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Introduction
I am presently a Japan Society for the Promotion of Science (JSPS) research fellow at the Structure Based Drug Discovery Group, National Institute for Advanced Industrial Science and Technology, Tsukuba, Japan, where I am working on the gene cloning, expression and crystallisation of AV related trypanosomal proteins
Current institution
Ahmadu Bello University | ABU
Department of Biochemistry
Current position
Senior Lecturer
Skills and Expertise
Education
Jan 2011 - Apr 2014
University of KwaZulu-Natal
Biochemistry
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University of KwaZulu-Natal
King Abdullah University of Science and Technology
Kaduna State University
University of Medical Sciences, Ondo
Tikrit University
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University of KwaZulu-Natal
Lagos State University
Ahmadu Bello University
Ekiti State University, Ado Ekiti
Federal University of Technology, Akure
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Projects (8)
Extensive and intensive research in the use of phytochemicals, nutraceuticals and sweeteners in the management of type 2 diabetes, oxidative stress and related diseases; elucidating their therapeutic potentials and underlying mechanisms of action
Discovery of potent antidiabetic nutraceuticals and supplements with minimal side effects.
Hepatoprotective and antioxidative properties of ethanolic extract of root of Leea macrophylla in carbon tetrachloride (CCl4) induced liver damage in rats
The major goal of the project is to explore the effectiveness of leea macrophylla in ameliorating the chemical induced liver toxicity
Search for plant-derived antidiabetic compounds/nutraceuticals, mode of actions and molecular mechanisms behind the anti-diabetic actions of various African medicinal plants/functional food.
Our overarching goal focuses on screening and isolation of potent ingredients/nutraceuticals with antidiabetic potentials from vast wealth of plants located in African region using modern spectroscopic techniques. In addition, we are interested in elucidating the possible mode of actions of extracts, compounds or nutraceuticals derived from the plants using various in vitro and in vivo models. Presently, we focus on the in silico computer simulation and improving bioavailability of spice-derived nutraceuticals as possible antidiabetic agents.
Research
Research Items (130)
Stigmasterol has been reported to possess antitrypanosomal activity using in vitro model but information on the in vivo antitrypanosomal effects which is necessary in drug development process has not been evaluated. Hence, the present study investigates the in vivo effects of stigmasterol against T. congolense in addition to its inhibitory effects of trypanosomal sialidase. Stigmasterol, at 100 mg/kg BW, did not significantly (p > 0.05) reduce the progression of T. congolense infection in animals but a 200 mg/kg BW stigmasterol treatment significantly (p < 0.05) reduced the parasitemia, although, it did not completely eliminate the parasite from the bloodstream of infected animals. However, the stigmasterol treatments significantly (p < 0.05) ameliorated the T. congolense induced anemia as well as hepatic and renal damages. Furthermore, the T. congolense-associated increase in free serum sialic acid with a corresponding decrease in membrane bound sialic acid were prevented, though insignificantly (p > 0.05), by the 200 mg/kg BW treatment. Subsequently, in vitro enzyme kinetic studies revealed that stigmasterol is an uncompetitive inhibitor of a partially purified bloodstream T. congolense sialidase with an inhibition binding constant of 356.59 μM. Using molecular docking studies, stigmasterol formed a single hydrogen bonding interaction with a major residue (D⁶³) at the catalytic domain of T. rangeli sialidase with a predicted binding free energy of −24.012 kcal/mol. We concluded that stigmasterol could retard the proliferation and the major pathological features of T. congolense infection whilst the anemia amelioration was mediated via inhibition of sialidase.
