Exploring the inhibitory action of betulinic acid on key digestive enzymes linked to diabetes via in vitro and computational models: approaches to anti-diabetic mechanisms.

Phytochemicals are now increasingly exploited as remedial agents for the management of diabetes due to side effects attributable to commercial antidiabetic agents. This study investigated the structural and molecular mechanisms by which betulinic acid exhibits its antidiabetic effect via in vitro and computational techniques. In vitro antidiabetic potential was analysed via on α-amylase, α-glucosidase, pancreatic lipase and α-chymotrypsin inhibitory assays. Its structural and molecular inhibitory mechanisms were investigated using Density Functional Theory (DFT) analysis, molecular docking and molecular dynamics (MD) simulation. Betulinic acid significantly (p < 0.05) inhibited α-amylase, α-glucosidase, pancreatic lipase and α-chymotrypsin enzymes with IC50 of 70.02 µg/mL, 0.27 µg/mL, 1.70 µg/mL and 8.44 µg/mL, respectively. According to DFT studies, betulinic acid possesses similar reaction in gaseous phase and water due to close values observed for highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LUMO) and the chemical descriptors. The dipole moment indicates that betulinic acid has high polarity. Molecular electrostatic potential surface revealed the electrophilic and nucleophilic attack-prone atoms of the molecule. Molecular dynamic studies revealed a stable complex between betulinic acid and α-amylase, α-glucosidase, pancreatic lipase and α-chymotrypsin. The study elucidated the potent antidiabetic properties of betulinic acid by revealing its conformational inhibitory mode of action on enzymes involved in the onset of diabetes.

Antisickling effect of chrysin is associated with modulation of oxygenated and deoxygenated haemoglobin via alteration of functional chemistry and metabolic pathways of human sickle erythrocytes.

Sickle cell disease (SCD) treatment and management remain a challenging puzzle especially among developing Nations. Chrysin's sickling-suppressive properties in human sickle (SS) erythrocytes in addition to its effect on AA-genotype erythrocytes were evaluated. Sickling was induced (76%) with 2% sodium metabisulphite at 3 h. Chrysin prevented (81.19%) the sickling and reversed same (84.63%) with strong IC50s (0.0257 µM and 0.00275 µM, respectively). The levels of oxygenated haemoglobin in the two groups (before and after induction approaches) were similar but significantly (P < 0.05) higher than that of SS erythrocytes (the 'induced' control), with chrysin-treated AA-genotype showing no effects relative to the untreated. The level of deoxygenated haemoglobin in the 'induced' control group was significantly (P < 0.05) higher than those of the chrysin-treated SS erythrocytes. Normal and chrysin-untreated erythrocytes (AA-untreated) were significantly more resistant to osmotic fragility than the SS-untreated. However, treatment with chrysin significantly reduced the osmotic fragility of the cells relative to the untreated cells. Furthermore, chrysin treatment significantly lowers the high level of 2,3-diphosphoglycerate (2,3-DPG) observed in the sickle erythrocytes, with no effects on AA-genotype erythrocytes. Based on functional chemistry, chrysin treatment alters the functional groups in favour of its antisickling effects judging from the observed bends and shifts. From metabolomics analysis, it was observed that chrysin treatment favors fatty acid alkyl monoesters (FAMEs) production with concomitant shutting down-effects on selenocompound metabolism. Thus, sickling-suppressive effects of chrysin could potentially be associated with modulation of oxygenated and deoxygenated haemoglobin via alteration of human sickle erythrocyte's functional chemistry and metabolic pathways implicated in SCD crisis.

Neurotoxicity in pre-eclampsia involves oxidative injury, exacerbated cholinergic activity and impaired proteolytic and purinergic activities in cortex and cerebellum.

Women with a history of pre-eclampsia (PE) tend to have a higher risk of developing cardiovascular and neurological diseases later in life. Imbalance in oxidative markers and purinergic enzymes have been implicated in the pathogenesis of neurological disease. This study investigated the effect of PE on oxidative imbalance, purinergic enzyme inhibitory activity, acetylcholinesterase and chymotrypsin activities in the brain of PE rat model at post-partum/post-natal day (PP/PND) 60. Pregnant rats divided into early-onset and late-onset groups were administered with Nω-nitro-l-arginine methyl through drinking water at gestational days 8-17. Rats were allowed free access to water throughout the pregnancy and allowed to deliver on their own. The mother and the pups were euthanized at PP and PND 60, respectively, the cortex and the cerebellum excised, homogenized and stored for analyses of the enzymes. Results showed an increase in nitric oxide and malondialdehyde with a concomitant decrease in reduced glutathione and superoxide dismutase, an indication of oxidative damage. Also, there was an increase in acetylcholinesterase activity with a decrease in chymotrypsin, adenylpyrophosphatase and ecto-nucleoside triphosphate diphosphohydrolase activities in both the cortex and the cerebellum of the mother and the pups at PND 60. These results indicate the involvement of oxidative stress, increased cholinergic activity and depleted proteolytic and purinergic activities in PE-induced neurotoxicity.

Methanolic extract of Celosia argentea var. crista leaves modulates glucose homeostasis and abates oxidative hepatic injury in diabetic rats.

