Publications by authors named "Joseph O Adebayo"

9 Publications

  • Page 1 of 1

Structure-based virtual screening suggests inhibitors of 3-Chymotrypsin-Like Protease of SARS-CoV-2 from Vernonia amygdalina and Occinum gratissimum.

Comput Biol Med 2021 09 21;136:104671. Epub 2021 Jul 21.

Human Nutraceuticals and Bioinformatics Research Unit, Department of Biochemistry, Salem University, Nigeria.

Antiviral culinary plants are potential bioresources for preventive nutraceuticals and/or antiviral drugs in COVID-19. Structure-based virtual screening was undertaken to screen 173 compounds previously reported from Vernonia amygdalina and Occinum gratissimum for direct interaction with the active site of the 3-Chymotrypsin-Like Protease (3CL) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on docking scores and comparison with reference inhibitors, a hit-list of 10 top phytocompounds was defined, which also had strong interactions with the catalytic centre of 3CL from three related strains of coronavirus (SARS-CoV, MERS-CoV, HKU4). Among these, six compounds (neoandrographolide, vernolide, isorhamnetin, chicoric acid, luteolin, and myricetin) exhibited the highest binding tendencies to the equilibrated conformers of SARS-CoV-2 3CL in an in-depth docking analysis to 5 different representative conformations from the cluster analysis of the molecular dynamics simulation (MDS) trajectories of the protein. In silico drug-likeness analyses revealed two drug-like terpenoids viz: neoandrographolide and vernolide as promising inhibitors of SARS-CoV-2 3CL. These structures were accommodated within the substrate-binding pocket; and interacted with the catalytic dyad (Cys and His), the oxyanion loop (residues 138-145), and the S1/S2 sub-sites of the enzyme active site through the formation of an array of hydrogen bonds and hydrophobic interactions. Molecular dynamics simulation and binding free energy calculation revealed that the terpenoid-enzyme complexes exhibit strong interactions and structural stability. Therefore, these compounds may stabilize the conformation of the flexible oxyanion loop; and thereby interfere with the tetrahedral oxyanion intermediate formation during the proteolytic activity of the enzyme.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294106PMC
September 2021

Dual targeting of cytokine storm and viral replication in COVID-19 by plant-derived steroidal pregnanes: An in silico perspective.

Comput Biol Med 2021 07 18;134:104406. Epub 2021 Apr 18.

Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin, Nigeria.

The high morbidity and mortality rate of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection arises majorly from the Acute Respiratory Distress Syndrome and "cytokine storm" syndrome, which is sustained by an aberrant systemic inflammatory response and elevated pro-inflammatory cytokines. Thus, phytocompounds with broad-spectrum anti-inflammatory activity that target multiple SARS-CoV-2 proteins will enhance the development of effective drugs against the disease. In this study, an in-house library of 117 steroidal plant-derived pregnanes (PDPs) was docked in the active regions of human glucocorticoid receptors (hGRs) in a comparative molecular docking analysis. Based on the minimal binding energy and a comparative dexamethasone binding mode analysis, a list of top twenty ranked PDPs docked in the agonist conformation of hGR, with binding energies ranging between -9.8 and -11.2 kcal/mol, was obtained and analyzed for possible interactions with the human Janus kinases 1 and Interleukins-6 and SARS-CoV-2 3-chymotrypsin-like protease, Papain-like protease and RNA-dependent RNA polymerase. For each target protein, the top three ranked PDPs were selected. Eight PDPs (bregenin, hirundigenin, anhydroholantogenin, atratogenin A, atratogenin B, glaucogenin A, glaucogenin C and glaucogenin D) with high binding tendencies to the catalytic residues of multiple targets were identified. A high degree of structural stability was observed from the 100 ns molecular dynamics simulation analyses of glaucogenin C and hirundigenin complexes of hGR. The selected top-eight ranked PDPs demonstrated high druggable potentials and favourable in silico ADMET properties. Thus, the therapeutic potentials of glaucogenin C and hirundigenin can be explored for further in vitro and in vivo studies.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053224PMC
July 2021

Influence of gender on the distribution of type 2 diabetic complications at the obafemi awolowo teaching hospital, Ile-Ife, Nigeria.

Afr Health Sci 2020 Mar;20(1):294-307

Medicine Department, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria.

Background: Sex specific differences appear particularly relevant in the management of type 2 DM.

Objective: We determined gender specific differences in cardio-metabolic risk, microvascular and macrovascular complications in patients with type 2 diabetes.

Methods: Four hundred type 2 diabetes patients, males and females, matched for age and disease duration were recruited from the diabetes clinic. Relevant clinical and laboratory information were obtained or performed.

Results: 190(47.5%) were male and 210 (52.5%) were female respectively. The mean age of the study population was 60.6 + 9.93 years. Women had higher prevalence of hypertension (and obesity. Mean total cholesterol was significantly higher in women but men were more likely to achieve LDL treatment goals than women (69.5% vs 59.0%, p<0.05). More women (47.1% & 31.4%) reached glycaemic goals of <10mmol/l for 2HPP and HBA1c of <7.0%.There were no gender differences in the distribution of microvascular and macrovascular complications (p>0.05) but women were more likely to develop moderate and severe diabetic retinopathy (p= 0.027).

