Dacryodes edulis (G. Don) H.J. Lam modulates glucose metabolism, cholinergic activities and Nrf2 expression, while suppressing oxidative stress and dyslipidemia in diabetic rats

Abstract

Ethnopharmacological relevanceDacryodes edulis L. is an evergreen tree indigenous to western and eastern Africa which is utilized for nutritional and medicinal purposes. Folklorically, different parts of the tree are used in treating and managing diabetes and its complications. AimsThe antidiabetic effect of the butanol fraction of D. edulis ethanol extract (BFDE) was studied in fructose-streptozotocin induced type 2 diabetic rats. MethodsThe ethanol extract was fractionated to yield the hexane, dichloromethane, ethyl acetate, butanol and aqueous fractions. The in vitro antidiabetic activities of the fractions were determined by their ability to inhibit α-glucosidase activity. BDFE was the most active and showed no cytotoxic effect while stimulating glucose uptake in 3T3-L1 adipocytes. Thus, selected for in vivo study. Diabetic rats were grouped into 4. The negative control group was administered water only, another group was treated with metformin (200 mg/kg bodyweight), while the other groups were administered BDFE at 150 and 300 mg/kg bodyweight respectively. Two other groups consisting of normal rats were given water and BFDE (300 mg/kg bodyweight) respectively, with the former serving as normal control. After 6 weeks of intervention, the rats were humanely sacrificed using appropriate anaesthesia. ResultsTreatment with the fraction significantly (p < 0.05) reduced the blood glucose level of the diabetic rats, with concomitant increase in serum insulin secretion. It also caused significant (p < 0.05) elevation of reduced glutathione level, superoxide dismutase, catalase, α-amylase, and ATPase activities, with concomitant depletion in myeloperoxidase activity, NO and MDA levels of the serum and pancreas. The pancreatic morphology and β-cell function were significantly improved in BFDE-treated rats, with restoration of the pancreatic capillary networks. Treatment with BFDE significantly (p < 0.05) inhibited the activities of glycogen phosphorylase, fructose 1,6 biphosphatase, glucose 6 phosphatase, and acetylcholinesterase, while suppressing the expression of Nrf2. HPLC analysis revealed the presence of gallic acid, vanillic acid, vanillin, and (−)-epicatechin in the fraction. ConclusionThese results portray the antidiabetic and antioxidative properties of BFDE, which may be a synergistic consequence of the identified phenolics.