Antiplasmodial flavonoid from young twigs and leaves of Caesalpinia bonduc (Linn) Roxb

Young twigs and leaves of Caesalpinia bonduc (Linn) Roxb is used in the Southwestern part of Nigeria, as an antimalarial medicinal decoction together with other medicinal plant. In order to discover new antimalaria drug or drug lead and also to verify the traditional use of C. bonduc in this area, the in vitro antiplasmodial activity of crude extract, solvent fractions and compounds isolated from C. bonduc were investigated. In vitro antiplasmodial evaluation was carried out using chloroquine sensitive strain of Plasmodium falciparum FCR-3 and selective toxicity determination was investigated using sensitivity study on Mouse mammary tumor FM3A cells as a host model. Ethyl acetate and petroleum ether soluble solvent fractions of C. bonduc showed antiplasmodial activity with EC50 values of 16 and 18 μg/mL and selectivity index (SI) of 0.69 and 0.29 respectively. Bioassay guided fractionation of C. bonduc led to the isolation of seven flavonoids, 7-hydroxy-4'-methoxy-3,11- dehydrohomoisoflavanone (1), 4,4'-dihydroxy-2'-methoxy-chalcone (2), 7,3'-dihydroxy-3,11-dehydrohomoisoflavanone (3), Luteolin (4), quercetin-3-methyl ether (5), Kaempferol-3-O-b-D-xylopyranoside (6)and Kaempferol-3-O-a-L-rhamnopyranosyl-(1®2)-B-D-xylopyranoside (7). Structures of compounds 1 to 7 were elucidated by spectroscopic methods. Compound 2 exhibited moderate antiplasmodial activity with EC50 and SI values of 33 μM and 0.33 respectively while compounds 1, 3 to 7 showed insignificant antiplasmodial activity. The investigation revealed that the moderate antiplasmodial activity exhibited by the solvent fractions of C. bonduc might be mediated by 4,4'-dihydroxy-2'-methoxy-chalcone

Antiplasmodial activity of quinine-zinc complex and chloroquine: A comparative in vitro assessment

The evolving and complicating drug resistance exhibited by strains of Plasmodium falciparum to existing antimalarials like chloroquine and quinine (which are relatively more affordable than recent drugs) and advances in metal-drug complex research instigated this work. The antiplasmodial activity of the Quinine-Zinc complex (QZ) synthesized by a modification of the method of Singla and Wadhwa was assessed relative to that of Chloroquine diphosphate (C) in vitro. Measurement of antiplasmodial activity was carried out based on the inhibition of parasite growth measured by the inhibition of schizont formation in freshly collected infected blood samples from malaria patients. A comparative analysis of the antiplasmodial activity of QZ against C showed that its antiplasmodial activity was significantly better than that of C (p < 0.05). The result of this study suggests that the QZ could have a better therapeutic activity against malaria than C

Potential Anti-Cancer Flavonoids Isolated From Caesalpinia bonduc Young Twigs and Leaves: Molecular Docking and In Silico Studies

Tyrosine kinase (TK), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) are important cancer therapeutic target proteins. Based on reported anti-cancer and cytotoxic activities of Caesalpinia bonduc, this study isolated phytochemicals from young twigs and leaves of C bonduc and identified the interaction between them and cancer target proteins (TK, VEGF, and MMP) in silico. AutoDock Vina, iGEMDOCK, and analysis of pharmacokinetic and pharmacodynamic properties of the isolated bioactives as therapeutic molecules were performed. Seven phytochemicals (7-hydroxy-4′-methoxy-3,11-dehydrohomoisoflavanone, 4,4′-dihydroxy-2’-methoxychalcone, 7,4′-dihydroxy-3,11-dehydrohomoisoflavanone, luteolin, quercetin-3-methyl, kaempferol-3-O-β-d-xylopyranoside and kaempferol- 3-O-α-l-rhamnopyranosyl-(1 → 2)-β-D-xylopyranoside) were isolated. Molecular docking analysis showed that the phytochemicals displayed strong interactions with the proteins compared with their respective drug inhibitors. Pharmacokinetic and pharmacodynamic properties of the compounds were promising suggesting that they can be developed as putative lead compounds for developing new anti-cancer drugs

Antioxidant and DPPH-Scavenging Activities of Compounds and Ethanolic Extract of the Leaf and Twigs of Caesalpinia bonduc L. Roxb.

