Hepatoprotective and antioxidant effi cacy of aqueous stem bark extracts of Balanites aegyptiaca (Linn.) Del. against acetaminophen induced liver injury in rats

Traditional use of various extracts of Balanites aegyptiaca in the management of many diseases has been previouslyreported. Though oxidative stress is known to contribute to the development of many of the disease conditionson which extracts of B. aegytiaca have been found efficacious, effects of these extracts on free radical-inducedlipid peroxidation is not well understood. This study investigated the protective effects of stem bark extracts ofB. aegyptiaca on acetaminophen-induced lipid peroxidation in rats. Phytochemical analysis of the plant extract usedwas conducted. Following a 10 day pre-treatment with extracts of B. aegyptiaca, serum levels of thiobarbituricreactive substances (TBARS), vitamin C, cholesterol/phospholipids, catalase (CAT) activity as well as markersenzymes of hepatotoxicity were measured in rats administered with acetaminophen (2 mg/kg body weight).Results obtained indicated preponderance of alkaloids, flavonoids, glycosides, phenols, saponins, and tannins.Pre-treatment with extracts of B. aegyptiaca protected against acetaminophen-induced elevation of TBARS andmarker enzymes of hepatotoxicity as well as inhibited the depletion of serum levels of vitamin C, CAT activity andphospholipids in a dose-dependent manner. Serum levels of cholesterol were not affected by acetaminophenintoxication or treatment with the plant extract. These results indicated that therapeutic actions previouslylinked with extracts of B. aegyptiaca might be a consequence of its antioxidative and hepatoprotective effects

Extracts of Jatropha curcas L. exhibit significant insecticidal and grain protectant effects against maize weevil, Sitophilus zeamais (Coleoptera: Curculionidae)

Phytochemical composition of leaf extracts as well as biological effects of juice, leaf extracts and seed oil of Jatropha curcas against Sitophilus zeamis were examined. The study also investigated the inhibition of oviposition, progeny production and grain damage, insecticidal effects and mammalian toxicity of the extracts. Compared to other phytochemicals, the concentration of saponin and cardiac glycoside were higher in the leaf extract. All extracts of J. curcas (0 – 100 ppm) investigated showed a dose-dependent inhibition of ovisposition, progeny production and promote significant (P < 0.001) insect mortality. Grains pre-treated with seed oil produced the highest result for all the parameters. The seed oil (100 ppm) produced 93% (P < 0.001) protection against grain damage by Sitophilus zeamis. Observable physical deformities were observed in rats administered with graded doses of the seed oil as opposed to other extracts. Administration of a single dose of the extracts produced significant (P < 0.01) elevation of serum level of alanine (ALT) and aspartic (AST) transaminases and alkaline phosphatase (ALP) in rats.Published onlin

Antidiabetic activities of chloroform fraction of Anthocleista vogelii Planch root bark in rats with diet- and alloxan-induced obesity-diabetes

ETHNOPHARMACOLOGICAL RELEVANCE: Anthocleista vogelii Planch is a medicinal plant traditionally used in West Africa for the management and treatment of diabetes mellitus. AIM OF THE STUDY: To determine the antidiabetic activities of chloroform fraction (CF) of Anthocleista vogelii Planch root bark in rats with diet- and alloxan-induced obesity-diabetes. MATERIALS AND METHODS: Inhibitory activities of CF against α-amylase and α-glucosidase activities were determined in vitro. Three weeks old rats were fed with high-fat diet for 9 weeks to induce obesity prior to further induction of diabetes using alloxan (150 mg/kg body weight, i.p.). Blood glucose levels and body weight were measured every 7 days throughout the experiment. Glucose tolerance was assessed in normal and CF-treated rats on day 21. Terminal blood samples were collected from sacrificed animals for the measurement of serum insulin levels. Pancreases were excised from treated and untreated animals for histopathological examination. RESULTS: LCMS/MS chromatographic profile of CF via positive and negative modes revealed 13 and 23 compounds respectively. Further analysis revealed quebrachitol (QCT), loganin, sweroside, oleoside 11-methyl ester and ferulic acid, which have been previously reported for their antidiabetic activities, as constituents of CF. CF inhibited activities of α-amylase (IC50 = 51.60 ± 0.92 µg/ml) and α-glucosidase (IC50 = 5.86 ± 0.97 µg/ml) in a dose-dependent manner. Treatment of animals with obesity-diabetes with 100 and 200 mg/kg CF significantly improved glucose tolerance (P < 0.001) and enhanced serum insulin levels (P < 0.05) compared to diabetic control rats. CONCLUSIONS: Antidiabetic activities of CF might be mediated via inhibition of α-amylase and α-glucosidase activities, elevation of serum insulin concentration, and enhancement of insulin and leptin sensitivity in obesity-diabetes rats. This study further substantiates the traditional use of A. vogelii in the management and treatment of diabetes in Africa and encourages further studies to investigate its mechanism of action

