Antidiabetic Effects of Thymol and Beta Carophylene Compounds from Ocimum gratissimum Linn Using in silico and in vivo Approaches

Abstract

Ocimum gratissimum (OG) Linn. is known to possess hypoglycemic activities, and its phytochemicals, which include thymol and beta-carophylene (BCP), have also been reported to demonstrate hypoglycemic activity. Therefore, this study investigated the antidiabetic activity of thymol and BCP using in vivo and in silico approaches. Twenty male Wistar rats were divided into four groups (n=5): Control, DIA, DIA+THY, and DIA+BCP for the in vivo study. The control group comprised normal animals; while diabetes mellitus was induced in the DIA, DIA+THY, and DIA+BCP groups by alloxan monohydrate (100 mg/kg, i.p), followed by oral administration of distilled water, thymol (20 mg/kg), and BCP (200 mg/kg) respectively, for 14 days. Fasting blood glucose (FBG), hepatic glucose-6-phosphatase activity, and liver functions were determined. In silico, thymol and BCP were docked with peroxisome proliferator-activated receptor alpha (PPAR- α), peroxisome proliferator- activated receptor gamma (PPAR-γ), insulin receptor (IR), protein tyrosine phosphatase 1B (PTP1β), dipeptidyl peptidase-4 (DPP-4), glycogen synthase kinase-3β (GSK-3β), and aldose reductase (AR) using the AutoDock Vina plugin in PyRx software. Additionally, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile of thymol and BCP were determined. Elevated FBG and hepatic glucose-6-phosphatase activity were observed in the DIA group, and these were significantly reduced by thymol and BCP treatment in the DIA+THY and DIA+BCP groups, respectively. All the targeted proteins docked favourably with either thymol or BCP however, the least binding affinities were observed in AR and DPP-4. Both thymol and BCP had ADMET scores that met the decision rule for toxicity and safety. We concluded that thymol and BCP inhibit glucose-6-phosphatase activities in diabetic rats and may likely modulate aldose reductase and DPP-4 activity to bring about their antidiabetic properties, among other favorable pathways.