Low-Dose 17β-Estradiol Supplemented with Andrographis Paniculata Improved Glucose and Lipid Homeostasis in a Type-2 Diabesity Mice Model

Abstract

Estrogens play an important role in metabolic homeostasis. However, its risk of oncogenecity and cardiovascular adverse effects underscores its therapeutic benefits. This study investigated the metabolic effect of low dose estrogen supplemented with Andrographis paniculata on type-2 diabesity mice model. The experimental animals maintained on high fat diet were induced diabetes with streptozotocin (100 mg/kg) after intraperitoneal injection of 50 mg/kg nicotinamide. Low dose estrogen (0.02 mg/kg) was administered alone as well as in combination with 50, 150 and 500 mg/kg of the ethanol extract of A. paniculata. These doses of the extract, vehicle (5 ml/kg distilled water) and two reference standards pioglitazone (30 mg/kg) and metformine (100 mg/kg) were used as controls. Oral glucose tolerance test was used to determine the effect of treatment on pancreatic β-cell function and insulin sensitivity following oral glucose load of 2 g/kg. Lipid profile tests and blood glucose measurements were used to evaluate effect of treatment on lipid homeostasis and chronic diabetes respectively. Combination of low dose estradiol with 150 and 500 mg/kg of the extract showed significant (p<0.05) reduction in blood glucose when compared to their individual monotherapeutic effects. Co-administration of the extract with estradiol at all doses of the extract produced significant (p<0.05) improvement in oral glucose tolerance as depicted by smaller AUC when compared to either the extract or estradiol alone. Low dose estradiol was unable to significantly improve diabesity associated lipid profile abnormalities. However, combination of both low doses of the extract (50 mg/kg) and estradiol showed significant (p<0.05) reduction in serum triglyceride (TG) and LDL -cholesterol as well as significant (p<0.05) increase in HDL compared to vehicle control group. These findings established that augmentation of low-dose estrogen with A. paniculata resulted in the improvement of glucose and lipid homeostasis in a type-2 diabesity mice model compared to their individual effects.