Conclusion: Women with T2DM had worse cardiometabolic risk profile with regards to hypertension, obesity and lipid goals. Men achieved therapeutic goals less frequently than did women in terms of glycaemia. Microvascular and macrovascular complications occurred commonly in both sexes.
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http://dx.doi.org/10.4314/ahs.v20i1.35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750067PMC
March 2020

Antioxidant defense system induced by cysteine-stabilized peptide fraction of aqueous extract of Morinda lucida leaf in selected tissues of Plasmodium berghei-infected mice.

J Integr Med 2017 09;15(5):388-397

Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin 24003, Nigeria.

Objective: This study evaluated the responses of some antioxidant parameters in selected tissues of Plasmodium berghei-infected mice treated with cysteine-stabilized peptide fraction (CSPF) of aqueous extract of Morinda lucida leaf.

Methods: Fifty-six mice were randomly divided into seven groups. Group A (normal control) was uninfected and received 5% dimethyl sulfoxide (DMSO). Mice in Groups B (negative control), C, D, E and F were inoculated with P. berghei NK65 and were administered with 5% DMSO and 15.63, 31.25, 61.5 and 125 mg/kg body weight of CSPF respectively. Group G animals, were also inoculated with P. berghei NK65, and received 20 mg/kg body weight of chloroquine. The administration lasted for three days, after which malondialdehyde (MDA) concentration and various antioxidant parameters in selected tissues of mice were determined on days 4 and 8 post-inoculation.

Results: The results revealed that MDA concentration was significantly increased (P < 0.05) in the tissues of the negative control and chloroquine-treated groups. The increased MDA concentration was reduced by CSPF in a dose-dependent manner, which was significant (P < 0.05) at higher doses. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and the concentration of reduced glutathione were significantly reduced (P < 0.05) in the tissues of the negative control animals compared to the normal controls. This observed reduction in the negative control animals was reverted in a dose-dependent manner in infected animals given CSPF, even to the range of the normal controls at highest dose, as did chloroquine.

Conclusion: The results suggest that CSPF of M. lucida leaf extract may induce the antioxidant defense system in vivo against Plasmodium species infection.
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http://dx.doi.org/10.1016/S2095-4964(17)60354-6DOI Listing
September 2017

Cysteine-stabilised peptide extract of Morinda lucida (Benth) leaf exhibits antimalarial activity and augments antioxidant defense system in P. berghei-infected mice.

J Ethnopharmacol 2017 Jul 20;207:118-128. Epub 2017 Jun 20.

Laboratorio de Malaria, Centro de Pesquisas Rene Rachou, FIOCRUZ, Belo Horizonte, MG, Brazil.

Ethnopharmacological Relevance: Cysteine-stabilised peptides (CSP) are majorly explored for their bioactivities with applications in medicine and agriculture. Morinda lucida leaf is used indigenously for the treatment of malaria; it also contains CSP but the role of CSP in the antimalarial activity of the leaf has not been evaluated.

Aim Of The Study: This study was therefore performed to evaluate the antimalarial activity of partially purified cysteine-stabilised peptide extract (PPCPE) of Morinda lucida leaf and its possible augmentation of the antioxidant systems of liver and erythrocytes in murine malaria.

Materials And Methods: PPCPE was prepared from Morinda lucida leaf. The activity of PPCPE was evaluated in vitro against Plasmodium falciparum W2 and its cytotoxicity against a BGM kidney cell line. PPCPE was also evaluated for its antimalarial activity and its effects on selected liver and erythrocyte antioxidant parameters in P. berghei NK65-infected mice.

Results: PPCPE was not active against P. falciparum W2 (IC: >50µg/ml) neither was it cytotoxic (MLD: >1000µg/ml). However, PPCPE was active against P. berghei NK65 in vivo, causing 51.52% reduction in parasitaemia at 31.25mg/Kg body weight on day 4 post-inoculation. PPCPE significantly reduced (P < 0.05) malondialdehyde concentrations in the liver and erythrocyte at higher doses compared to untreated controls. PPCPE increased glutathione concentration and activities of glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase in a dose-dependent manner, which was significant (P < 0.05) at higher doses compared to the untreated controls.

Conclusion: The results suggest that PPCPE may require bioactivation in vivo in order to exert its antimalarial effect and that PPCPE may augment the antioxidant defense system to alleviate the reactive oxygen species-mediated complications of malaria.
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http://dx.doi.org/10.1016/j.jep.2017.06.026DOI Listing
July 2017

Effects of aqueous extract of Hibiscus sabdariffa on renal Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in Wistar rats.

Zhong Xi Yi Jie He Xue Bao 2012 Sep;10(9):1049-55

Department of Physiology, University of Ilorin, Ilorin, Nigeria.

Objective: To investigate the effects of oral administration of aqueous extract of Hibiscus sabdariffa on renal Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in rats.

