Effects of Momordica Charantia Silver Nanoparticles on the expressions of Genes Associated With Lipid Metabolism and Nephrotoxicity in Streptozotocin-Induced Rats

Hyperlipidemia and hyperglycemia have been implicated in diabetes mellitus (DM) leading to complications such as nephropathy. Medicinal plants like Mormodica charantia (MC) have been used in the treatment of DM over the years but little is known about their mechanisms of action. This study used biotechnology tools to investigate and compare the effects of M. charantia silver nanoparticles (MCSNPs) with M. charantia extract on expressions of genes linked with nephrotoxicity, lipid and glucose metabolisms using reverse-transcriptase polymerase chain reaction (RT-PCR) in streptozotocin-induced diabetic rats. The genes investigated include kidney injury molecule-1 (KIM-1), 3-hydroxyl, 3-methyl glutaryl_coA reductase (HMG-CoA reductase), peroxisome proliferator-activated receptor alpha and gamma (PPARα and PPARγ). Synthesis of MCSNPs was done using 1 mM concentration of aqueous silver nitrate solution at ratio 1:9 (v/v). Experimental rats were induced intraperitoneally with streptozotocin (65 mg/kg) and divided into six groups viz: diabetic control; normal control; silver nitrate (10 mg/kg); MCSNPs (50 mg/kg); Metformin (100 mg/kg) and M. charantia fraction (100 mg/kg). Sacrifice was done after 12 days of treatment and RT-PCR was then used to investigate gene expressions in liver and kidney tissues of the rats. The expression of HMG-CoA reductase gene was significantly upregulated (p<0.05) upon treatment with 50 mg/kg MCSNPs relative to the diabetic untreated group. M. charantia extracts and MCSNPs significantly upregulate (p<0.05) the expressions of PPAR-α and PPAR-γ compared to the diabetic control. Also, a significant (p<0.05) down-regulation of KIM-1 mRNA expression was observed in MCSNPs- treated group, relative to the diabetes untreated group. M. charantia silver nanoparticles could be a potent antidiabetic agent due to its potential to modulate genes associated with lipid metabolism and nephrotoxicity. Keywords: Medicinal plant; Diabetes Mellitus; Silver Nanoparticles; nephrotoxicity; gene expressio

Molecular modeling, dynamics simulation and characterization of human inositol hexakisphosphate kinase 1 (IP6K1) related to diabetes

Inositol hexakisphosphate kinase-1 (IP6K1) protein plays an important role in insulin signaling producing IP7 that inhibit the action of protein kinase B (Akt). Inhibition of IP6K1 has been proposed as a novel way to enhance insulin signaling. Characterization and binding interaction of IP6K1 is essential for rational anti-diabetic drug development targeting this protein. Computational tools were used to analyze the physicochemical characteristics of IP6K1. Homology modelling reliably predicts the tertiary structure of IP6K1. Derived three-dimensional models werethen used to predict the binding mode and interacting amino acid residues. MD simulation (30 ns) was employed to investigate the protein dynamics. The modeled IP6K1 exhibited secondary characteristics comprising of 63.3% helixes, 30.2% sheets and 13.4% turns with an aliphatic index of 65.83 and instability index 50.53 showing that the protein is relatively unstable without its appropriate environment. The extinction coefficient was 34560 while the grand average of hydropathicity was −0.724. Homology modelling was performed by SWISS-MODEL program and the proposed model was evaluated as reliable based on RAMPAGE’s Ramachandran plot, and ProSA analyses. RMSD, RMSF, Rg revealed that the protein attained stability around 20ns. This appeared to be the first attempt to portray molecular dynamic simulation of IP6K1 coupled with modeling and thorough characteristic analysis of the protein using parameters like Ramachandran plot, Chou and Fasman Secondary Structure prediction and Protparam. Studies like protein engineering, structure and function as well as activity analysis are suggested. Our computational studies reavealed the binding pocket and critical amino acid residues that can be exploited in the design of inhibitors of IP6K1 as antidiabetic drugs.Keywords: Insulin signaling, physicochemical characteristics, homology modelling, diabete

Isolation and Elucidation of 15-Acetylguanacone from Soursop (Annona muricata Linn) Fruit and Molecular Docking Experiments