Klebsiella pneumoniae is one of the perturbing multidrug resistant (MDR) and ESKAPE pathogens contributing to the mounting morbidity, mortality and extended rate of hospitalization. Its virulence, often regulated by quorum sensing (QS) reinforces the need to explore alternative and prospective antivirulence agents, relatively from plants secondary metabolites. Computer aided drug discovery using molecular modelling techniques offers advantage to investigate prospective drugs to combat MDR pathogens. Thus, this study employed virtual screening of selected terpenes and flavonoids from medicinal plants to interrupt the QS associated SdiA protein in K. pneumoniae to attenuate its virulence. 4LFU was used as a template to model the structure of SdiA. ProCheck, Verify3D, Ramachandran plot scores, and ProSA-Web all attested to the model’s good quality. Since SdiA protein in K. pneumoniae leads to the expression of virulence, 31 prospective bioactive compounds were docked for antagonistic potential. The stability of the protein-ligand complex, atomic motions and inter-atomic interactions were further investigated through molecular dynamics simulations (MDS) at 100 ns production runs. The binding free energy was estimated using the molecular mechanics/ poisson-boltzmann surface area (MM/PB-SA). Furthermore, the drug-likeness properties of the studied compounds were validated. Docking studies showed phytol possesses the highest binding affinity (-9.205 kcal/mol) while glycitein had -9.752 kcal/mol highest docking score. The MDS of the protein in complex with the best-docked compounds revealed phytol with the highest binding energy of -44.2625 kcal/mol, a low root-mean-square deviation (RMSD) value of 1.54 Å and root-mean-square fluctuation (RMSF) score of 1.78 Å. Analysis of the drug-likeness properties prediction and bioavailability of these compounds revealed their conformed activity to lipinski’s rules with bioavailability scores of 0.55 F. The studied terpenes and flavonoids compounds effectively thwart SdiA protein, therefore regulate inter- or intra cellular communication and associated virulence in Enterobacteriaceae, serving as prospective antivirulence drugs.
The involvement of Trypanosoma congolense sialidase alongside phospholipase A2 has been widely accepted as the major contributing factor to anemia during African animal trypanosomiasis. The enzymes aid the parasite in scavenging sialic acid and fatty acids necessary for survival in the infected host, but there are no specific drug candidates against the two enzymes. This study investigated the inhibitory effects of β-sitosterol on the partially purified T. congolense sialidase and phospholipase A2. Purification of the enzymes using DEAE cellulose column led to fractions with highest specific activities of 8016.41 and 39.26 µmol/min/mg for sialidase and phospholipase A2, respectively. Inhibition kinetics studies showed that β-sitosterol is non-competitive and an uncompetitive inhibitor of sialidase and phospholipase A2 with inhibition binding constants of 0.368 and 0.549 µM, respectively. Molecular docking of the compound revealed binding energies of − 8.0 and − 8.6 kcal/mol against the sialidase and phospholipase A2, respectively. Furthermore, 100 ns molecular dynamics simulation using GROMACS revealed stable interaction of β-sitosterol with both enzymes. Hydrogen bond interactions between the ligand and Glu284 and Leu102 residues of the sialidase and phospholipase A2, respectively, were found to be the major stabilizing forces. In conclusion, β-sitosterol could serve as a dual inhibitor of T. congolense sialidase and phospholipase A2; hence, the compound could be exploited further in the search for newer trypanocides. Graphical abstract
African animal trypanosomiasis (AAT) continues to wreak havoc on the livestock industry of the African continent causing a huge restriction on animal productivity. However, trypanocidal agents are faced with drawbacks necessitating the search for new drugs. Herein, we explore β-ionone as a potential candidate against AAT. Oral treatment with β-ionone (15 and 30 mg/kg Body Weight (BW) for 14 days significantly(P<0.05) reduced T. congolense proliferation, reverted anemia, and prevented the release of free serum sialic acid caused by the parasite while only 15 mg/kg BW β-ionone maintained 100% animals survival throughout the experimental period. Also, the increase in serum and tissues thiobarbituric acid reactive substances (TBARS) accompanied with decreased reduced glutathione (GSH) levels (except in the liver) as well as histopathological damages observed across tissues were significantly (P<0.05) ameliorated following treatment with both doses of β-ionone. Moreover, the compound also down-regulated the expression of T. congolense trans-sialidase gene variants (TconTS1, TconTS3, and TconTS4) with a positive correlation (P>0.05) between the serum-free sialic acid and the trans-sialidase variants. Using inhibition-kinetics, the compound interacted with T. congolense sialidase and phospholipase A2 via a mixed inhibition pattern with inhibition binding constants of 25.325 µM and 4.550 µM respectively while molecular docking predicted binding energies of -5.6 kcal/mol for both enzymes. From the present findings, it can be concluded that β-ionone possesses trypano-suppressive potentials and mitigates some of the trypanosome-induced pathologies, particularly anemia. Hence, the compound could serve as a structural scaffold for designing trypanocidal analogs with higher efficacy.
