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
gold, Gold
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