NEUROPHARMACOLOGICAL EVALUATION OF FEVER TREE (Eucalyptus globulus Labill) IN FRUCTOSE/STREPTOZOTOCIN-INDUCED DIABETIC RATS

Abstract

Diabetic encephalopathies are a major problem worldwide. This research evaluated the antioxidant, anti-diabetic and neuro-pharmacological effect of ethanol extract of Eucalyptus globulus Labil leaf in fructose-streptozotocin-induced diabetic rats. Ethanol leaf extract of Eucalyptus globulus was screened for phytochemical constituents, subjected to HPLC analysis and assessed for in vitro antioxidant and anti-diabetic properties. For the in vivo experiment, type – 2 diabetes was induced by feeding rats with 10% fructose in drinking water for 14 days and administering a single intraperitoneal injection of 40 mg/kg streptozotocin (STZ). Confirmed diabetic animals (fasting blood glucose ≥ 200 mg/dL) were orally treated with varying doses (100-400 mg/kg) of the extract for 21 days with glibenclamide as the reference drug. Blood and brain tissues were processed for biochemical analyses, gene expression analyses, and histopathological evaluation at the end of the period of treatment. The flavonoids (catechin, quercetin and apigenin) and other compounds (pinitol and robinetinidol) were identified in the extract by HPLC-DAD analysis. The extract showed appreciable inhibitory activities against the carbohydrate metabolizing enzymes, α-amylase and α-glucosidase as shown by their IC50 values. At 200 μg/mL, the α-amylase inhibitory activity of the extract and acarbose were 84.00±1.17% and 85.91±0.27%, respectively. The extract displayed better α-glucosidase inhibitory activity than acarbose. At 200 μg/ml, the α-glucosidase inhibitory activity of the extract and acarbose were 96.13±1.00% and 85.50±1.44% respectively. The results of the in vivo study revealed that the untreated diabetic group with increased blood glucose level showed decreased expression of BDNF and GRIN1 but increased expression of IL-6. This was accompanied by increased concentrations of malondialdehyde, and increased activity of myeloperoxidase, acetylcholinesterase, monoamine oxidase but decreased dopamine level, tyrosine hydroxylase activity, and glutamate dehydrogenase activity along with histopathological aberrations in brain tissue. Administration of the Eucalyptus globulus leaf extract significantly (p<0.05) increased the expression of BDNF and GRIN1 while decreasing IL-6 expression. The extract also ameliorated the observed hyperglycemia, redox imbalance, other neurochemical disturbances, and histopathological aberrations. The increased acetylcholinesterase activity in the diabetic control group was decreased in the extract-treated group by 75.57% while decreased tyrosine hydroxylase activity and dopamine level in the diabetic control group were increased by 73.7% and 67.7%, respectively in the extract-treated group. These results show that Eucalyptus globulus leaves protect against diabetic brain dysfunction through enhanced expression of BDNF and GRIN1 and reduced expression of IL-6 genes and may be a potential therapeutic agent for the management of diabetic cerebrovascular problems and other related complications.