Thesis Abstract

Type 2 diabetes (T2D) occurs when there is an advanced determent in insulin action (insulin resistance, IR), which proceeds toβ-cell dysfunction. This present study assessed the modulatory effects of Buchholziacoriacea(B. coriacea) seeds extract in high fructose-fed, streptozotocin-induced T2D in male Wistar rats.

Methanolic extract (MEBC), hexane fraction (HFBC), ethyl acetate fraction (EFBC) and n-butanol fraction of BC (BFBC) were prepared using 70% methanol and successive solvent partitioning method respectively. Antioxidant activities of 1-1-diphenyl 2-picryl hydrazyl (DPPH), nitric oxide radical scavenging assay (NOSA) and hydroxyl radical scavenging activities (HRSA) were assessed as well as α-amylase inhibition in vitro. High fructose (20%, p.o) (2 weeks) followed by streptozotocin (STZ) (40 mg/kg, i.p.) (FRU + STZ) (day 14) administered to achieve T2D in vivo. Control normal and diabetic untreated (FRU + STZ) rats were administered carboxymethyl cellulose (CMC) (1 ml/kg, p.o). Diabetic treated rats received BFBC (20, 200, 400 mg/kg, p.o), metformin (7.14 mg/kg, p.o) and glibenclamide (0.07 mg/kg, p.o) respectively.

BFBC had the highest percentage yield, DPPH and α-amylase inhibition activities, although, EFBC had a better inhibitory activities on HRSA and NOSA respectively. Also, untreated diabetic rats showed increase (p< 0.05 – 0.001) in blood glucose levels (BGLs), insulin (6 folds) and lipid peroxidation (LPO) levels in pancreas when compared with normal group. BFBC (20, 200, 400 mg/kg) showed decrease (p< 0.05) in BGLs in a time dependent manner in the BFBC treated animals. Similarly, BFBC produced a dose dependent decrease in serum insulin levels by 51% (20 mg/kg), 54% (200 mg/kg) and 70% (400 mg/kg) respectively. These effects were also comparable to metformin and glibenclamide. BFBC treatments elevated (p> 0.05) high density lipoprotein, but decreased (p> 0.05) triglycerides, total cholesterol and low density lipoprotein levels compared with control group while it lowers plasma alkaline phosphatase activities and urea (p< 0.05) compared with untreated group. BFBC (400 mg/kg) elevated total protein levels in the pancreas and heart by 103% and 7% compared with the untreated rats. Treatment of diabetic rats with BFBC elevated the body weights by 21% (20 and 200 mg/kg) and 36% (400 mg/kg) respectively. BFBC when administered did not significantly alter hematological, electrolytes and antioxidant enzyme activities in all rats. Histological assessments showed that sections of the pancreas, liver, kidney and heart from BFBC treated animals had reduced tissue damage compared with the untreated groups. Fourteen (14) bioactive compounds highest in oleic, stearic, 2-methyl-pyrrolidine-2-carboxylic, n-hexadecanoic, and 13-docosenoic acids were present in BFBC given Gas-Chromatography/Mass-Spectrometry analysis.

Thediabetic animal model was able to present the natural history of the disease in human T2D. Also, BFBC doses used in this study demonstrate potentials against in vitro and in vivo oxidative stress, hyperinsulinaemia, dyslipidemia as well as declension in β-cell function in T2D rat experiment. Further, application of some derivatives of BFBC in the treatment of problems associated with T2Dmay be useful.

Keywords Buchholziacoriacea, Streptozotocin, Fructose, Type 2 Diabetes, Metformin, Glibenclamide.

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