Possible involvement of sialidase and sialyltransferase activities in a stage-dependent recycling of sialic acid in some organs of type 1 and type 2 diabetic rats.

Background: Type 1 (T1D) and type 2 (T2D) diabetes lead to an aberrant metabolism of sialoglycoconjugates and elevated free serum sialic acid (FSSA) level. The present study evaluated sialidase and sialyltranferase activities in serum and some organs relevant to diabetes at early and late stages of T1D and T2D. Methods: Sialic acid level with sialidase and sialyltransferase activities were monitored in the serum, liver, pancreas, skeletal muscle and kidney of diabetic animals at early and late stages of the diseases. Results: The FSSA and activity of sialidase in the serum were significantly increased at late stage of both T1D and T2D while sialic acid level in the liver was significantly decreased in the early and late stages of T1D and T2D, respectively. Furthermore, the activity of sialidase was significantly elevated in most of the diabetes-relevant organs while the activity of sialyltransferase remained largely unchanged. A multiple regression analysis revealed the contribution of the liver to the FSSA while pancreas and kidney contributed to the activity of sialidase in the serum. Conclusions: We concluded that the release of hepatic sialic acid in addition to pancreatic and renal sialidase might (in)directly contribute to the increased FSSA during both types of diabetes mellitus.

Elevated serum sialic acids, a potent biomarker of alloxan-induced type 1 diabetes in dogs by ethanolic extract of Anogeissus leiocarpus.

OBJECTIVES: This study investigated serum sialic acids for a predictive and diagnostic biomarker of diabetes mellitus (DM) in dogs and its prognostic value with ethanolic extract of Anogeissus leiocarpus. DESIGN: Four groups of 3 dogs were used; non-diabetic controls (ND), diabetic-untreated (DU), diabetic insulin-treated (DI) and diabetic extract-treated (DE). Free serum sialic acids (FSSA) and erythrocyte surface sialic acids (ESSA) were assayed in all groups, pre-and post-induction of hyperglycaemia and results were presented as means ± standard error of means (SEM) and subjected to ANOVA using Tukey's post-hoc tests with GraphPad Prism® statistical package. RESULTS: FSSA increased in DU and plateaued at third week (61.8 ± 0.41 µg/ml), (P < 0.002) with additional 38.2 µg/ml (62%) generated, coinciding with hyperglycaemia. FSSA of DI increased but declined to 22.3 ± 1.55 µg/ml. Extract of Anogeissus leiocarpus effectively modulated FSSA in DE as increased value declined to 21.4 ± 0.78 µg/ml. Pre-induction DU ESSA (8.27 ± 0.11 µg/ml) significantly (P < 0.002) decreased by third week (2.33 ± 1.49 µg/ml), coinciding with hyperglycaemia. Strong negative correlation coefficient (r = -0.92) occurred between DU's FSSA and ESSA and ND (P < 0.03). Sialic acid expression in dog's insulin dependent diabetes mellitus (IDDM) is 18% lower than normal. Extract of A. leiocarpus restored ESSA completely. ESSA cleaved in DU, 5.94 µg/ml (72%), could not account for the extra FSSA (32.26 µg/ml); liver and kidneys are contributors. CONCLUSION: FSSA predicts canine DM.

Trypanosuppresive effects of ellagic acid and amelioration of the trypanosome-associated pathological features coupled with inhibitory effects on trypanosomal sialidase in vitro and in silico.

