ABSTRACT
Diabetes mellitus is an aberration in sugar metabolism that exhibits high blood glucose as its key indicator due to faulty insulin recognition or secretion. Approximately 463 million persons are currently plagued by the disease worldwide. Its widespread prevalence, coupled with the challenges of palliative oral hypoglycaemic drugs, has instigated investigations into the acclaimed antidiabetic properties of some plants. Consequently, this study investigated the antidiabetic efficacy of Terminalia macroptera stem bark via aqueous extract, AE (200 mg/kg/day), ethanol extract, EE (200 mg/kg/day) and alkaloid-rich extract, ARE (100 mg/kg/day) in Wistar albino rats.
The AE and EE were obtained by maceration in distilled water and absolute ethanol, respectively, in line with the decoction techniques used by locals, while ARE were extracted and purified by chromatographic techniques. Alkaloid-rich extract was further characterized via the fourier transform infrared and gas chromatography-mass spectroscopy. In vitro evaluation of the extracts for reducing power and anti-inflammatory properties were done using standard spectrophotometric methods, while in vivo study entailed the investigation of extract-treated diabetic rats and controls rats (n = 5). Diabetic rats were induced intraperitoneally with 55 mg/kg body weight streptozotocin and treated orally for 70 days. At the end of the experiment, the effects of the extracts were examined and compared with glibenclamide (10 mg/kg/day). Serum was assayed for the concentrations of glucose, lipids, insulin, C-peptide, testosterone and -amylase activities. Liver homogenates were evaluated for glycogen and antioxidants’ activities while -cell mRNA expressions of pancreatic duodenal homeobox-1, insulin-1, tumor necrosis factor- and interleukin-1 were examined and compared with -actin reference genes.
Alkaloid-rich extract characterization exposed high amount of non-protein cyclic amides like 7,9–diethyl-2,4-bis(dimethylamine)-10-imino-8-thio-1,7,9-triazaspiro[4.5]-1,3-decadiene-6,8-dione and furazano [3,4-b]-6-(1-pyrrolidinyl)-pyrazin-5(4H)-one. The phytochemical analysis showed that the extracts compared well with ascorbic acid and reflected reducing power in the order of EE > AE > ascorbic acid > ARE, while their anti-inflammatory properties compared with diclofenac and were in the order of diclofenac > AE > EE > ARE, with the respective IC50 of 130.83 20.19 g/ml, 137.72 12.72 g/ml, 361.36 71.69 g/ml and 704.81 66.84
xxi
g/ml. In vivo analysis showed that AE caused 55.66% decrease in elevated blood glucose (p < 0.05), although less than those of EE and ARE which instigated 78.95% and 75.15% (p < 0.05), respectively. Upon comparison with glibenclamide, EE and ARE showed better glucose evacuation in the diabetic rats. Interestingly, EE-treated rats alone had glycogen concentrations lowered to normal control levels (p > 0.05). Except for glibenclamide, all the extracts caused reduction in lipid profiles (p < 0.05) but significantly enhanced antioxidant properties (p < 0.05 vs DC). Ethanol extract treatment uniquely stimulated insulin secretion that were significantly higher than those of diabetic control, DC (p < 0.05). This observation was accompanied by C-peptide and testosterone concentrations that were slightly increased, though insignificant. Similarly, EE alone notably enhanced -amylase activity (p < 0.05). PDX-1 gene expressions were downregulated by all extracts, but only ARE was able to down-regulate all target gene expressions to near normal levels (p < 0.05 vs DC). Although EE caused insulin secretion, it however, had up-regulated insulin gene expressions that remained unabated (p > 0.05 vs DC). Inflammatory factor genes were downregulated by all extracts (p < 0.05 vs DC) except glibenclamide. The findings revealed that TMSB possesses antidiabetic properties which were better expressed in EE and ARE. The efficacy of EE treatment was primarily based on glucose mediation caused by insulin secretion from -cells that regained functionality while ARE regulatory effects were dependent on direct mediation of the glucose molecules into tissues, an action most likely due to the extracts interaction at the molecular level via the mechanisms of its cyclic amide contents.