Vanillin (4-hydroxy-3-methoxybenzaldehyde) is a known natural aromatic flavoring agent and the major component of vanilla extracted from cured vanilla pods. Vanillin has several applications in foods, beverages, pharmaceuticals, perfumes and cosmetics. The Food and Drug Administration (FDA) and Flavor and Extract Manufacturers Association (FEMA) have recommended vanillin as safe and pose minimum detrimental consequences. Additionally, several studies have reported the pharmacological activities of vanillin including anticancer, antidiabetic, antioxidant, antisickling, antimicrobial, anti-inflammatory, aphrodisiac, cardio-protective, diuretic, amongst others. In spite of these interesting reports, the general perception of vanillin has been restricted to its role as a food additive. Therefore, we reviewed the pharmacological activities of vanillin to demonstrate its therapeutic potentials, especially as a component of functional foods. We further highlighted the biosynthesis, toxicity, bioavailability and other applications of the compound. Our review revealed that vanillin holds promising potentials in the prevention and cure of diverse human (metabolic and non-metabolic) diseases and is relatively bioavailable in the systemic circulation that could warrant a clinical trial.
Trypanosoma congolense is a pathogenic African animal trypanosome species causing devastating conditions leading to death of an infected host. The drawbacks of the existing trypanocidal drugs have led to the search for new drug candidates. In this study, β-ionone at 15 and 30 mg/kg Body Weight (BW) was orally administered to T. congolense infected rats for 14 days followed by an assessment of anaemia, organ damages and the expression of T. congolense trans-sialidase gene variants. A significant decrease in parasitemia (P<0.05) was observed in the animals treated with 15 mg/kg BW β-ionone besides increased animal survival rate. A trypanosome-induced decrease in Packed Cell Volume (PCV) and histopathological changes across tissues were significantly (P<0.05) ameliorated following treatment with both doses of β-ionone. This is in addition to reversing the parasite-induced upsurge in free serum sialic acid (FSA) and expression of T. congolense trans-sialidase gene variants (TconTS1, TconTS3 and TconTS4). Correlation analysis revealed a positive correlation (P>0.05) between FSA with the TconTS gene expressions. Additionally, the compound inhibited partially purified T. congolense sialidase and phospholipase A2 via mixed inhibition pattern with inhibition binding constants of 25.325 µM and 4.550 µM respectively, while molecular docking predicted binding energies of -5.6 kcal/mol for both enzymes. In conclusion, treatment with β-ionone suppressed T. congolense proliferation and protected the animals against some of the parasite-induced pathologies whilst the effect on anaemia development might be due to inhibition of sialidase and PLA2 activities as well as expression levels of TconTS3 and TconTS4.
Diterpenes are a diverse group of structurally complex natural products with a wide spectrum of biological activities, including antidiabetic potential. In the last 25 years, numerous diterpenes have been investigated for antidiabetic activity, with some of them reaching the stage of clinical trials. However, these studies have not been comprehensively reviewed in any previous publication. Herein, we critically discussed the literature on the potential of diterpenes as antidiabetic agents, published from 1995 to September, 2021. In the period under review, 427 diterpenes were reported to have varying degrees of antidiabetic activity. Steviol glycosides, stevioside (1) and rebaudioside A (2), were the most investigated diterpenes with promising antidiabetic property using in vitro and in vivo models, as well as human subjects. All the tested pimaranes consistently showed good activity in preclinical evaluations against diabetes. Inhibitions of α-glucosidase and protein tyrosine phosphatase 1B (PTP 1B) activities and peroxisome proliferator-activated receptors gamma (PPAR-γ) agonistic property, were the most frequently used assays for studying the antidiabetic activity of diterpenes. The molecular mechanisms of action of the diterpenes include increased GLUT4 translocation, and activation of phosphoinositide 3-kinase (PI3K) and AMP-activated protein kinase (AMPK)-dependent signaling pathways. Our data revealed that diterpenes hold promising antidiabetic potential. Stevioside (1) and rebaudioside A (2) are the only diterpenes that were advanced to the clinical trial stage of the drug discovery pipeline. Diterpenes belonging to the abietane, labdane, pimarane and kaurane class have shown promising activity in in vitro and in vivo models of diabetes and should be further investigated.
Glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC) of Trypanosoma brucei, the causative protozoan parasite of African trypanosomiasis, is a membrane-bound enzyme essential for antigenic variation, because it catalyses the release of the membrane-bound form of variable surface glycoproteins. Here, we performed a fragment-based drug discovery of TbGPI-PLC inhibitors using a combination of enzymatic inhibition assay and water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR experiment. The TbGPI-PLC was cloned and over-expressed using an Escherichia coli expression system followed by purification using three-phase partitioning and gel filtration. Subsequently, the inhibitory activity of 873 fragment compounds against the recombinant TbGPI-PLC led to the identification of 66 primary hits. These primary hits were subjected to the WaterLOGSY NMR experiment where 10 fragment hits were confirmed to directly bind to the TbGPI-PLC. These included benzothiazole, chlorobenzene, imidazole, indole, pyrazol and quinolinone derivatives. Molecular docking simulation indicated that six of them share a common binding site, which corresponds to the catalytic pocket. The present study identified chemically diverse fragment hits that could directly bind and inhibit the TbGPI-PLC activity which constructed a framework for fragment optimisation or linking towards the design of novel drugs for African trypanosomiasis.
Background and Introduction: COVID-19 has affected almost 180 million people around the world, causing the death of about 5 million persons, as of November 16, 2021. The disease presents with a plethora of pulmonary and extrapulmonary symptoms of varying severity. After an exhaustive review of the literature, we found no data on the mild and moderate COVID-19 disease phenotypes in Northern Nigeria. Our objective is to describe the clinical characteristics of non-severe COVID -19 disease phenotypes in Kano State. Methods: This is a retrospective cohort study at the COVID-19 Isolation Center of Muhammad Buhari Specialist Hospital Kano, Nigeria. We included all patients admitted from May 2020 to December 2020. Patients’ medical records were assessed and evaluated to describe the clinical characteristics at presentation. We explored time to discharge between patients aged ≤ 50 years old versus those >50. We applied the Kaplan-Meier product-limit estimator to generate cumulative probabilities of discharge over time and used the Log-rank test to determine differences between the two age groups. We applied Cox Proportional Hazards to identify predictors of time to discharge among the patients in the study. The study variables comprised of time of viral clearance and time to discharge as outcome variables, while main exposure variables included, age, sex, occupation, mode of exposure, presence of co-morbidity, and duration of hospitalization. Results: A total of 187 COVID-19 patients were reviewed. The commonest symptoms were fever, breathing difficulty, and dry cough. There was no recorded death. Contact with a confirmed COVID-19 positive person was the source of infection in 167(89.3%) of patients. We noted faster time to viral clearance in patients on lopinavir compared to those on chloroquine (Log-rank test p-value = 0.048). There were no significant differences in time to discharge between younger (< 50 years) versus older patients (≥ 50 years) [24 days vs. 26 days respectively; Log-rank test p-value = 0.082]. Age, sex, and source of infection did not appear to be predictors of infection phenotype. Conclusion and Implications for Translation: The findings of this study have a bearing on the surveillance and diagnosis of COVID-19 in Nigeria. While the plethora of clinical features may not be limited to infection with the SARS-CoV-2 virus, healthcare practitioners should consider these symptom clusters in addition to cognate contact and travel history when confronted with a suspected COVID-19 infection. Copyright © 2022 Maiyaki et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.
The search for a novel prophylactic agent against malaria is on the rise due to the negative socio-economic impact of the disease in tropical and subtropical regions of the world. Sequel to this, we evaluated the in vivo anti–Plasmodium berghei activity of a high-carbohydrate diet as well as the effects of the diet on parasite-associated anemia and organ damage. Mice were fed with either standard or a high-carbohydrate diet for 4 weeks and subsequently infected with chloroquine-sensitive strain of P. berghei. The levels of parasitemia, blood glucose, packed cell volume, and redox sensitive biomarkers of brain and liver tissues were measured. Data from this study showed that high-carbohydrate significantly (p < 0.05) aggravated the multiplication of P. berghei in the animals. Furthermore, our result demonstrated that blood glucose level in P. berghei–infected mice fed with a high-carbohydrate diet was insignificantly (p > 0.05) depleted. Additionally, our findings revealed that high-carbohydrate did not demonstrate a significant (p < 0.05) ameliorative potentials against P. berghei–induced anemia and oxidative stress in the brain and liver tissues. We concluded that high-carbohydrate diet was unable to suppress P. berghei upsurge and accordingly could not mitigate certain pathological alterations induced by P. berghei infection.