BACKGROUND: The search for novel antitrypanosomal agents had previously led to the isolation of ellagic acid as a bioactive antitrypanosomal compound using in vitro studies. However, it is not known whether this compound will elicit antitrypanosomal activity in in vivo condition which is usually the next step in the drug discovery process. PURPOSE: Herein, we investigated the in vivo activity of ellagic acid against bloodstream form of Trypanosoma congolense and its ameliorative effects on trypanosome-induced anemia and organ damage as well as inhibitory effects on trypanosomal sialidase. METHODS: Rats were infected with T. congolense and were treated with 100 and 200mg/kg body weight (BW) of ellagic acid for fourteen days. The levels of parasitemia, packed cell volume and biochemical parameters were measured. Subsequently, T. congolense sialidase was partially purified on DEAE cellulose column and the mode of inhibition of ellagic acid on the T. congolense sialidase determined. Molecular docking study was also conducted to determine the mode of interaction of the ellagic acid to the catalytic domain of T. rangeli sialidase. RESULTS: At a dose of 100 and 200mg/kg (BW), ellagic acid demonstrated significant (P < 0.05) trypanosuppressive effect for most of the 24 days experimental period. Further, the ellagic acid significantly (P < 0.05) ameliorated the trypanosome-induced anemia, hepatic and renal damages as well as hepatomegaly, splenomegaly and renal hypertrophy. The trypanosome-associated free serum sialic acid upsurge alongside the accompanied membrane bound sialic acid reduction were also significantly (P < 0.05) prevented by the ellagic acid treatment. The T. congolense sialidase was purified to a fold of 6.6 with a yield of 83.8%. The enzyme had a KM and Vmax of 70.12mg/ml and 0.04µmol/min respectively, and was inhibited in a non-competitive pattern by ellagic acid with an inhibition binding constant of 1986.75µM. However, in molecular docking study, ellagic acid formed hydrogen bonding interaction with major residues R39, R318, and W124 at the active site of T. rangeli sialidase with a predicted binding free energy of -25.584kcal/mol. CONCLUSION: We concluded that ellagic acid possesses trypanosuppressive effects and could ameliorate the trypanosome-induced pathological alterations.

Stigmasterol retards the proliferation and pathological features of Trypanosoma congolense infection in rats and inhibits trypanosomal sialidase in vitro and in silico.

Stigmasterol has been reported to possess antitrypanosomal activity using in vitro model but information on the in vivo antitrypanosomal effects which is necessary in drug development process has not been evaluated. Hence, the present study investigates the in vivo effects of stigmasterol against T. congolense in addition to its inhibitory effects of trypanosomal sialidase. Stigmasterol, at 100mg/kg BW, did not significantly (p>0.05) reduce the progression of T. congolense infection in animals but a 200mg/kg BW stigmasterol treatment significantly (p<0.05) reduced the parasitemia, although, it did not completely eliminate the parasite from the bloodstream of infected animals. However, the stigmasterol treatments significantly (p<0.05) ameliorated the T. congolense induced anemia as well as hepatic and renal damages. Furthermore, the T. congolense-associated increase in free serum sialic acid with a corresponding decrease in membrane bound sialic acid were prevented, though insignificantly (p>0.05), by the 200mg/kg BW treatment. Subsequently, in vitro enzyme kinetic studies revealed that stigmasterol is an uncompetitive inhibitor of a partially purified bloodstream T. congolense sialidase with an inhibition binding constant of 356.59µM. Using molecular docking studies, stigmasterol formed a single hydrogen bonding interaction with a major residue (D63) at the catalytic domain of T. rangeli sialidase with a predicted binding free energy of -24.012kcal/mol. We concluded that stigmasterol could retard the proliferation and the major pathological features of T. congolense infection whilst the anemia amelioration was mediated via inhibition of sialidase.

Sickled Erythrocytes Reversal and Membrane Stabilizing Compounds in Telfairia occidentalis.

Background and Purpose. Traditional management of sickle cell disease (SCD) is ubiquitous in Africa. In south-eastern Nigeria, Telfairia occidentalis (T. occidentalis) is strongly recommended for consumption by SCD patients, owing to its presumed therapeutic effect. This study investigates the antisickling and membrane regenerative potentials of T. occidentalis in sickled erythrocytes. Experimental Approach. Sickled erythrocytes obtained from SCD patients were treated with sodium metabisulphite (2%) to induce further sickling. Heat and hypotonic-induced lyses of red blood cells' membranes were also carried out. The RBCs were treated with varying concentration (10.0, 1.0, and 0.1 mg mL(-1) and 0.5, 1.0, 1.5, 2.0, and 2.5 mg mL(-1), resp.) of T. occidentalis extracts as treatment regimen for in vitro antisickling and membrane stabilizing assays. Extract with peak activity was purified and reused in antisickling assay. Key Results. The antisickling activity of aqueous and methanolic extracts of leaves, seeds, and stem of Telfairia occidentalis at 10.0, 1.0, and 0.1 mg mL(-1) revealed that the aqueous leaves extract (10 mg mL(-1)) exhibited the highest antisickling activity (64.03%) which was significantly (p < 0.05) higher than that of the stem (47.30%) and seeds (37.50%). Partially purified fractions recorded improved antisickling effect (peak activity of 70%). Characterization (using GC-MS) of the most active fraction revealed some bioactive compounds. In the membrane stabilizing assay, methanolic and aqueous stem extracts of T. occidentalis showed the highest effect of 71.85% and 61.29%, respectively. Conclusions and Implications. The results provide scientific evidence for ethnopharmacological use of T. occidentalis in the management of SCD.

