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J Nat Prod ; 84(4): 1012-1021, 2021 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-33706515

RESUMEN

Natural alkaloids, a large class of plant-derived substances, have attracted considerable interest because of their pharmacological activities. In this study, the in vivo pharmacokinetics and anti-inflammatory profile of anatabine, a naturally occurring alkaloid, were characterized in rodents. Anatabine was found to be bioavailable and brain-penetrant following systemic administration. Following intraperitoneal (i.p.) administration (1, 2, and 5 mg/kg), anatabine caused a dose-dependent reduction in carrageenan-induced paw edema in rats; in mice, it inhibited the production of pro-inflammatory cytokines and simultaneously elevated the levels of an anti-inflammatory cytokine in a dose-dependent manner 2 h after lipopolysaccharide challenge. Furthermore, anatabine (∼10 and ∼20 mg/kg/day for 4 weeks; inhalation exposure) had effects in a murine model of multiple sclerosis, reducing neurological deficits and bodyweight loss. Comparative studies of the pharmacokinetics and anti-inflammatory activity of anatabine demonstrated its bioequivalence in rats following i.p. administration and inhalation exposure. This study not only provides the first detailed profile of anatabine pharmacokinetics in rodents but also comprehensively characterizes the anti-inflammatory activities of anatabine in acute and chronic inflammatory models. These findings provide a basis for further characterizing and optimizing the anti-inflammatory properties of anatabine.


Asunto(s)
Alcaloides/farmacología , Antiinflamatorios/farmacología , Piridinas/farmacología , Alcaloides/farmacocinética , Animales , Antiinflamatorios/farmacocinética , Encéfalo/metabolismo , Carragenina , Citocinas , Edema/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Piridinas/farmacocinética , Ratas , Ratas Wistar
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