Annona muricata (Soursop) has attracted attention due to its content of annonaceous acetogenins, a large family of naturally occurring polyketides isolated from various species of the genus Annonaceae. The ethyl acetate fraction of Annona muricata was subjected to standard isolation protocol-gradient and isocratic silica gel column chromatography- to obtain three waxy and whitish amorphous compounds, 002/A1, 002/A2 and 002/C. The structure of compound 200/A2 was elucidated using 1H-NMR spectroscopy, infrared spectroscopy and electron impact (EI+) mass spectroscopy. The molecular weight of 200/A2 was determined as 662 by EI-MS ([M+H]+ : m/z = 662.1) leading to the molecular formula C39H66O8 as obtained using high resolution MS. The existence of an α, β-unsaturated γ-lactone moiety, non-hydroxylated at the C-4 position, was suggested by an IR carbonyl absorption at 1735.9 cm-1 and 1662.7 cm-1; the IR also gave signal for hydroxyl group at 3339.0 cm-1. The presence of a characteristic vinyl proton δ 7.24 (H-35, d), which is characteristic for α, β- unsaturated γ-lactone was confirmed by the 1H-NMR spectrum. The compound was thus elucidated to be 15-acetyl guanacone, an acetogenin. This acetogenin has not been reported in Annona muricata previously. The compound was subsequently subjected to molecular docking experiments which revealed that it targets and binds to vascular endothelial growth factor 2, VEGF2 (-8.5kcal/mole) and α1 β2 integrin (-6.8kcal/mole), This thus suggests that 15-acetyl guanacone prevents metastasis and invasion by cancer cells, and ultimately initiates apoptosis.Key words: VEGF2; Integrin; Cancer; Acetogenins; Apoptosis; Soursop

Safety of yam-derived (Dioscorea rotundata) foodstuffs—chips, flakes and flour: Effect of processing and post-processing conditions

The production of yam-derived (Dioscorea rotundata) foodstuffs is mainly performed by small and medium scale processors that employ old traditional methods. This can lead to differences in quality from processor to processor, and from location to location, with consequent safety concerns. As such, the effects of processing and post-processing phases (i.e., storage, transport, etc.) on the safety of some yam-derived foodstuffs—namely chips, flakes, and flour—has been evaluated, with a focus on bacterial and fungal contamination, aflatoxins, pesticides, and heavy metals (Pb, Ni, Cd and Hg). Yams harvested and processed in Nigeria were screened, being that the country is the largest producer of the tuber, with 70–75% of the world production. Results highlighted no presence of pesticides, however, many samples showed high levels of bacterial and fungal contamination, together with heavy metal concentrations above the recommended safety levels. No trend was observed between the items considered; it was noticed, however, that samples purchased from the markets showed higher contamination levels than those freshly produced, especially regarding bacterial and aflatoxins presence. The processing stage was identified as the most critical, especially drying. Nonetheless, post-processing steps such as storage and handling at the point of sale also contributed for chemical contamination, such as aflatoxin and heavy metals. The results suggested that both the processing and post-processing phases have an impact on the safety of yam chips, flakes, and flour

Computer-aided identification of bioactive compounds from Gongronema latifolium leaf with therapeutic potential against GSK3β, PTB1B and SGLT2

The modulation of certain molecular targets via small-molecule ligands has been regarded as a promising approach for the treatment and management of diabetes-related complications. Notable among these targets are the Glycogen synthase kinase (GSK3β), protein tyrosine phosphatase 1B (PTB1B), and sodium-glucose cotransporter 2 (SGLT2), whose inhibitions have been associated with high prognostic patients with diabetic related complications. However, inhibitors capable of exerting co-modulating effects on the three aforementioned proteins are lacking. Therefore, research aimed at the development of small molecule inhibitors capable of co-targeting these proteins remains unfaltering. Consequently, this study investigated the inhibitory potentials of Gongronema latifolium leaf's compounds against these proteins. Molecular docking was employed to screen 134 compounds against these targets; this gave rise to the identification of ten lead compounds (rutin, epigallocatechin-3-gallate, silymarin, hyperoside, luteolin, baicalin, rosmarinic acid, naringin, butein, and isoorientin) based on their high binding affinities. Subsequently, the toxicity profiles of the compounds were assessed while their bioactivities against the proteins were predicted using 2D quantitative structure-activity relationship (QSAR) models. Furthermore, density functional theory (DFT) calculations were employed to study the reactivity and stability of the aforementioned compounds. Ultimately, toxicity assessment revealed epigallocatechin-3-gallate and butein as the compounds with minimal toxicity, while DFT calculations revealed baicalin, rosmarinic acid, and butein as the most reactive among the lead compounds. Conclusively, this study provides insight into the discovery of phytocompounds with promising inhibitory potential that could facilitate the development of regimens for diabetes management after further in vitro and in vivo studies

