Ferulic acid mitigates diabetic cardiomyopathy via modulation of metabolic abnormalities in cardiac tissues of diabetic rats.

Cardiovascular abnormalities have been reported as a major contributor of diabetic mortality. The protective effect of ferulic acid on diabetic cardiomyopathy in fructose-streptozotocin induced type 2 diabetes (T2D) rat model was elucidated in this study. Type 2 diabetic rats were treated by oral administration of low (150 mg/kg b.w) and high (300 mg/kg b.w) doses of ferulic acid. Metformin was used as the antidiabetic drug. Rats were humanely euthanized after 5 weeks of treatment, and their blood and hearts were collected. Induction of T2D depleted the levels of reduced glutathione, glycogen, and HDL-cholesterol and the activities of superoxide dismutase, catalase, ENTPDase, and 5'nucleotidase. It simultaneously triggered increase in the levels of malondialdehyde, total cholesterol, triglyceride, LDL-cholesterol, creatinine kinase-MB as well as activities of acetylcholinesterase, angiotensin converting enzyme (ACE), ATPase, glucose-6-phopsphatase, fructose-1,6-bisphophatase, glycogen phosphorylase, and lipase. T2D induction further revealed an obvious degeneration of cardiac muscle morphology. However, treatment with ferulic acid markedly reversed the levels and activities of these biomarkers with concomitant improvement in myocardium structural morphology, which had favorable comparison with the standard drug, metformin. Additionally, T2D induction led to the depletion of 40%, 75%, and 33% of fatty acids, fatty esters, and steroids, respectively, with concomitant generation of eicosenoic acid, gamolenic acid, and vitamin E. Ferulic acid treatment restored eicosanoic acid, 2-hydroxyethyl ester, with concomitant generation of 6-octadecenoic acid, (Z)-, cis-11-eicosenoic acid, tridecanedioic acid, octadecanoic acid, 2-hydroxyethyl ester, ethyl 3-hydroxytridecanoate, dipalmitin, cholesterol isocaproate, cholest-5-ene, 3-(1-oxobuthoxy)-, cholesta-3,5-diene. These results suggest the cardioprotective potential of ferulic acid against diabetic cardiomyopathy.

The antioxidant and antidiabetic potentials of polyphenolic-rich extracts of Cyperus rotundus (Linn.).

In this study, the rhizome of Cyperus rotundus L was investigated for its antioxidant and antidiabetic effects using in vitro and in silico experimental models. Its crude extracts (ethyl acetate, ethanol and aqueous) were screened in vitro for their antioxidant activity using ferric-reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH), as well as their inhibitory effect on α-glucosidase enzyme. Subsequently, the extracts were subjected to Gas Chromatography-Mass Spectrometry (GC-MS) analysis to elucidate their possible bioactive compounds. Furthermore, computational molecular docking of selected phenolic compounds was conducted to determine their mode of α-glucosidase inhibitory activity. The aqueous extract displayed the highest level of total phenolic content and significantly higher scavenging activity in both FRAP and DPPH assays compared to ethyl acetate and ethanol extracts. In FRAP and DPPH assays, IC50 values of aqueous extract were 448.626 µg/mL and 418.74 µg/mL, respectively. Aqueous extract further presented higher α-glucosidase inhibitory activity with an IC50 value of 383.75 µg/mL. GC-MS analysis revealed the presence of the following phenolic compounds: 4-methyl-2-(2,4,4-trimethylpentan-2-yl) phenol, Phenol,2-methyl-4-(1,1,3,3-tetramethylbutyl)- and 1-ethoxy-2-isopropylbenzene. Molecular docking study revealed 1-ethoxy-2-isopropylbenzene formed two hydrogen bonds with the interacting residues in the active site of α-glucosidase enzyme. Furthermore, 4-methyl-2-(2,4,4-trimethylpentan-2-yl) phenol had the lowest binding energy inferring the best affinity for α-glucosidase active site. These results suggest the possible antioxidant and antidiabetic potential of Cyperus rotundus.Communicated by Ramaswamy H. Sarma.