Celosia argentea commonly known as cockscomb plant is widely used in folkloric medicine in the treatment and management of diabetes mellitus. The effect of methanolic extract of Celosia argentea var. cristata L. (CAVCL) leaves on blood glucose level, superoxide dismutase (SOD), catalase (CAT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities, and malondialdehyde (MDA) level were evaluated in diabetic rats. Five groups of male albino rats consisting of 5 animals each were used for the present study. They were grouped as normal control, diabetic control, diabetic administered with 250 and 750 mg/kg b.w C. argentea, and 5 mg/kg b.w glibenclamide. Diabetes was induced with alloxan monohydrate intraperitoneally at 120 mg/kg b.w. The control and diabetic groups were given distilled water and rat chow for 21 days. Blood glucose level of each group was estimated every week, and at the end of the experiment, SOD, CAT, MDA and serum ALP, and AST and ALT activities were assayed in the liver and serum respectively of the experimental animals. The results showed a significant increase (p < 0.05) in serum AST, ALP, and ALT activities and reduction in SOD and CAT activities compared with normal control groups. The extract at both doses significantly lowered the high levels of the serum enzymes and increased the level of CAT and SOD. These results indicate an anti-hyperglycemia and antioxidative protective effect of C. argentea leaves.

Monodora myristica (African nutmeg) modulates redox homeostasis and alters functional chemistry in sickled erythrocytes.

The antioxidative effect of Monodora myristica seed acetone extract and its effect on chemical functional groups were investigated in sickled erythrocytes as well as molecular modeling of the antisickling potentials of its secondary metabolites. The extract was subjected to gas chromatography-mass spectrometry to identify the compounds present, which were then docked into the allosteric-binding site of deoxy-hemoglobin. The extract was incubated with sickled erythrocytes at 37°C for 6, 12, and 24 h and were subjected to antioxidative analysis for reduced glutathione (GSH), superoxide dismutase (SOD), catalase, and lipid peroxidation (LPO). Chemical functional group of the treated cells was analyzed via Fourier transform infrared spectroscopy (FTIR). The predominant compounds identified were 17-octadecynoic acid; oleic acid, androstan-3-one, 17-hydroxy-2-methyl- (2.beta.,5.beta.,17.beta.)-; estran-3-one, 17-(acetyloxy)-2-methyl-, (2.alpha., 5.alpha., 17.beta.), and (+)-3-carene, 10-(acetylmethyl)-. They all fitted well within the active site of Hb with good binding affinity, as evidenced by the negative CDocker interaction energies of their complexes ranging between -54.4 and -26.7 kcal/mol. Treatment with the extract exacerbated SOD and catalase activities as well as GSH level, while LPO was suppressed. This antioxidative activity was time and/or dose dependent, with 6 and 12 h incubation showing the optimum activity. FTIR analysis of the treated cells showed the presence of hydrophobic functional groups. The synergetic molecular interaction of the major compounds of the extract with the α-dimer of Hb depicts an antisickling effect of M. myristica acetone extract. This is accompanied by exacerbation of endogenous antioxidant enzymes activity and modification of the functional chemistry of the cells.

Alteration of redox status by commonly used antimalarial drugs in the north-western region of Nigeria.

This study was designed to investigate the alteration of redox status by commonly used antimalarials in Nigeria. Drugs used were artemisinin, artesunate, chloroquine, coartem and quinine at the final concentrations of 0.5-8.0 mg/mL. Blood samples were collected from malarial patients and apparently healthy humans for comparison. Reduced glutathione, catalase, superoxide dismutase (SOD) activities, protein content and lipid peroxidation were determined. All drugs significantly ( p < 0.05) increases the protein level relative to control in normal blood, whereas in the infected, a significant ( p < 0.05) reduction was observed. In normal blood, the antimalarials dose dependently decreased ( p < 0.05) SOD and catalase activities with significant ( p < 0.05) increase in the infected. The level of glutathione in normal blood significantly ( p < 0.05) increases as compared with control, whereas in the infected, similar observation was made except that the levels were less, relative to control sample. Malondialdehyde level significantly ( p < 0.05) increases with increase in drugs concentration even though less than the level in the control with few exceptions. These effects were dose dependent and more pronounced in non-malarial conditions. Commonly used antimalarials might alter the redox status in both healthy and non-healthy subjects thereby inducing oxidative stress.

Effect of pineapple peel extract on total phospholipids and lipid peroxidation in brain tissues of rats.

OBJECTIVE: To investigate the ability of the methanolic extract of pineapple peel to attenuate alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues. METHODS: Oxidative stress was induced by oral administration of ethanol (20% w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Brain tissues were assayed for total phospholipid (TP) content and malondialdehyde (MDA). RESULTS: Administration of alcohol significantly caused a reduction in TP content. Treatment with pineapple peel extract significantly increased the TP content. Significant high levels of MDA was observed in alcohol-fed rats, treatment with pineapple peel extract significantly reduced the MDA levels. CONCLUSIONS: Results obtained from this study indicates that pineapple peel extract protects against alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues.

Modulatory effect of pineapple peel extract on lipid peroxidation, catalase activity and hepatic biomarker levels in blood plasma of alcohol-induced oxidative stressed rats.

OBJECTIVE: To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation, changes in catalase activities and hepatic biochemical marker levels in blood plasma. METHODS: Oxidative stress was induced by oral administration of ethanol (20% w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3 000 rpm for 10 min. The plasma was analyzed to evaluate malondialdehyde (MDA), catalase activity, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations. RESULTS: Administration of alcohol caused a drastic increase (87.74%) in MDA level compared with the control. Pineapple peel extract significantly reduced the MDA level by 60.16% at 2.5 mL/kg bw. Rats fed alcohol only had the highest catalase activity, treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity. Increased AST, ALP and ALT activities were observed in rats fed alcohol only respectively, treatment with pineapple peel extract drastically reduced their activities. CONCLUSIONS: The positive modulation of lipid peroxidation, catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcohol-induced oxidative stress is an indication of its protective ability in the management of alcohol-induced toxicity.