. Finally, the toxicological profile of 6\u2010HOF was studied based on Organization of Economic Cooperation and Development guidelines with modifications. 6\u2010HOF\u2013induced relaxation appears to be related with receptor\u2010operated calcium channel and voltage\u2010operated calcium channel blockade as the main mechanism of action, and also through the production of relaxant second messengers NO and cGMP. Molecular docking supports that 6\u2010HOF acts as calcium channel blocker and by activation of nitric oxide synthase. In addition, the in vivo anti\u2010asthmatic experiments demonstrate the dose\u2010dependent significant anti\u2010allergic effect of 6\u2010HOF induced by OVA, with best activity at 50 \/kg. Finally, toxicological studies determined a LD50 &gt; 2,000 mg\/kg and, after 28 day of treatment with 6\u2010HOF (50 mg\/kg) by intragastric route, mice did not exhibit evidence of any significant toxicity. In conclusion, experiments showed that 6\u2010HOF exerts significant relaxant activity through calcium channel blockade, and possibly, by NO\/cGMP\u2010system stimulation on rat trachea, which interferes with the contraction mechanism of smooth muscle cells in the airways. In addition, the flavonoid shows potential anti\u2010asthmatic properties in an anti\u2010allergic pathway. Furthermore, because the pharmacological and safety evidence, we propose this flavonoid as lead for the development of a novel therapeutic agent for the treatment of asthma and related respiratory diseases.<\/jats:p>","DOI":"10.1002\/ddr.21484","type":"journal-article","created":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T07:54:05Z","timestamp":1541404445000},"page":"218-229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Functional mechanism of tracheal relaxation, antiasthmatic, and toxicological studies of 6\u2010hydroxyflavone"],"prefix":"10.1002","volume":"80","author":[{"given":"Ang\u00e9lica","family":"Flores\u2010Flores","sequence":"first","affiliation":[{"name":"Facultad de Farmacia Universidad Aut\u00f3noma del Estado de Morelos  Cuernavaca Morelos Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1860-0744","authenticated-orcid":false,"given":"Samuel","family":"Estrada\u2010Soto","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia Universidad Aut\u00f3noma del Estado de Morelos  Cuernavaca Morelos Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Mill\u00e1n\u2010Pacheco","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia Universidad Aut\u00f3noma del Estado de Morelos  Cuernavaca Morelos Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Baz\u00e1n\u2010Perkins","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Enfermedades Respiratorias  Ciudad de M\u00e9xico Mexico"},{"name":"Escuela de Medicina y Ciencias de la Salud, Tecnol\u00f3gico de Monterrey  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Villalobos\u2010Molina","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina, FES\u2010Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico  Tlalnepantla Estado de M\u00e9xico Mexico"},{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Moreno\u2010Fierros","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina, FES\u2010Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico  Tlalnepantla Estado de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogelio","family":"Hern\u00e1ndez\u2010Pando","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n  Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6039-7172","authenticated-orcid":false,"given":"Sara","family":"Garc\u00eda\u2010Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia Universidad Aut\u00f3noma del Estado de Morelos  Cuernavaca Morelos Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio C\u00e9sar","family":"Rivera\u2010Leyva","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia Universidad Aut\u00f3noma del Estado de Morelos  Cuernavaca Morelos Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,5]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"29","article-title":"Mechanism of relaxant action of ethyl 6\u2010amino\u20105\u2010cyano\u20102\u2010methyl\u20104\u2010(pyridin\u20104\u2010yl)\u20104H\u2010pyran\u20103\u2010carboxylate mainly through calcium channel blockade in isolated rat trachea","volume":"6","author":"Alem\u00e1n\u2010Pantitl\u00e1n S.","year":"2016","journal-title":"Journal of Applied Pharmaceutical Sciences"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.07.006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.95.08030457"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2015.05.055"},{"key":"e_1_2_9_7_1","unstructured":"ChemAxon. 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