Knowledge of prostate cancer and screening practices among men attending urology clinics in tertiary and private health centers in southern Nigeria

Prostate cancer, a disease of public health importance is the most diagnosed solid tumour in men and second leading cause of mortalities in developed and most developed countries. The aim of this study was to assess the level of knowledge of prostate cancer and screening practices among men attending urology clinics of a tertiary and private based health centers in southern Nigeria. This is a descriptive cross-sectional study and demographic and anthropometric data were collected using well-structured self-administered questionnaires from consented men. A total of three hundred and fifty men participated in this study, 150 were diagnosed of prostate (Mean age 59.4±0.85), 100 were diagnosed with benign prostatic hyperplasia (Mean age 57.8±0.76) and 100 were apparently healthy men used as controls (Mean age 53.5±0.53). Majority of the respondents (58.3%) diagnosed with prostate cancer had knowledge of the disease. A low level of screening practices of prostate cancer (34.1%) was observed among respondents. The study showed statistically significant association between the level of education and knowledge of the disease in all the study groups (P<0.05). Increased education will improve awareness of the disease and positive response to screening which will aid early detection and diagnosis. Key words: prostate cancer; benign prostatic hyperplasia; screening

Saponins in Cancer Treatment: Current Progress and Future Prospects

Saponins are steroidal or triterpenoid glycoside that is distinguished by the soap-forming nature. Different saponins have been characterized and purified and are gaining attention in cancer chemotherapy. Saponins possess high structural diversity, which is linked to the anticancer activities. Several studies have reported the role of saponins in cancer and the mechanism of actions, including cell-cycle arrest, antioxidant activity, cellular invasion inhibition, induction of apoptosis and autophagy. Despite the extensive research and significant anticancer effects of saponins, there are currently no known FDA-approved saponin-based anticancer drugs. This can be attributed to a number of limitations, including toxicities and drug-likeness properties. Recent studies have explored options such as combination therapy and drug delivery systems to ensure increased efficacy and decreased toxicity in saponin. This review discusses the current knowledge on different saponins, their anticancer activity and mechanisms of action, as well as promising research within the last two decades and recommendations for future studies

DESIGN, SYNTHESIS, DOCKING, ANTITUMOR SCREENING, AND ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION PREDICTION OF NEW HESPERDIN DERIVATIVE

Objective: Hesperidin (HSP) is a pharmacologically active organic compound found in citrus fruits and peppermint. We synthesized a new HSP derivative by reacting it with 5-Amino-1,3,4-thiadiazole-2-thiol in acetic acid. Methods: This compound was characterized by Fourier-transform infrared, proton nuclear magnetic resonance, and electron impact mass spectra. A molecular docking study explores the predicted binding of the compound and its possible mode of action. Bioavailability, site of absorption, drug mimic, and topological polar surface was predicted using absorption, distribution, metabolism, and excretion (ADME) studies. Results: The docking study predicts that the new compound binds to the active sites of Aurora-B and the MST3 pocket and has good ADME properties. Moreover, the thiazole ring and the presence of the electron releasing groups and hydrogen bond interaction with amino acid residues within the active sites play an important role in enhancing the antioxidant activity. Conclusion: In the present study, a new HSP derivative has been synthesized and characterized successfully and a theoretically promising antioxidant and anticytotoxic active agent introduced. We have shown the detailed binding analysis of 1,3,4-thiadiazol and hydrogen bonds with the inhibitor binding cavity of Aurora B and MST3. This could provide the development of some effective compounds against different diseases