Computational Biology and Bioinformatics in Nigeria

Over the past few decades, major advances in the field of molecular biology, coupled with advances in genomic technologies, have led to an explosive growth in the biological data generated by the scientific community. The critical need to process and analyze such a deluge of data and turn it into useful knowledge has caused bioinformatics to gain prominence and importance. Bioinformatics is an interdisciplinary research area that applies techniques, methodologies, and tools in computer and information science to solve biological problems. In Nigeria, bioinformatics has recently played a vital role in the advancement of biological sciences. As a developing country, the importance of bioinformatics is rapidly gaining acceptance, and bioinformatics groups comprised of biologists, computer scientists, and computer engineers are being constituted at Nigerian universities and research institutes. In this article, we present an overview of bioinformatics education and research in Nigeria. We also discuss professional societies and academic and research institutions that play central roles in advancing the discipline in Nigeria. Finally, we propose strategies that can bolster bioinformatics education and support from policy makers in Nigeria, with potential positive implications for other developing countries. © 2014 Fatumo et al.SAF was supported by H3ABioNet NABDA Node, Abuja, Nigeria with NIH Common Fund Award/NHGRI Grant Number U41HG006941 and Genetic Epidemiology Group at Wellcome Trust Sanger Institute.Published versio

In vitro and in vivo insulinotropic properties of the multifunctional frog skin peptide hymenochirin-1B: a structure–activity study

Hymenochirin-1b (Hym-1B; IKLSPETKDNLKKVLKGAIKGAIAVAKMV.NH2) is a cationic, α-helical amphibian host-defense peptide with antimicrobial, anticancer, and immunomodulatory properties. This study investigates the abilities of the peptide and nine analogues containing substitutions of Pro5, Glu6, and Asp9 by either l-lysine or d-lysine to stimulate insulin release in vitro using BRIN-BD11 clonal β cells or isolated mouse islets and in vivo using mice fed a high-fat diet to produce obesity and insulin resistance. Hym-1B produced a significant and concentration-dependent increase in the rate of insulin release from BRIN-BD11 cells without cytotoxicity at concentrations up to 1 µM with a threshold concentration of 1 nM. The threshold concentrations for the analogues were: [P5K], [E6K], [D9K], [P5K, E6K] and [E6K, D9k] 0.003 nM, [E6K, D9K] and [D9k] 0.01 nM, [P5K, D9K] 0.1 nM and [E6k] 0.3 nM. All peptides displayed cytotoxicity at concentrations ≥1 µM except the [P5K] and [D9k] analogues which were non-toxic at 3 µM. The potency and maximum rate of insulin release from mouse islets produced by the [P5K] peptide were significantly greater than produced by Hym-1B. Neither Hym-1B nor the [P5K] analogue at 1 µM concentration had an effect on membrane depolarization or intracellular Ca2+. The [P5K] analogue (1 µM) produced a significant increase in cAMP concentration in BRIN-BD11 cells and stimulated GLP-1 secretion from GLUTag cells. Down-regulation of the protein kinase A pathway by overnight incubation with forskolin completely abolished the insulin-releasing effects of [P5K]hym-1B. Intraperitoneal administration of the [P5K] and [D9k] analogues (75 nmol/kg body weight) to high-fat-fed mice with insulin resistance significantly enhanced glucose tolerance with a concomitant increase in insulin secretion. We conclude that [P5K]hym-1B and [D9k]hym-1B show potential for development into anti-diabetic agents