Effects of aqueous extracts of Acacia albida stem bark on Wistar albino rats infected with Trypanosoma evansi.

The effect of aqueous extract of Acacia albida stem bark was investigated in Wistar albino rats infected with Trypanosoma evansi. The extract showed highest reduction in parasitemia at the dose of 600 mg/kg body weight (bw). A dose of 300 mg/kg bw improved packed cell volume the most by 14.35%. The group treated with 150 and 600 mg/kg bw of the extract showed significant decrease (P < 0.05) in alanine transaminase and aspartate transaminase levels which were lower than those of the group treated with diminazene aceturate. The group treated with 150 mg/kg bw of the extract showed the least urea, albumin and protein level and lowest relative organ weight. There was a significant difference (P < 0.05) in the levels of catalase and Thiobarbituric acid reactive substances in liver and kidney of the animals in the infected-untreated group and the extracts-treated groups. The results of this study show that the extracts of A. albida have antitrypanosomal activity against T. evansi infection.

Socio-economic status of patients with type 2 diabetes and hypertension attending the Ahmadu Bello University Teaching Hospital, Zaria, North-West Nigeria.

Hypertension (HTN) and Type 2 diabetes (T2D) are lifestyle interrelated diseases of global significance. Interestingly, the prevalence of these diseases in Africa and indeed Nigeria seems to be on the increase. This study, therefore, investigated the socioeconomic status (based on income, education and occupational activity) of 400 subjects (52% female and 48% male) aged 20 years and above who were sampled randomly among the newly diagnosed HTN and/or T2D cases at the Ahmadu Bello University Teaching Hospital, Zaria, North-West Nigeria. A semi-structured questionnaire was used to collect information from the subjects. From the result obtained, most of the respondents who live in towns or city suffer from either HTN or T2D while more town dwellers (28%) suffer from a combination of both diseases. It was also discovered that most respondents who suffer from HTN and from a combination of HTN and T2D belong to the old generation (60-79 years). There is higher prevalence rate of diabetes among the respondents who had no formal education or attended only basic Arabic schools. Most respondents who earn good income (NGN50,000-NGN100,000 and above NGN100,000) suffer HTN, T2D and a combination of both diseases. Those engaged in heavy occupational activities had the lowest prevalence of the disease compared with those of light or moderate occupational activities. These data will be found useful in planning intervention healthcare preventive programs especially on public enlightenment workshops and seminars to educate the populace on the importance of lifestyle modification, healthy diet and regular exercises.

Bio-content of Telferia occidentalis and their effect on methemoglobin formation in sickled erythrocytes

Objective: To perform phytochemical and mineral analyses on leaves, stem and seeds of Telferia occidentalis (T. occidentalis), and examine the inhibition of methemoglobin build-up in sickled erythrocytes. Methods: The phytochemical evaluation was carried out by qualitative and quantitative analyses, whereas mineral elements were quantitatively analyzed. The effect of T. occidentalis on methemoglobin formation in sickled erythrocytes was examined using the ratio of ferric ion (Fe

Bio-content of Telferia occidentalis and their effect on methemoglobin formation in sickled erythrocytes

OBJECTIVE@#To perform phytochemical and mineral analyses on leaves, stem and seeds of Telferia occidentalis (T. occidentalis), and examine the inhibition of methemoglobin build-up in sickled erythrocytes.@*METHODS@#The phytochemical evaluation was carried out by qualitative and quantitative analyses, whereas mineral elements were quantitatively analyzed. The effect of T. occidentalis on methemoglobin formation in sickled erythrocytes was examined using the ratio of ferric ion (Fe(2+)) to ferrous ion (Fe(3+)) concentration, as index.@*RESULTS@#The phytochemical evaluation showed the presence of total phenolics, cyanogenic glycosides, flavonoids and alkaloids. Mineral analysis revealed potassium, magnesium, sodium, iron and zinc. Extract concentrations (0.2%-0.8% w/v) of leaves, seeds and stem of T. occidentalis have shown the ability to inhibit the formation of methemoglobin in sickled erythrocytes. The methanolic leaves extract showed the highest effect at 0.8% w/v.@*CONCLUSIONS@#These results suggest that T. occidentalis has the capacity to mop-up methemoglobin in sickled erythrocytes, and may therefore enhance oxygen-hemoglobin binding and transport in sickle cell disease patients.