Ferulic acid improves glucose homeostasis by modulation of key diabetogenic activities and restoration of pancreatic architecture in diabetic rats.

There are increasing concerns on the rising cases of diabetes mellitus with type 2 diabetes (T2D) being of major interest as well as the cost of its treatment. Plant phenolic compounds are natural and potent antioxidants that have been widely reported for their antidiabetic activities properties, one of which is ferulic acid. The effect of ferulic acid (FA) on major diabetogenic activities and pancreatic architecture linked to T2D was investigated in T2D rats. T2D was induced in male Sprague-Dawley rats using the fructose-streptozotocin model. Diabetic rats were treated with FA at 150 or 300 mg/kg bodyweight (bw). Normal control consisted of rats administered with food and water, while diabetic control consisted of untreated diabetic rats. Metformin was used as the standard drug. The rats were humanely sacrificed after 5 weeks of treatment. Their blood, liver, and pancreas were collected for analysis. Total glycogen content and carbohydrate metabolic enzymes activities were analyzed in the liver, while the pancreas and serum from blood were analyzed for oxidative stress biomarkers, purinergic and cholinergic enzyme activities, and amylase and lipase activities. The pancreatic tissue was further subjected to microscopic and histological examinations. FA caused a significant (p < 0.05) decrease in blood glucose level, with concomitant increase in serum insulin level. Treatment with FA also led to elevated levels of GSH, HDL-c, SOD, and catalase activities, while concomitantly suppressing malondialdehyde, cholesterol, triglyceride, LDL-c, NO, ALT, AST, creatinine, urea, and uric acid levels, acetylcholinesterase, ATPase, ENTPDase, 5'-nucleotidase, lipase, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-biphosphatase activities. Histology analysis revealed an intact pancreatic morphology in FA-treated diabetic rats. While transmission electron microscopy (TEM) analysis revealed an intact pancreatic ultrastructure and increased number of insulin granules in ß-cells. Taken together, these results portray that the antidiabetic potentials of ferulic acid involves modulation of major diabetogenic activities and maintenance of the pancreatic ultrastructure architecture.

Kolaviron stimulates glucose uptake with concomitant modulation of metabolic activities implicated in neurodegeneration in isolated rat brain, without perturbation of tissue ultrastructural morphology.

Reduced glucose uptake usually occurs in type 2 diabetes due to down-regulation of brain glucose transporters. The potential of kolaviron, a biflavonoid from Garcinia kola to stimulate glucose uptake and suppress glucose-induced oxidative toxicity were investigated in rat brain. Its molecular interactions with the target proteins were investigated in silico. Kolaviron was incubated with excised rat brain in the presence of glucose for 2 h, with metformin serving as a positive control. Kolaviron caused a significant (p < 0.05) increase in glucose uptake, glutathione level, superoxide dismutase, catalase, ATPase, ENTPDase and 5'-nucleotidase activities, while concomitantly depleting malondialdehyde level, acetylcholinesterase and butyrylcholinesterase activities compared to brains incubated with glucose only. Electron microscopy (SEM and TEM) analysis revealed kolaviron had little or no effect on the ultrastructural morphology of brain tissues as evidenced by the intact dendritic and neuronal network, blood vessels, mitochondria, synaptic vesicles, and pre-synaptic membrane. SEM-EDX analysis revealed a restorative effect of glucose-induced alteration in brain elemental concentrations, with total depletion of aluminum and zinc. MTT analysis revealed kolaviron had no cytotoxic effect on HT-22 cells. Molecular docking revealed a potent interaction between kolaviron and catalase at the SER114 and MET350 residues, with a binding energy of 12 kcal/mol. Taken together, these results portray the potential of kolaviron to stimulate glucose uptake while concomitantly coffering a neuroprotective effect.

Hyperglycemia alters lipid metabolism and ultrastructural morphology of cerebellum in brains of diabetic rats: Therapeutic potential of raffia palm (Raphia hookeri G. Mann & H. Wendl) wine.

The present study investigated the effect of raffia palm (Raphia hookeri) wine (RPW) on hyperglycemia-mediated lipid metabolites and pathways, functional chemistry and ultrastructural morphology of cerebellums in type 2 diabetes (T2D). T2D was induced in male Sprague-Dawley rats by feeding with 10% fructose ad libitum for 2 weeks before injecting intraperitoneally with 40 mg/kg bodyweight (bw) streptozotocin. Following confirmation of hyperglycemia at blood glucose >200 mg/dL, diabetic rats were treated with RPW at 150 and 300 mg/kg bw respectively. Metformin served as the standard drug. Negative and normal controls consisted of untreated diabetic and non-diabetic rats, respectively. After 5 weeks of treatment, the rats were humanely sacrificed, and their cerebellum excised from the harvested brains. GC-MS analysis revealed significant alterations in cerebellar lipid metabolites depicted by changes in unsaturated and saturated fatty acids, fatty - esters, alcohols, and amides, glycols and steroids on induction of T2D. Pathway enrichment analysis of the lipid metabolites revealed inactivation of arachidonic metabolic pathway following T2D induction. Treatment with both doses of RPW restored most of the metabolites, while reactivating arachidonic acid metabolism (high dose only). Low dose of RPW led to the activation of retinol metabolism. Both doses of RPW maintained cerebellar functional chemistry as revealed by FTIR analysis. TEM analysis revealed swollen mitochondria, depleted numbers of synaptic vesicles, and shrunk synaptic clefts following induction of T2D. These ultrastructural morphologies were improved in RPW-treated rats. These results portray the therapeutic potential of raffia palm wine in the management of neurodegenerative complications in T2D.