Antioxidant effects of ethanolic extract of Caesalpinia bonduc and its isolated bioactive compounds were evaluated in vitro. The compounds included two new cassanediterpenes, 1α,7α-diacetoxy-5α,6β-dihydroxyl-cass-14(15)-epoxy-16,12-olide (1)and 12α-ethoxyl-1α,14β-diacetoxy-2α,5α-dihydroxyl cass-13(15)-en-16,12-olide(2); and others, bonducellin (3), 7,4’-dihydroxy-3,11-dehydrohomoisoflavanone (4), daucosterol (5), luteolin (6), quercetin-3-methyl ether (7) and kaempferol-3-O-α-L-rhamnopyranosyl-(1Ç2)-β-D-xylopyranoside (8). The antioxidant properties of the extract and compounds were assessed by the measurement of the total phenolic content, ascorbic acid content, total antioxidant capacity and 1-1-diphenyl-2-picryl hydrazyl (DPPH) and hydrogen peroxide radicals scavenging activities.Compounds 3, 6, 7 and ethanolic extract had DPPH scavenging activities with IC50 values of 186, 75, 17 and 102 μg/ml respectively when compared to vitamin C with 15 μg/ml. On the other hand, no significant results were obtained for hydrogen peroxide radical. In addition, compound 7 has the highest phenolic content of 0.81±0.01 mg/ml of gallic acid equivalent while compound 8 showed the highest total antioxidant capacity with 254.31±3.54 and 199.82±2.78 μg/ml gallic and ascorbic acid equivalent respectively. Compound 4 and ethanolic extract showed a high ascorbic acid content of 2.26±0.01 and 6.78±0.03 mg/ml respectively.The results obtained showed the antioxidant activity of the ethanolic extract of C. bonduc and deduced that this activity was mediated by its isolated bioactive compounds

The Anopheles gambiae Insecticidal Targets Made Bare by In-silica Analysis

seveml wot·ks had attempted to use genomics to explain the mode of mosquito t·esistance and pt·edict dmg tat·get. The use of insecticides in val'ious ways has been the majm· malal'ia vectot· conti'Ol stmtegy being deployed lately, mostly pyt·ethi'Oid, the majm· t·ecommended compound class fot· IRS, ITNs and LLITNs. Resistance to dmgs and insecticides has continually obstmcted vectm·/malal'ia contt·ol stntegies. The advet·t effect is so enonnous in the Sub-Sahamn Afl'ican; its socioeconomic impact is unquantifiable in evet·y measm·e. Thus, the quick necessity fm· the development and elucidation of potent, cheap and efficient new potential insecticidal tat·gets, especially those in the class pyt·ethi'Oid fm· the malal'ia vectot·, A. gambiae. In this wm·k, an updated Anopheles gambiae biochemical metabolic netwm·k (AnoCyc vel'l.O), othet·wise known as pathway genome database (PGDB) was extmcted, the database was t·econstt·ucted by developing a computational gmph model in an appi'Oach that modeled the metabolic netwot·k of the m·ganism as a bipat·tite gmph, deployed the concept of choke point, load point and t·eaction without deviation to detet·mine the essential enzymatic t·eactions in the netwm·ks. Each potential dmg tat·get to theit· coiTesponding gene/pi'Otein and such encoding pi'Otein sequences wet·e extmcted. (PDB) was blasted fot· genes that have stmctm·e m· homologue of >= 30 sequence identity. Finally, we deployed Ovet·ton and Bation Scm·e (OB-Scm·e) and Pat·Ct·ys pt·ediction to mnk pi'Oteins by theit' likely success in ct·ystallization. 61 potential insecticidal candidate tat·gets was made bat·e, one clinically validated insecticidal tat·get and othet·s with biological evidence in the litemtnt·e. Seven of these tat·gets ideally stand out and have no homology with othet· vetiebmtes. These in depth dissection of the biochemical metabolic netwm·ks of the Anopheles effectively identified the ideal gene pi'Oducts and specifically extmct essential enzymes as new potential insecticidal tat·get against A. gambiae

