Antidiabetic property of miracle fruit plant (Synsepalum dulcificum Shumach. & Thonn. Daniell) leaf extracts in fructose-fed streptozotocin-injected rats via anti-inflammatory activity and inhibition of carbohydrate metabolizing enzymes

Ethnopharmacological relevance: Miracle fruit plant (Synsepalum dulcificum) has many applications in folk medicine. The leaves are used traditionally to treat diabetes and other diseases. The antidiabetic potential of Synsepalum dulcificum leaves in rats has been studied but the mechanisms involved are yet to be elucidated. Aim: The present study aimed to provide insight into the antidiabetic mechanisms of methanol and flavonoid-rich leaf extracts of Synsepalum dulcificum (MSD and FSD, respectively). Methods: In vivo effects of administering 30 mg/kg or 60 mg/kg MSD and FSD for 21 consecutive days to rats after type II diabetes was induced through 14 days of fructose feeding and injection of one dose of streptozotocin, were assessed. Glibenclamide (5 mg/kg) served as the reference drug. In addition, in vitro inhibitory activity of MSD and FSD on the carbohydrate metabolizing enzymes, a-amylase and glucokinase, were evaluated, with acarbose as the reference drug. Moreover, in silico analyses to elucidate the contribution of key polyphenolics to the antidiabetic activity of the extracts through docking with glucokinase were performed. Results: MSD and FSD significantly reduced HbA1c and serum levels of interleukin-6 and TNF-alpha (p < 0.05) in diabetic animals. Conversely, serum level of insulin and hepatic hexokinase activity were increased (p < 0.05) in extract treated groups. Both extracts showed alpha-amylase and alpha-glucosidase inhibitory activities. Quercetin, caffeic acid and chlorogenic acid in extracts showed strong binding affinities with glucokinase in the molecular docking analyses. Conclusion: Results from this study indicate that increased insulin synthesis, reduction of inflammation and inhibition of carbohydrate metabolizing enzymes are likely mechanisms by which MSD and FSD exert anti diabetic action in type II diabetic rats.