Glibenclamide-pregnenolone derivative has greater hypoglycemic effects and biodistribution than glibenclamide-OH in alloxan-rats

Abstract

Aim. The present study was designed to investigate the activity of two glibenclamide derivatives on glucose concentration. An additional aim was to identify the biodistribution of glibenclamide derivatives in different organs in a diabetic animal model. Methods. The effects of two glibenclamide derivatives on glucose concentration were evaluated in a diabetic animal model. In addition, glibenclamide derivatives were bound to Tc-99m using radioimmunoassay methods. To evaluate the pharmacokinetics of the glibenclamide derivatives over time (15, 30, 45 and 60 min) the Tc-99m-glibenclamide conjugates were used. Results. The results showed that glibenclamide-pregnenolone had greater hypoglycemic activity than glibenclamide or glibenclamide-OH. The data also showed that the biodistribution of Tc-99m-glibenclamide-OH in all organs was less than that of the Tc-99m-glibenclamide-pregnenolone derivative. Conclusions. The glibenclamide-pregnenolone derivative had greater hypoglycemic effects and its biodistribution was wider than glibenclamide-OH. The data suggest that the steroid nucleus may be important to the hypoglycemic activity of the glibenclamide-pregnenolone derivative and this could be related to the degree of lipophilicity induced by the steroid nucleus in the chemical structure of glibenclamide-pregnenolone.

The effect of progesterone and pregnenolone on diabetes status in Chinese rural population: a dose–response analysis from Henan Rural Cohort

“…Thus, a study conducted in the general population is needed to evaluate the effect of progestogen on T2DM. Additionally, an experimental research with rats reported that the effect of a high dose of glibenclamidepregnenolone on anti-hyperglycemic activity was better than glibenclamide or glibenclamide-OH, which was in consistence with the present study to some degree (38). The results of gender stratification analysis were similar to the findings in all participants, which partly may be due to the similar source of progestogen production (adrenal) in postmenopausal women and men (39,40).…”

Alpha-glucosidase inhibitory and antiplasmodial properties of terpenoids from the leaves ofBuddleja salignaWilld

“…In a different anti-diabetic assay model, betulinic acid was found to increase glucose uptake and enhanced glycogen synthesis 14 . It is proposed that a steroid nucleus is important for a high hypoglycemic effect and possibly conditioning the high degree of lipophilicity 15 and they exhibit anti-diabetic properties with relatively low toxicity 16,17 . According to Li et al 18 , the mechanism of action of terpenoids and steroids in in-vivo studies might occur through stimulation of pancreatic islets leading to an increase in insulininduced glucose uptake.…”

Biochemical Efficacy of <i>Nigella Sativa Oil</i> and Metformin on Induced Diabetic Male Rats

“…Group II: n= 10, control Diabetic rats, received daily dose of distilled water. Group III: n= 10, diabetic rats treated with metformin at a dose 350 mg/kg bw/day (Figueroa-Valverde et al, 2012). Group IV: n= 10, diabetic rats treated with metformin at a dose 350 mg/kg bw/day (Figueroa-Valverde et al, 2012) and Nigella sativa oil at a dose 1 mL/kg bw/day (Zaoui et al, 2002).…”

“…Group III: n= 10, diabetic rats treated with metformin at a dose 350 mg/kg bw/day (Figueroa-Valverde et al, 2012). Group IV: n= 10, diabetic rats treated with metformin at a dose 350 mg/kg bw/day (Figueroa-Valverde et al, 2012) and Nigella sativa oil at a dose 1 mL/kg bw/day (Zaoui et al, 2002). Group V: n= 10, diabetic rats treated with Nigella sativa oil at a dose 1 mL/kg bw/day (Zaoui et al, 2002).…”