Effects of combinations of ethanolic extracts of Blighia sapida and Xylopia aethiopica on progesterone, estradiol and lipid profile levels in pregnant rabbits

The effects of ethanolic extracts of Xylopia aethiopica fruits and Blighia sapida roots, used by some rural dwellers in western part of Nigeria for arbortifacient purposes, were investigated using pregnant rabbits. A combination of X. aethiopica and B. sapida in a ratio 1:1 at concentrations of 10.0 mg/ kg body weight (group B) and 50.0 mg/ kg body weight (group C), and X. aethiopica alone at 50.0 mg/kg of body weight (group D) were administered by gastric intubations for a period of 14 days from the 12th to 25th day of gestation after which they were fasted for 18 h. Serum levels of reproductive hormones (progesterone and estradiol) and lipids (triglycerides, total cholesterol, LDL-cholesterol and HDLcholesterol) were determined at the end of the treatment. Results showed significant reductions (p < 0.05) in progesterone and estradiol levels, significant elevations of triglycerides (p < 0.05) and no statistically significant differences (p < 0.05) in the levels of total cholesterol in all the treated groups compared with the control (group A). There was a statistically significant reduction (p < 0.05) in the levels of HDL-cholesterol in Group B, a significant increase in group C and no significant reduction in group D compared with the control (group A). The levels of LDL-cholesterol in all the treated groups did not differ significantly (p < 0.05) from the control (group A). The results suggest that ethanolic extracts of X. aethiopica alone or in combination with B. sapida may actually lead to termination of pregnancy due to reduction of progesterone and estradiol. The results also suggest that there is increased risk of hypertriglyceridemia in the users of these plants but this may not predispose them to arteriosclerosis because of the insignificant differences in the levels of LDL-cholesterol in all the treated groups compared with the control

Effects of combinations of ethanolic extracts of Blighia sapida and Xylopia aethiopica on progesterone, estradiol and lipid profile levels in pregnant rabbits

The effects of ethanolic extracts of Xylopia aethiopica fruits and Blighia sapida roots, used by some rural dwellers in western part of Nigeria for arbortifacient purposes, were investigated using pregnant rabbits. A combination of X. aethiopica and B. sapida in a ratio 1:1 at concentrations of 10.0 mg/ kg body weight (group B) and 50.0 mg/ kg body weight (group C), and X. aethiopica alone at 50.0 mg/kg of body weight (group D) were administered by gastric intubations for a period of 14 days from the 12th to 25th day of gestation after which they were fasted for 18 h. Serum levels of reproductive hormones (progesterone and estradiol) and lipids (triglycerides, total cholesterol, LDL-cholesterol and HDL- cholesterol) were determined at the end of the treatment. Results showed significant reductions (p < 0.05) in progesterone and estradiol levels, significant elevations of triglycerides (p < 0.05) and no statistically significant differences (p < 0.05) in the levels of total cholesterol in all the treated groups compared with the control (group A). There was a statistically significant reduction (p < 0.05) in the levels of HDL-cholesterol in Group B, a significant increase in group C and no significant reduction in group D compared with the control (group A). The levels of LDL-cholesterol in all the treated groups did not differ significantly (p < 0.05) from the control (group A). The results suggest that ethanolic extracts of X. aethiopica alone or in combination with B. sapida may actually lead to termination of pregnancy due to reduction of progesterone and estradiol. The results also suggest that there is increased risk of hypertriglyceridemia in the users of these plants but this may not predispose them to arteriosclerosis because of the insignificant differences in the levels of LDL-cholesterol in all the treated groups compared with the control

