Browsing by Author "Fadaka, Adewale Oluwaseun"
Now showing 1 - 18 of 18
Results Per Page
Sort Options
Item Anticancer and drug-sensitizing activities of gold nanoparticles synthesized from cyclopia genistoides (honeybush) extracts(MDPI, 2023) Sharma, Jyoti Rajan; Sibuyi, Nicole Remaliah Samantha; Fadaka, Adewale OluwaseunSynthesis of gold nanoparticles (AuNPs) using phytochemicals has become tremendously prominent in biomedical applications because of its enhanced bioactivity and biocompatibility. In this study, water extracts from the leaves of Cyclopia genistoides (C. genistoides), commonly known as honeybush (HB), were used to synthesize honeybush gold nanoparticles (HB-AuNPs). The HB water extracts (HBE) served as both reducing and capping agents in the synthesis of HB-AuNPs. The HB-AuNPs were characterized by UV–Vis spectrophotometry, dynamic light scattering (DLS), and transmission electron microscopy (TEM). The cytotoxicity and apoptotic effects of the HBE and HB-AuNPs, alone and in combination with doxorubicin (Dox), were examined against various human cell lines. Spherical-shaped HB-AuNPs with a hydrodynamic diameter range of 63 to 121 nm were produced.Item Attenuation of hyperglycemia-associated dyslipidemic, oxidative, cognitive, and inflammatory crises via modulation of neuronal ChEs/NF-κB/COX-2/NOx, and hepatorenal functional deficits by the Tridax procumbens extract(Elsevier, 2023) Hogan, Itam Ako; Fadaka, Adewale Oluwaseun; Kuo, Yu-ChengTridax procumbens (cotton buttons) is a flowering plant with a medicinal reputation for treating infections, wounds, diabetes, and liver and kidney diseases. The present research was conducted to evaluate the possible protective effects of the T. procumbens methanolic extract (TPME) on an experimentally induced type 2 diabetes rat model. Wistar rats with streptozotocin (STZ)-induced diabetes were randomly allocated into five groups of five animals each, viz., a normal glycemic group (I), diabetic rats receiving distilled water group (II), diabetic rats with 150 (III) and 300 mg/kg of TPME (IV) groups, and diabetic rats with 100 mg/kg metformin group (V). All treatments were administered for 21 consecutive days through oral gavage. Results: Administration of the T. procumbens extract to diabetic rats significantly restored alterations in levels of fasting blood glucose (FBG), body weight loss, serum and pancreatic insulin levels, and pancreatic histology. Furthermore, T. procumbens significantly attenuated the dyslipidemia (increased cholesterol, low-density lipoprotein-cholesterol (LDL-C), triglycerides, and high-density lipoprotein (HDL) in diabetic rats), serum biochemical alterations (alanine transaminase (ALT), aspartate transaminase (AST), alanine phosphatase (ALP), blood urea nitrogen (BUN), creatinine, uric acid, and urea) and full blood count distortion in rats with STZ-induced diabetes. The TPME also improved the antioxidant status as evidenced by increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and decreased malondialdehyde (MDA); and decreased levels of cholinesterases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)), and proinflammatory mediators including nuclear factor (NF)-κB, cyclooxygenase (COX)− 2, and nitrogen oxide (NOx) in the brain of rats with STZ-induced diabetes compared to rats with STZ-induced diabetes that received distilled water. However, TPME treatment failed to attenuate the elevated monoamine oxidases and decreased dopamine levels in the brain of rats with STZ-induced diabetes. Extract characterization by liquid chromatography mass spectrometry (LC-MS) identified isorhamnetin (retention time (RT)= 3.69 min, 8.8%), bixin (RT: 25.06 min, 4.72%), and lupeol (RT: 25.25 min, 2.88%) as the three most abundant bioactive compounds that could be responsible for the bioactivity of the plant. In conclusion, the TPME can be considered a promising alternative therapeutic option for managing diabetic complications owing to its antidiabetic, antihyperlipidemic, antioxidant, and anti-inflammatory effects in rats with STZ-prompted diabetes.Item Computational and preclinical prediction of the antimicrobial properties of an agent isolated from monodora myristica: A novel dna gyrase inhibitor(MDPI, 2023) Onikanni, Sunday Amos; Lawal, Bashir; Fadaka, Adewale Oluwaseun; Bakare, OluwafemiThe African nutmeg (Monodora