Ex Vivo and In Silico Approaches of Tracheal Relaxation through Calcium Channel Blockade of 6-Aminoflavone and Its Toxicological Studies in Murine Models


Por: Flores-Flores, Angelica, Estrada-Soto, Samuel, Millan-Pacheco, Cesar, Bazan-Perkins, Blanca, Hernandez-Pando, Rogelio, Ibarra-Barajas, Maximiliano, Villalobos-Molina, Rafael

Publicada: 1 jul 2023
Resumen:
Asthma is a condition in which a person's airways become inflamed, narrowed, and produce greater amounts of mucus than normal. It can cause shortness of breath, chest pain, coughing, or wheezing. In some cases, symptoms may be exacerbated. Thus, the current study was designed to determine the mechanism of action of 6-aminoflavone (6-NH2F) in ex vivo experiments, as well as to determine its toxicity in acute and sub-chronic murine models. Tissues were pre-incubated with 6-NH2F, and concentration-response curves to carbachol-induced contraction were constructed. Therefore, tracheal rings pre-treated with glibenclamide, 2-aminopyridine, or isoproterenol were contracted with carbachol (1 & mu;M), then 6-NH2F relaxation curves were obtained. In other sets of experiments, to explore the calcium channel role in the 6-NH2F relaxant action, tissues were contracted with KCl (80 mM), and 6-NH2F was cumulatively added to induce relaxation. On the other hand, tissues were pre-incubated with the test sample, and after that, CaCl2 concentration-response curves were developed. In this context, 6-NH2F induced significant relaxation in ex vivo assays, and the effect showed a non-competitive antagonism pattern. In addition, 6-NH2F significantly relaxed the contraction induced by KCl and CaCl2, suggesting a potential calcium channel blockade, which was corroborated by in silico molecular docking that was used to approximate the mode of interaction with the L-type Ca2+ channel, where 6-NH2F showed lower affinity energy when compared with nifedipine. Finally, toxicological studies revealed that 6-NH2F possesses pharmacological safety, since it did not produce any toxic effect in both acute and sub-acute murine models. In conclusion, 6-aminoflavone exerted significant relaxation through calcium channel blockade, and the compound seems to be safe.

Filiaciones:
Flores-Flores, Angelica:
 Inst Nacl Enfermedades Resp, Dept Inmunofarmacol, Mexico City 14080, Mexico

 Tecnol Monterrey, Escuela Med & Ciencias Salud, Mexico City 14380, Mexico

Estrada-Soto, Samuel:
 Univ Autonoma Estado Morelos, Fac Farm, Cuernavaca 62209, Mexico

Millan-Pacheco, Cesar:
 Univ Autonoma Estado Morelos, Fac Farm, Cuernavaca 62209, Mexico

Bazan-Perkins, Blanca:
 Inst Nacl Enfermedades Resp, Dept Inmunofarmacol, Mexico City 14080, Mexico

 Tecnol Monterrey, Escuela Med & Ciencias Salud, Mexico City 14380, Mexico

Hernandez-Pando, Rogelio:
 Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City 14080, Mexico

Ibarra-Barajas, Maximiliano:
 Univ Nacl Autonoma Mexico, Fac Estudios Super Iztacala, Unidad Biomed, Tlalnepantla 54090, Mexico

Villalobos-Molina, Rafael:
 Univ Nacl Autonoma Mexico, Fac Estudios Super Iztacala, Unidad Biomed, Tlalnepantla 54090, Mexico
ISSN: 22279059
Editorial
MDPI AG, ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, Suiza
Tipo de documento: Article
Volumen: 11 Número: 7
Páginas:
WOS Id: 001037972200001
ID de PubMed: 37509509
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