Abstract B048: Androgen metabolism and incidence of prostate cancer in Nigeria

The risk of prostate cancer among blacks, especially of Nigerian descent, is higher than other races. This could be attributed to biologic and genetic variability. The role of androgen metabolism in prognosis of prostate cancer has been delineated and reported. One of the enzymes involved in androgen metabolism is CYP3A4, which has not been studied in Nigerian men afflicted with prostate cancer. Racial differences in this functional gene may contribute to variations in incidence of prostate cancer across ethnic divides. Therefore, identifying a diagnostic and prognostic biomarker such as CYP3A4 polymorphism for prostate cancer in black men will improve the treatment and management of the disease. In this study, we investigated the genotypes of CYP3A4 of prostate cancer patients from Nigeria for possible correlation to the high incidence of the disease in Nigerian men. The results obtained showed a preponderance of the GG genotypes, which indicates a possible correlation between this genotype of CYP3A4 and higher risk of prostate cancer among Nigerian men

Hepatoprotective Potential and Histological Studies of Effects of Celosia Argentea L. on Paracetamol-Induced Liver Damage

Celosia argentea L. is a common vegetable known to possess anti-oxidative and other therapeutic properties. This study evaluates the hepatoprotective activities and histological effects of aqueous extract of Celosia argentea L. on acetaminophen-induced liver damage in rats, compared to the effects of a standard drug –silymarin. Twenty-five male rats were used in this study. These were divided into five groups of five animals each. Animals in group 1 were given 1ml/kg body weight (b.w)distilled water (control [C]), group 2 were given 100mg/kg b.w silymarin for 4 days plus acetaminophen for 3 days [SL], groups 3 and 4 were given 250 and 500mg/kg b.w aqueous extract of C. argentea for 4 days plus acetaminophen for 3 days (CA1 and CA2, respectively) and group 5 were given 1 ml/kg b.w. distilled water for 4 days and 1g/kg b.w acetaminophen (PCM) for 3 days. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin activities were assessed on day 8, values of mean and standard error were compared at significance level of p 0.05). Mean values in control group were similar to CA2 but significantly lower than PCM and CA1. Total bilirubin was higher but not significantly different compared to C group, suggesting a lack of effect on total bilirubin. C. argentea ameliorates and protects against acetaminophen-induced liver damage in rats, with a comparable effect with silymarin at a dose of 500mg/kg b.w. A regular consumption of the vegetable can play a role in sustaining health and can be used in place of long term therapy in individuals with compromised liver or actively exposed to chemotherapeutic drugs with adverse effects on liver

Machine learning approaches to genome-wide association studies

Genome-wide Association Studies (GWAS) are conducted to identify single nucleotide polymorphisms (variants) associated with a phenotype within a specific population. These variants associated with diseases have a complex molecular aetiology with which they cause the disease phenotype. The genotyping data generated from subjects of study is of high dimensionality, which is a challenge. The problem is that the dataset has a large number of features and a relatively smaller sample size. However, statistical testing is the standard approach being applied to identify these variants that influence the phenotype of interest. The wide applications and abilities of Machine Learning (ML) algorithms promise to understand the effects of these variants better. The aim of this work is to discuss the applications and future trends of ML algorithms in GWAS towards understanding the effects of population genetic variant. It was discovered that algorithms such as classification, regression, ensemble, and neural networks have been applied to GWAS for which this work has further discussed comprehensively including their application areas. The ML algorithms have been applied to the identification of significant single nucleotide polymorphisms (SNP), disease risk assessment & prediction, detection of epistatic non-linear interaction, and integrated with other omics sets. This comprehensive review has highlighted these areas of application and sheds light on the promise of innovating machine learning algorithms into the computational and statistical pipeline of genome-wide association studies. This will be beneficial for better understanding of how variants are affected by disease biology and how the same variants can influence risk by developing a particular phenotype for favourable natural selection