Possible association between ABCC8 C49620T polymorphism and type 2 diabetes in a Nigerian population

The association between ABCC8 gene C49620T polymorphism and type 2 diabetes (T2D) in populations of diverse ethnic backgrounds has been reported. However, such occurrence in an African population is yet to be established. This case-control study involving 73 T2D and 75 non-diabetic (ND) patients investigated the occurrence of this polymorphism among T2D patients in Nigeria and assessed its relationship with body lipids of patients. Demographic and clinical characteristics of patients were collected and lipid profile indices including total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) were assayed. Restriction fragment length polymorphism-PCR (RFLP-PCR) was employed to genotype the ABCC8-C49620T polymorphism using PstI restriction enzyme. This study revealed significantly (p 0.05) of T2D for the unadjusted codominant, dominant and recessive models. Following age adjustment, the mutant genotypes (CT and TT) showed significant (p<0.05) risk of T2D for all the models with the recessive model presenting the greatest risk of T2D (OR: 2.39, 95% CI: 1.16-4.91, p<0.018). The TT genotype significantly (p<0.05) associated with high level of HDL and reduced levels of TC, TG and LDL in non-diabetic patients but was not associated with any of the demographic and clinical characteristics among T2D patients. ABCC8 C49620T polymorphism showed possible association with T2D marked by predominance of the mutant TT genotype in T2D patients. However, the relationship between TT genotype and lipid abnormalities for possible beneficial effect on people suffering from T2D is unclear

Evidence for Involvement of GIP and GLP-1 Receptors and the Gut-Gonadal Axis in Regulating Female Reproductive Function in Mice.

Funder: Biotechnology and Biological Sciences Research CouncilSubstantial evidence suggests crosstalk between reproductive and gut-axis but mechanisms linking metabolism and reproduction are still unclear. The present study evaluated the possible role of glucose-dependent-insulinotropic-polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1) in reproductive function by examining receptor distribution and the effects of global GIPR and GLP-1R deletion on estrous cycling and reproductive outcomes in mice. GIPR and GLP-1R gene expression were readily detected by PCR in female reproductive tissues including pituitary, ovaries and uterine horn. Protein expression was confirmed with histological visualisation of incretin receptors using GIPR-Cre and GLP1R-Cre mice in which the incretin receptor expressing cells were fluorescently tagged. Functional studies revealed that female GIPR-/- and GLP-1R-/- null mice exhibited significantly (p < 0.05 and p < 0.01) deranged estrous cycling compared to wild-type controls, indicative of reduced fertility. Furthermore, only 50% and 16% of female GIPR-/- and GLP-1R-/- mice, respectively produced litters with wild-type males across three breeding cycles. Consistent with a physiological role of incretin receptors in pregnancy outcome, litter size was significantly (p < 0.001-p < 0.05) decreased in GIPR-/- and GLP-1R-/- mice. Treatment with oral metformin (300 mg/kg body-weight), an agent used clinically for treatment of PCOS, for a further two breeding periods showed no amelioration of pregnancy outcome except that litter size in the GIPR-/- group was approximately 2 times greater in the second breeding cycle. These data highlight the significance of incretin receptors in modulation of female reproductive function which may provide future targets for pharmacological intervention in reproductive disorders

The impact of vitamin D deficiency on patients undergoing kidney transplantation: focus on cardiovascular, metabolic, and endocrine outcomes

Vitamin D deficiency is common among kidney transplant (KT) recipients because of reduced sunlight exposure, low intake of vitamin D, the immunosuppressive drug regimen administered, and steroid therapy. Glucocorticoids regulate expression of genes coding for enzymes that catabolize vitamin D, further reducing its level in serum. Although vitamin D primarily regulates calcium homeostasis, vitamin D deficiency is associated with the risk of several diseases, such as diabetes mellitus and tuberculosis. Aim of this review is to highlight endocrine and metabolic alterations due to the vitamin D deficiency by evaluating the mechanisms involved in the development of KT-related disease (cardiovascular, bone mineral density, and new-onset diabetes after transplantation). Next, we review evidence to support a link between low vitamin D status and KT-related diseases. Finally, we briefly highlight strategies for restoring vitamin D status in KT patients