Methods: The 25 and 50 mg/(kg·d) of aqueous extracts of H. sabdariffa were respectively given to rats in the experimental groups for 28 d, and rats in the control group received an appropriate volume of distilled water as vehicle. Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in the kidney were assayed by spectrophotometric method.

Results: Administrations of 25 and 50 mg/(kg·d) of aqueous extract of H. sabdariffa significantly decreased the Ca(2+)-Mg(2+)-ATPase activity in the kidney of rats (P<0.05). However, the renal Na(+)-K(+)-ATPase activity of the experimental rats was not affected by either dose of the extract. And the plasma Na(+), K(+) and Ca(2+) levels of the experimental rats had no significant changes. Administration of either dose of the extract did not result in any significant changes in body and kidney weights, the concentrations of plasma albumin and total protein, and alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase activities. However, concentrations of creatinine and urea were significantly reduced by 50 mg/kg of the extract (P<0.05).

Conclusion: The present study indicates that oral administration of aqueous extract of H. sabdariffa may preserve the renal function despite a decreased renal Ca(2+)-Mg(2+)-ATPase activity.
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September 2012

Ethanolic extract of Clerodendrum violaceum Gürke leaves enhances kidney function in mouse model of malaria.

Indian J Exp Biol 2009 May;47(5):349-54

Department of Biochemistry, University of Ilorin, Ilorin, Kwara State, Nigeria.

Evaluation of the effects of daily oral administration of ethanolic extract of C. violaceum leaves (13 mg/kg body weight) for 5 days on some kidney function indices of uninfected and Plasmodium berghei-infected mice was done on days 3, 8 and 14 post-infection. The indices studied include serum urea and creatinine concentrations with the specific activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase in the kidney. Treatment of P. berghei-infected mice with ethanolic extract of C. violaceum leaves (13 mg/kg body weight) for 5 days was able to ameliorate significantly the alterations in the various parameters observed in infected untreated mice, comparing favourably with chloroquine treatment in most cases. Administration of extract to uninfected mice had no significant effect on both serum and kidney parameters compared to the uninfected control. The results suggest that the ethanolic extract of C. violaceum leaves does not adversely affect kidney function at the dose used in traditional medicine for the treatment of malaria but rather enhances it.
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May 2009

Testing of natural products and synthetic molecules aiming at new antimalarials.

Curr Drug Targets 2009 Mar;10(3):261-70

Malaria Laboratory, Institute René Rachou, FIOCRUZ, Belo Horizonte, MG, Brasil.

The search for new antimalarials, which in the past relied on animal models, is now usually performed with cultures of Plasmodium falciparum (PF) blood parasites by evaluation of parasite growth inhibition. Field isolates of PF human malaria parasite, parasite strains and clones, well characterized for their susceptibility to chloroquine and other standard antimalarials are available for the in vitro tests. The simplest method to evaluate parasite growth is the determination of parasitemias in Giemsa stained blood smears through light microscopy. Other methodologies have proven to be more precise and allow mass screening of new compounds against PF blood stages, such as: (i) measuring the incorporation of radioactive hypoxanthine by the parasites; (ii) indirect colorimetric assays in which specific parasite enzyme activities, and histidine-rich protein II (HRP2) production are measured with the help of monoclonal antibodies; (iii) the beta-haematin formation, and; (iv) assays using green fluorescent protein (GFP) in gene-expressing parasites. The advantages and disadvantages of the different in vitro screening methods, as well as the different in vivo models for antimalarial tests, are described in this review. Such tests can be used for the evaluation of medicinal plants, synthetic and hybrid molecules or drug combinations.
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http://dx.doi.org/10.2174/138945009787581203DOI Listing
March 2009

Effect of ethanolic extract of Khaya senegalensis on some biochemical parameters of rat kidney.

J Ethnopharmacol 2003 Sep;88(1):69-72

Department of Physiology and Biochemistry, Faculty of Health Sciences, University of Ilorin, Ilorin, Nigeria.

The effect of administration of ethanolic extract of Khaya senegalensis (2mg/kg body weight) on some biochemical parameters of rat kidney were investigated. Experimental animals were randomly divided into the control, those administered with the extract for 6 days and those administered with extract for 18 days, respectively. The prolonged administration of the extract resulted in significant reduction in the alkaline phosphatase activities of the kidney and its body weight ratio (P<0.05). In contrast, the same prolonged administration of the extract resulted in significant increase in the serum sodium ion concentration (P<0.05) while there was no significant difference in serum potassium ion concentration when compared to control (P>0.05). Administration of the extract for 6 days produced no significant difference from the control values in all the parameters investigated except in serum urea concentration which produced a significant increase (P<0.05). The available evidence in this study suggest that the ethanolic extract of Khaya senegalensis exerted more deleterious effect on the kidney when administered continuously over a prolonged period than a short one and this will adversely affect the functioning of the kidney.
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http://dx.doi.org/10.1016/s0378-8741(03)00193-4DOI Listing
September 2003
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