In South Africa, the number of people suffering from diabetes is believed to be rising steadily and the current antidiabetic therapies are frequently reported to have adverse side effects. Ethnomedicinal plant use has shown promise for the development of cheaper, cost-effective antidiabetic agents with fewer side effects. The aim of this study was to investigate the antidiabetic activity and mechanism of action of aqueous leaf extract prepared from Brachylaena elliptica. The potential of the extract for cytotoxicity was evaluated using MTT assay in HepG2 cells. The effects of the plant extract on glucose utilization in HepG2 cells and L6 myotubes, triglyceride accumulation in 3T3-L1, INS-1 proliferation, glucose metabolism in INS-1 cells, and NO production in RAW macrophages were also investigated using cell culture procedures. The inhibitory effects of the extract on the activities of different enzymes including alpha-amylase, alpha-glucosidase, pancreatic lipase, dipeptidyl peptidase IV (DPP-IV), collagenase, and CYP3A4 enzymes were evaluated. 'I he extract also tested against protein glycation using standard published procedure. 'I he plant extract displayed low level of toxicity, where both concentrations tested did not induce 50% cell death. The extract caused a significant increase in glucose uptake in HepG2 liver cells, with efficacy significantly higher than the positive control, berberine. The crude extract also displayed no significant effect on muscle glucose uptake, triglyceride accumulation in 3T3-L1, glucose metabolism in INS-1 cells, alpha-amylase, alpha-glucosidase, DPP-IV, lipase, protein glycation, and collagenase compared to the respective positive controls. The extract displayed a proliferative effect on INS-1 cells at 25 mu g/ml when compared to the negative control. The plant also produced a concentration-dependent reduction in NO production in RAW macrophages and also demonstrated weak significant inhibition on CYP3A4 activity. The findings provide evidence that B. elliptica possess antidiabetic activity and appear to exact its hypoglycemic effect independent of insulin.