Molecular mechanisms mediating the beneficial metabolic effects of [Arg4]tigerinin-1R in mice with diet-induced obesity and insulin resistance

AbstractThe frog skin host-defense peptide tigerinin-1R stimulates insulin releasein vitroand improves glucose tolerance and insulin sensitivity in animal models of type 2 diabetes. This study extends these observations by investigating the molecular mechanisms of action underlying the beneficial metabolic effects of the analogue [Arg4]tigerinin-1R in mice with diet-induced obesity, glucose intolerance and insulin resistance. The study also investigates the electrophysiological effects of the peptide on KATPand L-type Ca2+channels in BRIN-BD11 clonal β cells. Non-fasting plasma glucose and glucagon concentrations were significantly (p&lt;0.05) decreased and plasma insulin increased by twice daily treatment with [Arg4]tigerinin-1R (75 nmol/kg body weight) for 28 days. Oral and intraperitoneal glucose tolerance were significantly (p&lt;0.05) improved accompanied by enhanced secretion and action of insulin. The peptide blocked KATPchannels and, consistent with this, improved beta cell responses of isolated islets to a range of secretagogues. Peptide administration resulted in up-regulation of key functional genes in islets involved insulin secretion (Abcc8, Kcnj11, Cacna1candSlc2a2) and in skeletal muscle involved with insulin action (Insr, Irs1, Pdk1,Pik3ca,andSlc2a4). These observations encourage further development of tigerinin-1R analogues for the treatment of patients with type 2 diabetes.</jats:p

Esculentin-2CHa-Related Peptides Modulate Islet Cell Function and Improve Glucose Tolerance in Mice with Diet-Induced Obesity and Insulin Resistance

<div><p>The frog skin host-defense peptide esculentin-2CHa (GFSSIFRGVA¹⁰KFASKGLGK D²⁰LAKLGVDLVA³⁰CKISKQC) displays antimicrobial, antitumor, and immunomodulatory properties. This study investigated the antidiabetic actions of the peptide and selected analogues. Esculentin-2CHa stimulated insulin secretion from rat BRIN-BD11 clonal pancreatic β-cells at concentrations greater than 0.3 nM without cytotoxicity by a mechanism involving membrane depolarization and increase of intracellular Ca²⁺. Insulinotropic activity was attenuated by activation of K_ATP channels, inhibition of voltage-dependent Ca²⁺ channels and chelation of extracellular Ca²⁺. The [L21K], [L24K], [D20K, D27K] and [C31S,C37S] analogues were more potent but less effective than esculentin-2CHa whereas the [L28K] and [C31K] analogues were both more potent and produced a significantly (P < 0.001) greater maximum response. Acute administration of [L28K]esculentin-2CHa (75 nmol/kg body weight) to high fat fed mice with obesity and insulin resistance enhanced glucose tolerance and insulin secretion. Twice-daily administration of this dose of [L28K]esculentin-2CHa for 28 days had no significant effect on body weight, food intake, indirect calorimetry or body composition. However, mice exhibited decreased non-fasting plasma glucose (P < 0.05), increased non-fasting plasma insulin (P < 0.05) as well as improved glucose tolerance and insulin secretion (P < 0.01) following both oral and intraperitoneal glucose loads. Impaired responses of isolated islets from high fat fed mice to established insulin secretagogues were restored by [L28K]esculentin-2CHa treatment. Peptide treatment was accompanied by significantly lower plasma and pancreatic glucagon levels and normalization of α-cell mass. Circulating triglyceride concentrations were decreased but plasma cholesterol and LDL concentrations were not significantly affected. The data encourage further investigation of the potential of esculentin-2CHa related peptides for treatment of patients with type 2 diabetes.</p></div