myristica) is a medically useful plant. We, herein, aimed to critically examine whether bioactive compounds identified in the extracted oil of Monodora myristica could act as antimicrobial agents. To this end, we employed the Schrödinger platform as the computational tool to screen bioactive compounds identified in the oil of Monodora myristica. Our lead compound displayed the highest potency when compared with levofloxacin based on its binding affinity. The hit molecule was further subjected to an Absorption, Distribution, Metabolism, Excretion (ADME) prediction, and a Molecular Dynamics (MD) simulation was carried out on molecules with PubChem IDs 529885 and 175002 and on three standards (levofloxacin, cephalexin, and novobiocin). The MD analysis results demonstrated that two molecules are highly compact when compared to the native protein; thereby, this suggests that they could affect the protein on a structural and a functional level. The employed computational approach demonstrates that conformational changes occur in DNA gyrase after the binding of inhibitors; thereby, this resulted in structural and functional changes. These findings expand our knowledge on the inhibition of bacterial DNA gyrase and could pave the way for the discovery of new drugs for the treatment of multi-resistant bacterial infections.Item Computational insight of dexamethasone against potential targets of SARS-CoV-2(Taylor and Francis Group, 2022) Fadaka, Adewale Oluwaseun; Sibuyi, Nicole Remaliah Samantha; Madiehe, Abram MadimabeThe health sector has been on the race to find a potent therapy for coronavirus disease (COVID)-19, a diseases caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2. Repurposed anti-viral drugs have played a huge role in combating the virus, and most recently, dexamethasone (Dex) have shown its therapeutic activity in severe cases of COVID-19 patients. The study sought to provide insights on the anti-COVID-19 mechanism of Dex at both atomic and molecular level against SARSCoV-2 targets. Computational methods were employed to predict the binding affinity of Dex to SARSCoV-2 using the Schrodinger suite (v2020-2). The target molecules and ligand (Dex) were retrieved from PDB and PubChem, respectively. The selected targets were SARS-CoV-2 main protease (Mpro), and host secreted molecules glucocorticoid receptor, and Interleukin-6 (IL-6). Critical analyses such as Protein and ligand preparation, molecular docking, molecular dynamic (MD) simulations, and absorption, distribution, metabolism, excretion (ADME), and toxicity analyses were performed using the targets and the ligand as inputs.Item Development of Effective Therapeutic Molecule from Natural Sources against Coronavirus Protease(MDPI, 2021) Fadaka, Adewale Oluwaseun; Sibuyi, Nicole Remaliah Samantha; Martin, Darius Riziki; Klein, AshwilAbstract: The SARS-CoV-2 main protease (Mpro) is one of the molecular targets for drug design. Effective vaccines have been identified as a long-term solution but the rate at which they are being administered is slow in several countries, and mutations of SARS-CoV-2 could render them less effective. Moreover, remdesivir seems to work only with some types of COVID-19 patients. Hence, the continuous investigation of new treatments for this disease is pivotal. This study investigated the inhibitory role of natural products against SARS-CoV-2 Mpro as repurposable agents in the treatment of coronavirus disease 2019 (COVID-19). Through in silico approach, selected flavonoids were docked into the active site of Mpro. The free energies of the ligands complexed with Mpro were computationally estimated using the molecular mechanics-generalized Born surface area (MM/GBSA) method. In addition, the inhibition process of SARS-CoV-2 Mpro with these ligands was simulated at 100 ns in order to uncover the dynamic behavior and complex stability. The docking results showed that the selected flavonoids exhibited good poses in the binding domain of Mpro. The amino acid residues involved in the binding of the selected ligands correlated well with the residues involved with the mechanism-based inhibitor (N3) and the docking score of Quercetin-3-O- Neohesperidoside (−16.8 Kcal/mol) ranked efficiently with this inhibitor (−16.5 Kcal/mol). In addition, single-structure MM/GBSA rescoring method showed that Quercetin-3-O-Neohesperidoside (−87.60 Kcal/mol) is more energetically favored than N3 (−80.88 Kcal/mol) and other ligands (Myricetin 3-Rutinoside (−87.50 Kcal/mol), Quercetin 3-Rhamnoside (−80.17 Kcal/mol), Rutin (−58.98 Kcal/mol), and Myricitrin (−49.22 Kcal/mol). The molecular dynamics simulation (MDs) pinpointed the stability of these complexes over the course of 100 ns with reduced RMSD and RMSF. Based on the docking results and energy calculation, together with the RMSD of 1.98 ± 0.19 Å and RMSF of 1.00 ± 0.51 Å, Quercetin-3-O-Neohesperidoside is a better inhibitor of Mpro compared to N3 and other selected ligands and can be repurposed as a drug candidate for the treatment of COVID-19. In addition, this study demonstrated that in silico docking, free energy calculations, and MDs, respectively, are applicable to estimating the interaction, energetics, and dynamic behavior of molecular targets by natural products and can be used to direct the development of novel target function modulators.Item Diagnostic approaches of pneumonia for commercial-scale biomedical applications: An overview(Taylor & Francis, 2020) Bakare, Olalekan Olanrewaju; Fadaka, Adewale Oluwaseun; Klein, AshwilPneumonia remains the leading infectious cause of death among children under five years of age, and the elderly. Several biomarkers, which have been identified for its diagnosis lack specificity, as they could not differentiate viral from bacterial pathogens of the disease; these biomarkers also fail to establish a distinction between pneumonia and other associated diseases such as pulmonary tuberculosis and Human Immunodeficiency Virus (HIV). This review outlined the menace of pneumonia disease from the statistical prevalence, clinical and immunological view, challenges with the methods used in diagnosis, and more useful information about methods of diagnosis of pneumonia with their limitations as well. Additionally, the use of aptamers and antimicrobial peptides (AMPs) rather than antibodies to bind and recognize receptors for diagnostics, offers several advantages over other biomarkers shortcomings such as non-specificity.Item Dietary effects of antimicrobial peptides in therapeutics(Taylor & Francis, 2020-02-17) Bakare, Olalekan Olanrewaju; Fadaka, Adewale Oluwaseun; Klein, Ashwil; Pretorius, AshleyThe notable increase in drug-resistant infections and the failure of the most potent antibiotics to establish their curative effect without side effect have presented a serious need for the discovery of new therapeutic agent and the study of dietary implications on the mode of entry of these therapeutic agents in the human system. This review provides insight into the forms and modes of action, and roles of beneficial but limited and underutilized antimicrobial peptides for use in dietary formulations, with particular focus on the technologies employed for their discovery as well as their dietary efficacy. The wide spectrum of activities of these peptides will allow the opportunity to explore their benefits as dietary supplements and additives.Item Evaluation of terpenes rich hura crepitans extract on glucose regulation and diabetic complications in stz-induced diabetic rats(Elsevier Masson s.r.l., 2024-08-23) Lukman, Halimat Yusuf; Fadaka, Adewale Oluwaseun; Kuo, YuchengThe continual increase in global diabetic statistics portends decreased productivity and life spans, thus making it a disease of concern requiring more effective and safe therapeutic options. While several reports on antidiabetic plants, including Hura crepitans, are available, there is still a dearth of information on the holistic antidiabetic properties of H. crepitans and its associated complications. This study evaluated the antidiabetic potential of methanolic extract of Hura crepitans using in vitro, in vivo, and in silico approaches. The extract revealed a dosedependent in vitro effect, with a 47.97 % and 65.34 % decrease in the fasting blood sugar levels of streptozotocin (STZ) induced diabetic rats at 150 and 300 mg/kg BW, respectively. Likewise, the extract increased serum and pancreatic insulin levels, and significantly ameliorated neuronal oxidative stress and inflammation by reducing the expression levels of cholinesterase, NF-κB, and COX-2 in the brain of hyperglycemic rats. Serum dyslipidemia, liver, and kidney biomarker indices, and hematological alterations in diabetic rats were also significantly attenuated by the extract. Several constituents, mainly terpenes, were identified in the extract. To further predict the drug-likeness, pharmacokinetics, and binding properties of the compounds, in silico analysis was conducted. Ergosta-2,24-dien-26-oicacid,18-(acetyloxy)-5,6-epoxy-4, 22-dihydroxy-1-oxo-,delta.