Vanillin improves glucose homeostasis and modulates metabolic activities linked to type 2 diabetes in fructose-streptozotocin induced diabetic rats.

OBJECTIVE: This study investigated the antidiabetic effect of vanillin using in vitro, in silico, and in vivo experimental models. METHODOLOGY: Type 2 diabetes (T2D) was induced in male Sprague-Dawley (SD) rats using fructose-streptozotocin (STZ) , then orally administered low (150 mg/kg bodyweight) or high (300 mg/kg bodyweight) dose of vanillin for 5 weeks intervention period. RESULTS: Vanillin suppressed the levels of blood glucose, serum cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-c), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea, uric acid, when elevated serum insulin, HDL-cholesterol, and concomitantly improved pancreatic ß-cell function, glucose tolerance, and pancreatic morphology. It also elevated both serum and pancreatic tissue GSH level, SOD and catalase activities, and hepatic glycogen level, while depleting malondialdehyde level, α-amylase, lipase, acetylcholinesterase, ATPase, ENTPDase and 5'-nucleotidase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glycogen phosphorylase activities. CONCLUSIONS: The results indicate the potent antidiabetic effect of vanillin against T2D and its associated complications.

Vanillin modulates activities linked to dysmetabolism in psoas muscle of diabetic rats.

Skeletal muscles are important in glucose metabolism and are affected in type 2 diabetes (T2D) and its complications. This study investigated the effect of vanillin on redox imbalance, cholinergic and purinergic dysfunction, and glucose-lipid dysmetabolism in muscles of rats with T2D. Male albino rats (Sprague-Dawley strain) were fed 10% fructose ad libitum for 2 weeks before intraperitoneally injecting them with 40 mg/kg streptozotocin to induce T2D. Low (150 mg/kg bodyweight (BW)) and high (300 mg/kg BW) doses of vanillin were orally administered to diabetic rats. Untreated diabetic rats and normal rats made up the diabetic control (DC) and normal control (NC) groups, respectively. The standard antidiabetic drug was metformin. The rats were humanely put to sleep after 5 weeks of treatment and their psoas muscles were harvested. There was suppression in the levels of glutathione, activities of SOD, catalase, ENTPDase, 5'Nucleotidase and glycogen levels on T2D induction. This was accompanied by concomitantly elevated levels of malondialdehyde, serum creatine kinase-MB, nitric oxide, acetylcholinesterase, ATPase, amylase, lipase, glucose-6-phosphatase (G6Pase), fructose-1,6-biphophastase (FBPase) and glycogen phosphorylase activities. T2D induction further resulted in the inactivation of fatty acid biosynthesis, glycerolipid metabolism, fatty acid elongation in mitochondria and fatty acid metabolism pathways. There were close to normal and significant reversals in these activities and levels, with concomitant reactivation of the deactivated pathways following treatment with vanillin, which compared favorably with the standard drug (metformin). Vanillin also significantly increased muscle glucose uptake ex vivo. The results suggest the therapeutic effect of vanillin against muscle dysmetabolism in T2D as portrayed by its ability to mitigate redox imbalance, inflammation, cholinergic and purinergic dysfunctions, while modulating glucose-lipid metabolic switch and maintaining muscle histology.

Cola nitida infusion modulates cardiometabolic activities linked to cardiomyopathy in diabetic rats.

