Aims: It has been repored that neuropeptide Y receptor Y2 (Y2R) is involved in stress- and high caloric diet-induced metabolic syndrome in mice. Our previous report indicated the association between SNPs of Y2R gene upstream and plasma HDL-cholesterol levels in healthy subjects (rs6857530: GG<GA<AA or rs6857715: TT<TC<CC). Human macrophage differentiated from THP-
1 cells revealed the luciferase activity when transfected with pGL3 -Basic vector inserted by promoter region of Y2R containing rs6857530AA plus rs6857715CC but not by rs6857530GG plus rs6857715TT. This study was carried out to clarify the mechanism of the association between SNPs of Y2R gene upstream and plasma HDL-cholesterol levels.
Methodology: Y2R gene upstream included heterozygous rs6857530 (G/A) and rs6857715 (T/C) in macrophage/THP-1 cells by direct sequencing. Thus, the experiment was carried out to investigate the effect of potent Y2R antagonist BIIE0246 on gene expression in cultured macrophage/THP-1 cells using microarray.
Results: BIIE0246 up-regulated 60 transcripts (>2.0-fold) and down-regulated 55 entities (<0.5-fold) among 60,000 probe sets. It is of interest that leptin receptor gene was up-regulated (2.83-fold) by BIIE0246. BIIE0246-induced up- and down-regulation of gene expression indicated 6 and 1 gene ontology terms, respectively (P<0.001), and 7 pathways including leptin signaling and 1 pathway, respectively (P<0.01).
Conclusion: BIIE0246 regulated several genes and pathways including leptin signaling in macrophage/THP-1 cells. Taken together with the previous report by others, NPY might stimulate cholesterol efflux through Y2R by inhibiting leptin signaling in macrophage/THP-1 cells. Results were consistent with our previous reports indicating higher plasma HDL-cholesterol levels in subjects with Y2R expressive SNPs rs6857530AA plus rs6857715CC in macrophage.
Assessing the inhibitory activities of Telfairia occidentalis, Murraya koenigii, Hibiscus cannabinus and Vernonia amygdalina on α-amylase with the view of providing a sustainable remedies for the management of diabetes mellitus was conducted. Findings from In vitro studies showed that the ethanolic extracts (at a concentration of 10 – 100 µg/ml) of Vernonia amygdalina, Telfairia occidentalis, Murraya koenigii and Hibiscus cannabinus exerted a maximum percentage inhibition on α-amylase at 74.28, 64.87, 58.60 and 71.20 respectively; with IC50 of 10.70 µg/ml, 680 µg/ml, 62.62 µg/ml and 30.0 µg/ml when compared with the standard drug. In vivo studies also showed that hypoglycaemic activity of ethanolic extracts of Vernonia amygdalina, Telfairia occidentalis, Murraya koenigii and Hibiscus cannabinus on oral administration (400 mg/Kg b.w) on alloxan induced diabetes albino rats significantly (P˂0.05) improved body weight and significantly decrease blood glucose levels (P˂0.05). This suggest among others that these plants have the potential of being is a promising adjuncts for the management of diabetes in lowering post prandial hyperglycaemia. In vivo studies further shows that Murraya koenigii, and Vernonia amygdalina leaves could be important in the management of diabetes mellitus as results indicated a competing hypoglycaemic activity with the standard drug (Acarbose). The implication of adopting the extracts of these plants in the design of cost friendly drugs with minimal side effects for diabetes mellitus was discussed.
Aims: This hospital based case-control study sought to analyze the association between the promoter region polymorphism in TNF-α and the risks of developing end stage renal disease in nephropathy subjects.
Methodology: 222 documented cases of end stage renal disease (Males=148, Females=74) subjects and 250 healthy controls (Males=130, Females=120) were included in the study. Among 222 cases, 126 subjects had hypertensive nephropathy and 96 had glomerulonephritis as contributing factors of ESRD. Clinical and demographic data was collected from each case. TNF-α (-308 G→A) promoter polymorphism was analyzed by selective amplification by polymerase chain reaction and subsequent digestion by NcoI restriction enzyme. Genotypic and allelic frequencies were compared to controls using Chi-square and Odds ratio analysis. Clinical parameters were compared across genotypes using logistic regression. The probability values were adjusted for age and gender.
Results: Mean age of cases and controls was 47.78 and 46.83 years respectively. Genotypes for TNF-α -308 followed Hardy Weinberg equilibrium (P=0.17). The frequency of homozygous wild, heterozygous and homozygous rare genotypes in cases and controls was 62.6%, 31.08%, 6.3% and 74%, 23.6%, 2.4% respectively (P=0.019). Comparison of genotypes between cases and controls showed an association of AA genotype with ESRD (P=0.02, OR=3.1, 95%CI=1.1-6.2). The AA genotype was significantly associated with lower age in cases (P=0.008) as well as lower serum protein (P=0.03) and calcium levels (P=0.01).
Conclusion: TNF-α (-308 G→A) promoter polymorphism is associated with nephropathy and the carriers of AA genotype exhibit an increased risk towards rapid progression of ESRD.
The catalytic activities and kinetic parameters of the enzyme peroxidase (POX), extracted from two plant species namely Rosmarinus officinalis and Eruca sativa, were investigated in the presence and absence of various heavy metals. The activation effects of heavy metals Co2+, Fe3+ and Pb2+ have performed a noncompetitive inhibition on the enzyme activity in the crude extract of Eruca sativa. In contrast, Cd2+, Ni+ and Cu2+ have an uncompetitive inhibition for the two selected plants. Furthermore, Fe3+, Al3+, Pb2+ and Mo2+ were found to be acted as noncompetitive inhibitors on the enzyme activity in the crude extract of Rosmarinus officinalis. Presence of heavy metals altered the enzyme activity by acting as uncompetitive or noncompetitive inhibitors depending on the type of heavy metals.
Aim: Investigating and comparing the effect of administration of different preparations of the commonly-consumed Hibiscus sabdariffa (Zobo) drinks on hepatic and renal indices.
Study Design: Animal models (Wistar Albino Rats) with daily administration of the same concentration of different zobo drink samples.
Place and Duration of Study: University of Port Harcourt, Choba, Rivers State, Nigeria and its environs between November 2014 and February 2015.
Methodology: Thirty (30) Wistar albino rats were grouped into six (6) groups of five rats each. Group A served as the control and group B was administered an unblended zobo drink. Groups C – E were administered locally-produced zobo samples and group F was a National Agency for Food and Drug Administration and Control (NAFDAC)-branded zobo drink. A concentration of 200 mg/kg body weight of the samples was administered orally to the groups B – F for 21 days. Hepatic marker enzymes (ALT, AST and ALP), bilirubin (total and conjugated), albumin, total protein and renal indices were analyzed and compared.
Results: The results indicate that the activities of ALT, ALP, Albumin and Unconjugated bilirubin were significantly lower (P < 0.05), while Total protein and Total bilirubin levels were significantly higher (P < 0.05) than the control (Group A). AST and Conjugated bilirubin showed no significant difference (P > 0.05) in all the groups. The levels of Urea, Creatinine, Sodium (in group B), Potassium (K+), and Chloride (Cl-) were significantly higher (P < 0.05) than the control. The Sodium (Na+) level was significantly lower (P < 0.05) than the control in groups C, D and E.
Conclusion: The results of this study suggest that all the samples were not hepatotoxic. However, the aqueous extract of Zobo may have nephrotoxic and hepatotoxic effects if the concentration is increased over time.