-lactone-4.beta., displayed the highest docking scores for acetylcholinesterase, butyrylcholinesterases, alpha-amylase, and nuclear factor-kB with values of − 12.4, − 10.9, − 10.3, and − 9.4 kcal/mol, while ergost-25-ene-6,12-dione,3,5-dihydroxy-, (3. beta.,5.alpha.) topped for cyclooxygenase-2 (-9.0 kcal/mol). The top-ranked compounds also presented significant oral drug-likeness, pharmacokinetics, and safety properties. Altogether, our data provide preclinical evidence of the potential of Hura crepitans in ameliorating diabetes and its associated complications.Item Functional prediction of candidate micrornas for CRC management using in silico approach(MDPI, 2019) Fadaka, Adewale Oluwaseun; Pretorius, Ashley; Klein, AshwilApproximately 30–50% of malignant growths can be prevented by avoiding risk factors and implementing evidence-based strategies. Colorectal cancer (CRC) accounted for the second most common cancer and the third most common cause of cancer death worldwide. This cancer subtype can be reduced by early detection and patients’ management. In this study, the functional roles of the identified microRNAs were determined using an in silico pipeline. Five microRNAs identified using an in silico approach alongside their seven target genes from our previous study were used as datasets in this study. Furthermore, the secondary structure and the thermodynamic energies of the microRNAs were revealed by Mfold algorithm. The triplex binding ability of the oligonucleotide with the target promoters were analyzed by Trident. Finally, evolutionary stage-specific somatic events and co-expression analysis of the target genes in CRC were analyzed by SEECancer and GeneMANIA plugin in Cytoscape. Four of the five microRNAs have the potential to form more than one secondary structure. The ranges of the observed/expected ratio of CpG dinucleotides of these genes range from 0.60 to 1.22.Item Gene expression alterations and molecular analysis of CHEK1 in solid tumors(MDPI, 2020) Fadaka, Adewale Oluwaseun; Bakare, Olalekan Olanrewaju; Sibuyi, Nicole Remaliah SamanthaAlterations in the Checkpoint kinase (CHEK1) gene, its regulation, and the possible clinical outcomes in human solid tumors have not been previously examined. Therefore, the present study was carried out to evaluate the expression of CHEK1 in solid tumors as well as the mechanism by which it can be regulated through non-coding RNAs. The expression of CHEK1 was investigated using Oncomine analysis. cBioPortal, Kaplan–Meier Plotter, and PrognoScan were performed to identify the prognostic roles of this gene in solid tumors. The copy number alteration, mutation, interactive analysis, and visualization of the altered networks were performed by cBioPortal. The molecular binding analysis was carried out by Schrodinger suite, PATCHDOCK, and discovery studio visualizer. The study demonstrated that the CHEK1 gene was differentially expressed in four different cancers, and that reduced CHEK1 mRNA expression is an unfavorable prognostic factor for patients with gastric and colorectal cancer. The molecular docking results showed that the CHEK1 gene can be regulated by microRNAs (miR-195-5p) due to the number of stable hydrogen atoms observed within the distance of 2.0 Å and the favorable amino acids (Ala221, Ile353, Ile365, Ile756, Val797, Val70, Val154, Ile159, Val347, Tyr804, Phe811, Tyr815, and Phe156) identified in the binding pocket of the argonaute protein.Item In silico identification of micrornas as candidate Colorectal cancer biomarkers(Sage Journals, 2019) Fadaka, Adewale OluwaseunThe involvement of microRNA in cancers plays a significant role in their pathogenesis. Specific expressions of these non-coding RNAs also serve as biomarkers for early colorectal cancer diagnosis, but their laboratory/molecular identification is challenging and expensive. The aim of this study was to identify potential microRNAs for colorectal cancer diagnosis using in silico approach. Sequence similarity search was employed