Attenuation of PI3K/AKT signaling pathway by Ocimum gratissimum leaf flavonoid-rich extracts in streptozotocin-induced diabetic male rats

Abstract

Diabetes is a group of medical conditions characterized by the body's inability to effectively control blood glucose levels, due to either insufficient insulin synthesis in type 1 diabetes or inadequate insulin sensitivity in type 2 diabetes. According to this research, the PI3K/AKT pathway of Ocimum gratissimum leaf flavonoid-rich extracts in streptozotocin-induced diabetic rats was studied. We purchased and used a total of forty (40) male Wistar rats for the study. We divided the animals into five (5) different groups: normal control (Group A), diabetic control (Group B), low dose (150 mg/kg body weight) of Ocimum gratissimum flavonoid-rich leaf extract (LDOGFL) (Group C), high dose (300 mg/kg body weight) of Ocimum gratissimum flavonoid-rich leaf extract (HDOGFL) (Group D), and 200 mg/kg of metformin (MET) (Group E). Streptozotocin induced all groups except Group A, which serves as the normal control group. The experiment lasted for 21 days, following which we sacrificed the animals and harvested their brains for biochemical analysis on the 22nd day. We carried out an analysis that included reduced glutathione (GSH), glutathione transferases (GST), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), along with GLUT4, MDA, pro-inflammatory cytokines, NO, neurotransmitters, cholinergic enzyme activities, cardiolipin, and the gene expression of PI3K/AKT. The obtained result indicates that the flavonoid-rich extracts of O. gratissimum significantly enhanced the levels of GSH, GST, CAT, GPx, and SOD, as well as GLUT4 and cardiolipin. The levels of GSH, GST, CAT, GPx, and SOD, as well as GLUT4 and cardiolipin, were significantly increased by gratissimum. Moreover, the extracts decrease the levels of MDA, pro-inflammatory cytokines, NO, neurotransmitters, and cholinergic enzyme activities. Additionally, the flavonoid-rich extracts of O. gratissimum significantly improved the AKT and PI3K gene expressions in diabetic rats. gratissimum had their AKT and PI3K gene expressions significantly (p < 0.05) improved. The findings indicate that O. gratissimum leaf flavonoids have the potential to treat diabetes mellitus. gratissimum leaf flavonoids possess therapeutic potential in themselves and can be applied in the management of diabetes mellitus. Although further analysis can be carried out in terms of isolating, profiling, or purifying the active compounds present in the plant's extract.