This study investigated the therapeutic mechanism of Cola nitida seeds on diabetic cardiomyopathy in hearts of diabetic rats. Type 2 diabetic (T2D) rats were treated with C. nitida infusion at 150 or 300 mg/kg body weight (bw). The rats were sacrificed after 6 weeks of treatment, and their hearts harvested. There was an upsurge in oxidative stress on induction of T2D as depicted by the depleted levels of glutathione, superoxide dismutase and catalase activities, and elevated malondialdehyde level. The activities of acetylcholinesterase, and ATPase were significantly elevated, with suppressed ENTPDase and 5'nucleotodase activities in hearts of T2D rats depicting cholinergic and purinergic dysfunctions. Induction of T2D further led to elevated activity of ACE and altered myocardial morphology. Treatment with C. nitida infusion led to reversal of these biomarkers' activities and levels, while maintaining an intact morphology. The infusion caused decreased lipase activity and depletion of diabetes-generated cardiac lipid metabolites, while concomitantly generating saturated and unsaturated fatty acids, fatty esters and alcohols. There was also an inactivation of plasmalogen synthesis and mitochondrial beta-oxidation of long chain saturated fatty acids pathways in T2D rats treated with C. nitida infusion. These results indicate the therapeutic effect of C. nitida infusion against diabetic cardiomyopathy.

Suitability of sugar alcohols as antidiabetic supplements: A review.

The major goals in the management of diabetes are to maintain optimum control of high blood glucose level or hyperglycemia. Dietary modification is one of the most recommended treatment modalities for diabetic patients. The use of foods sweetened with sugar alcohols (also known as polyols) such as xylitol, sorbitol, mannitol, maltitol, lactitol, isomalt and erythritol has brought an escalating interest in the recent years since some sugar alcohols do not rise plasma glucose, as they are partially digested and metabolised. Diet composition and adequacy may be altered by replacing carbohydrates with sugar alcohols. It has been established that these polyols are appropriate sugar substitutes for a healthy lifestyle and diabetic foods. The present review focuses on the evidence supporting the use of sugar alcohols in the management of diabetes, by evaluating their physical and chemical properties, metabolism, absorption, glycemic and insulinemic responses. Although documentation on the glycaemic and insulinemic response of polyols is evident that these compounds have beneficial effects on the better management of hyperglycemia, the possible side effects associated with their normal or higher dosages warned their use according to the relevant Food & Drug Administration guidelines. For the same reason, future studies should also focus on the possible toxicity and side effects associated with the consumption of sugar alcohols in order to define their safety.

Iso-Mukaadial Acetate from Warburgia salutaris Enhances Glucose Uptake in the L6 Rat Myoblast Cell Line.

Diabetes mellitus (DM) is a chronic metabolic disorder which has become a major risk to the health of humankind, as its global prevalence is increasing rapidly. Currently available treatment options in modern medicine have several adverse effects. Thus, there is an urgent need to develop alternative cost-effective, safe, and active treatments for diabetes. In this regard, medicinal plants provide the best option for new therapeutic remedies desired to be effective and safe. Recently, we focused our attention on drimane sesquiterpenes as potential sources of antimalarial and antidiabetic agents. In this study, iso-mukaadial acetate (Iso) (1), a drimane-type sesquiterpenoid from the ground stem bark of Warburgia salutaris, was investigated for glucose uptake enhancement in the L6 rat myoblast cell line. In vitro assays with L6 skeletal muscle cells were used to test for cytotoxicity, glucose utilisation, and western blot analysis. Additionally, the inhibition of carbohydrate digestive enzymes and 1,1-diphenyl-2- picrylhydrazyl (DPPH) scavenging activity were analysed in vitro. The cell viability effect of iso-mukaadial acetate was the highest at 3 µg/mL with a percentage of 98.4. Iso-mukaadial acetate also significantly and dose-dependently increased glucose utilisation up to 215.18% (12.5 µg/mL). The increase in glucose utilisation was accompanied by enhanced 5' adenosine monophosphate-activated protein kinase (AMPK)and protein kinase B (AKT) in dose-dependent manner. Furthermore, iso-mukaadial acetate dose-dependently inhibited the enzymes α-amylase and α-glucosidase. Scavenging activity against DPPH was displayed by iso-mukaadial acetate in a concentration-dependent manner. The findings indicate the apparent therapeutic efficacy of iso-mukaadial acetate isolated from W. salutaris as a potential new antidiabetic agent.