to obtain the candidate microRNA from the datasets, and three target prediction software were employed to determine their target genes. To determine the involvement of these microRNAs in colorectal cancer, the microRNA gene list obtained was used alongside with colorectal cancer expressed genes from gbCRC and CoReCG databases for gene intersection analysis. The involvement of these genes in the cancer subtype was further strengthened with the DAVID databaseItem Inhibitory potential of repurposed drugs against the SARS-CoV-2 main protease: A computational-aided approach(Taylor and Francis, 2020) Fadaka, Adewale Oluwaseun; Aruleba, Raphael Taiwo; Sibuyi, Nicole Remaliah SamanthaThe exponential increase in cases and mortality of coronavirus disease (COVID-19) has called for a need to develop drugs to treat this infection. Using in silico and molecular docking approaches, this study investigated the inhibitory effects of Pradimicin A, Lamivudine, Plerixafor and Lopinavir against SARS-CoV-2 Mpro. ADME/Tox of the ligands, pharmacophore hypothesis of the co-crystalized ligand and the receptor, and docking studies were carried out on different modules of Schrodinger (2019-4) Maestro v12.2. Among the ligands subjected to ADME/Tox by QikProp, Lamivudine demonstrated drug-like physico-chemical properties. A total of five pharmacophore binding sites (A3, A4, R9, R10, and R11) were predicted from the co-crystalized ligand and the binding cavity of the SARS-CoV-2 Mpro. The docking result showed that Lopinavir and Lamivudine bind with a higher affinity and lower free energy than the standard ligand having a glide score of −9.2 kcal/mol and −5.3 kcal/mol, respectively.Item MicroRNA-based regulation of Aurora A kinase in breast cancer(Impact Journals, 2020) Sibuyi, Nicole Remaliah Samantha; Fadaka, Adewale Oluwaseun; Madiehe, Abram MadimabeThe involvement of non-coding RNAs (ncRNAs) in cellular physiology and disease pathogenesis is becoming increasingly relevant in recent years specifically in cancer research. Breast cancer (BC) has become a health concern and accounts for most of the cancer-related incidences and mortalities reported amongst females. In spite of the presence of promising tools for BC therapy, the mortality rate of metastatic BC cases is still high. Therefore, the genomic exploration of the BC subtype and the use of ncRNAs for possible regulation is pivotal. The expression and prognostic values of AURKA gene were assessed by Oncomine, GEPIA, KM-plotter, and bc-GenExMiner v4.4, respectively. Associated proteins and functional enrichment were evaluated by Cytoscape and DAVID databases. Additionally, molecular docking approach was employed to investigate the regulatory role of hsa-miR-32-3p assisted argonaute (AGO) protein of AURKA gene in BC. AURKA gene was highly expressed in patients with BC relative to normal counterpart and significantly correlated with poor survival. The docking result suggested that AURKA could be regulated by hsa-miR-32-3p as confirmed by the reported binding energy and specific interactions. The study gives some insights into role of AURKA and its regulation by microRNAs through AGO protein. It also provides exciting opportunities for cancer therapeutic intervention. © 2020 Fadaka et al.Item MicroRNAs as predictive biomarkers for diagnosis and prognosis of colorectal cancer using in silico approaches(University of the Western Cape, 2019) Fadaka, Adewale Oluwaseun; Klein, Ashwil; Pretorius, AshleyColorectal cancer (CRC) is referred to as cancers that arise in the colon or rectum. Rectal cancer is most often defined as cancers originating within 15 cm from the anal verge. The crude incidence of CRC in sub-Sahara African populations has been found to be 4.04/100,000 (4.38 for men and 3.69 for women). CRC stage correlates well with survival/cure rates with the majority of patients diagnosed with CRC presenting with advanced disease and a low survival/cure rate.Item Plant antimicrobial peptides (pamps): Features, applications, production, expression and challenges(MDPI, 2022) Bakare, Olalekan Olanrewaju; Gokul, Arun; Fadaka, Adewale OluwaseunThe quest for an extraordinary array of defense strategies is imperative to reduce the challenges of microbial attacks on plants and animals. Plant antimicrobial peptides (PAMPs) are a subset of antimicrobial peptides (AMPs). PAMPs