ABSTRACT
Cucurbita ficifolia Bouché fruit containing D-chiro-inositol and Ibervillea sonorae Greene root containing cucurbitane-type glycosides are used to control diabetes in Mexico. Although the hypoglycemic effect of both plants has been demonstrated and some active compounds proposed, their mechanisms are still unknown. The aim of this study was to determine if the incubation with both aqueous extracts avoids the inhibition of contraction induced by phenylephrine similarly to glibenclamide in rat aortic rings. The hypoglycemic aqueous extracts of C. ficifolia and I. sonorae were characterized for their content of either D-chiro inositol or cucurbitanes respectively, and then we assayed the characterized extracts in vitro on the diazoxide-induced relaxation of rat aortic rings precontracted with phenylephrine, using as positive control glibenclamide. I. sonorae extract blocked the KATP channels in a concentration-dependent manner (p < 0.05), whereas C. ficifolia extract had no effect on these channels. I. sonorae extract produces a hypoglycemic effect through a similar mechanism to sulphonylureas in this experimental model; however, hypoglycemic action of C. ficifolia extract should be explained by an independent KATP channels mechanism.
Los frutos de Cucurbita ficifolia conteniendo D-quiro-inositol y las raíces de Ibervillea sonorae conteniendo glucósidos tipo cucurbitano son empleados en el control de la diabetes en México. Aunque el efecto hipoglucémico de ambas plantas ha sido demostrado y se han propuesto algunos de sus compuestos activos, aún se desconoce su mecanismo de acción. El objetivo de este estudio fue determinar si la incubación con ambos extractos acuosos evita la inhibición de la contracción inducida por fenilefrina de manera similar a la glibenclamida en anillos aórticos de rata. Los extractos acuosos hipoglucémicos de C. ficifolia e I. sonorae fueron caracterizados en su contenido de D-quiro inositol o cucurbitanos, respectivamente y entonces fueron estudiados en un modelo in vitro en la relajación inducida por diazóxido en anillos aórticos previamente contraídos con fenilefrina, usando como control positivo glibenclamida. El extracto de Ibervillea sonorae bloqueó los canales KATP de manera dosis-dependiente (p < 0.05), mientras que Cucurbita ficifolia no tuvo efecto en esos canales. El extracto de I. sonorae produce efecto hipoglucémico a través de un mecanismo similar al de las sulfonilureas en este modelo experimental; por su parte, la acción hipoglucemiante del extracto de C. ficifolia debe ser explicado mediante un mecanismo independiente de los canales KATP.
Subject(s)
Animals , Rats , Cucurbitaceae/chemistry , Plant Extracts/pharmacology , Blood Glucose , Hypoglycemic Agents/pharmacology , Aorta , Chromatography, High Pressure Liquid , Diabetes Mellitus, Experimental , KATP Channels , Rats, Wistar , Plant RootsABSTRACT
The estrogen-like effects of norethisterone (NET) seem to be mediated by the interaction of 3ß5alpha- and 3alpha-5alpha-tetrahydronorethisterone (3ß5alpha- and 3alpha5alpha-NET, respectively) with the estrogen receptor. Considering that the in vitro uterine contractile response to sertonin (5-HT) is specifically dependent on estrogen, the aim of the present study was to investigate whether NET and its A-ring reduced metabolites administered in vivo to ovariectomized rats induce uterine sentivity to 5-HT in vitro. The administration of 3ßNET in vivo, wich is the NET metabolite with the highes affinity for the estrogen receptor, induced a maximal contractile response to serotonin similar to that of 17ß-estradiol treatment. The other metabolites induced less uterine activity. According to the effective dose 50, the order of estrogenic potency was 17ß-estradiol>3ß5alphaNET>3alpha5alphaNET>NET>5alphaNET. The estrogenic effect of 3ß5alpha- and 3alpha5alphaNET may be exerted throug their interaction with the estrogen receptor, whereas NET and 5alphaNET, which do not bind to the estrogen receptor and display a minor estrogenic activity, require prior bioconversion to 3ß5alpha NET. The A-ring reduced metabolites of NET, mainly the 3ß5alphaNET, may be exerting estrogenic responses and modulation uterine activity when administered in vivo