elicit defense against microbial attacks and prevent drug resistance of pathogens given their wide spectrum activity, excellent structural stability, and diverse mechanism of action. This review aimed to identify the applications, features, production, expression, and challenges of PAMPs using its structure–activity relationship. The discovery techniques used to identify these peptides were also explored to provide insight into their significance in genomics, transcriptomics, proteomics, and their expression against disease-causing pathogens.Item Prospects of using gum Arabic silver nanoparticles in toothpaste to prevent dental caries(MDPI, 2023) Ahmed, Omnia Abdelmoneim Khidir; Sibuyi, Nicole Remaliah Samantha; Fadaka, Adewale OluwaseunThere is growing interest in the use of green synthesized silver nanoparticles (AgNPs) to control and prevent dental diseases. The incorporation of green synthesized AgNPs into dentifrices to reduce pathogenic oral microbes is motivated by their presumed biocompatibility and broad-spectrum antimicrobial activity. In the present study, gum arabic AgNPs (GA-AgNPs) were formulated into a toothpaste (TP) using a commercial TP at a non-active concentration, to produce GA-AgNPs_TP. The TP was selected after evaluating the antimicrobial activity of four commercial TPs 1-4 on selected oral microbes using agar disc diffusion and microdilution assays. The less active TP-1 was then used in the formulation of GA-AgNPs_TP-1; thereafter, the antimicrobial activity of GA-AgNPs_0.4g was compared to GA-AgNPs_TP-1. The cytotoxicity of GA-AgNPs_0.4g and GA-AgNPs_TP-1 was also assessed on the buccal mucosa fibroblast (BMF) cells using the MTT assay. The study demonstrated that antimicrobial activity of GA-AgNPs_0.4g was retained after being combined with a sub-lethal or inactive concentration of TP-1.Item Structural and molecular docking analytical studies of the predicted ligand binding sites of cadherin-1 in cancer prognostics(Dove Medical Press, 2020) Bakare, Olalekan Olanrewaju; Keyster, Marshall; Fadaka, Adewale OluwaseunSeveral studies have explored the design of antimicrobial peptides (AMPs) for the development of therapeutic and diagnostic molecules for the treatment and identification of pathogenic diseases as well as cancer. Human cadherin-1 protein has been identified to be involved in adhesion-mediated signalling pathways in normal cells and its loss through genetic and epigenetic alterations can result in an enhanced invasion and metastasis of malignancy in tumours. Therefore, the identification of cadherin during treatment of cancer can be used as prognostic biomarker to establish the responsiveness of patients to treatment regimen. Antimicrobial peptides (AMPs) offer several compensatory advantages in biomedical applications and have been used for treatment of diseases, dietary supplements and diagnosis of diseases. The aim of this research work was to use in silico approaches to analyse retrieved human cadherin-1 as prognostic targets in cancer treatments using modelled putative anticancer AMPs.Item Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2(SAGE, 2020) Sibuyi, Nicole Remaliah Samantha; Fadaka, Adewale Oluwaseun; Adewale, Olusola BolajiThe emergence of coronavirus disease 2019 (COVID-19) in December 2019 has resulted in over 20 million cases and 741,808 deaths globally, affecting more than 200 countries. COVID-19 was declared a pandemic on 11 March 2020 by the World Health Organization. The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). There is limited information on COVID-19, and treatment has so far focused on supportive care and use of repurposed drugs. COVID-19 can be transmitted via person-to-person contact through droplet spread. Some of the recommended precautionary measures to reduce the rate of disease spread include social distancing, good hygiene practices, and avoidance of crowded areas. These measures are effective because the droplets are heavy and can only travel approximately 1 meter in the air, settling quickly on fixed surfaces. Promising strategies to combat SARS-CoV-2 include discovery of therapeutic targets/drugs and vaccines. In this review, we summarize the epidemiology, pathophysiology, and diagnosis of COVID-19. We also address the mechanisms of action of approved repurposed drugs for therapeutic management of the disease.