Purpose. Understanding some variations in specialized molecules during malaria could facilitate adequate monitoring of patients and reduce the fatalities caused by the disease. The present study reports changes in the levels of free serum sialic acid (FSSA) among Plasmodium-infected individuals in Zaria, Nigeria, in a cross-sectional study with 170 individuals. Methods. The FSSA and total sialic acid (TSA) in the blood were determined using the thiobarbituric acid method and the white blood cells (WBC) count, haemoglobin concentration and packed cell volumes were assessed using an automated haematological analyser. Results. The results showed that, in the patients aged > 5 years the level of TSA was significantly elevated (P < 0.05) compared to apparently healthy age-matched controls whereas TSA was slightly lower in patients aged < 5 years compared to controls. The ratio of FSSA to TSA was not different between patients aged > 5 years compared to their age-matched controls whereas FSSA/TSA was significantly elevated (P < 0.05) in patients aged < 5 years compared to their aged-matched controls. The level of FSSA/TSA in the patients aged < 5 years was not correlated with parasite density, white blood cell count, haemoglobin concentration or packed cell volume. Conclusion. We concluded that, metabolism and/or physiology of serum sialo-glycoconjugates is affected by malaria and FSSA is mainly elevated in children < 5 years of age but not among older patients suggesting the possible usefulness of FSSA in the analysis of uncomplicated malaria in under five children.
Background Recent COVID-19 outbreak has prompted the search of novel therapeutic agents to treat the disease. The initial step of the infection involves the binding of the virus through the viral spike protein with the host angiotensin converting enzyme 2 (ACE2). In this study, the interaction of some ACE or ACE2 inhibitors and their analogues as well as selected compounds with the viral spike protein as a strategy to hinder viral-ACE2 interaction were investigated. SARS-CoV-2 spike protein as well as the ligands were retrieved from protein databank and ChEBI database respectively. The molecules were prepared before initiating the virtual screening using PyRx software. Discovery studio was used to further visualize the binding interactions between the compounds and the protein. Results The ACE inhibitors and their analogues fosinopril (1-), fosinopril and moexipril have the best binding affinity to the protein with binding energies < − 7.0 kcal/mol while non-flavonoid stilben-4-ol binds with free binding energy of − 7.1 kcal/mol. Others compounds which belong to either the flavonoids, terpenes and alkaloid classes also have binding energies < − 7.0 kcal/mol. Such high binding energies were enhanced via hydrogen bond (h-bond) interactions in addition to other interactions observed between the compounds and the amino acid residues of the protein. Conclusions The ACE inhibitors and their analogues as well as the selected compounds could serve as inhibitors of the spike protein as well as lead in drug discovery processes to target the SARS-CoV-2 virus.
African trypanosomiasis is caused by Trypanosoma brucei subspecies and available drugs against it, are unsatisfactory due to poor pharmacokinetic properties. Trypanosomal Alternative Oxidase (TAO) is an attractive target for anti-trypanosome rational drug discovery because it is essential for parasite-specific ATP generation and absent in the mammalian host. In this study, 360 filtered ligands from the Universal Natural Product Database were virtually screened and docked on T. brucei brucei TAO (PDB-ID 3VVA). From the virtual screening, 10 ligands with binding energy from −10.6 to −9.0 kcal/mol were selected as hits and further subjected pharmacokinetic and toxicity analyses where all of them passed Lipinski’s rule of five. Also, the compounds were non-mutagenic, non-tumorigenic and could cross the blood brain barrier. The two topmost hits (UNPD29179; megacerotonic acid and UNPD41551; a quinazoline derivative) interacted with `four glutamates (Glu123, Glu162, Glu213 and Glu266) close to di-iron (2 iron elements) at the catalytic site of the enzyme. Subsequently, 100 ns MD simulations of the two topmost hits were performed using GROMACS where high RMSD values of 0.75 nm (TAO-UNPD29179) and 0.52 nm (TAO- UNPD41551), low residues fluctuations and consistent values of radius of gyration were observed. Moreover, Solvent Accessible Surface Area showed a consistent value of 160 nm² for both complexes while TAO-UNPD29179 had higher number of hydrogen bonds than the TAO-UNPD41551. Similarly, MM/PBSA calculations indicated that UNPD29179 had higher free binding energy with TAO than UNPD41551. The data suggest that megacerotonic acid and a quinazoline derivative could be potential inhibitors of TAO with improved pharmacokinetic properties. Communicated by Ramaswamy H. Sarma
Mageu is a fermented, non-alcoholic maize-derived product unique to southern Africa. The aim of this study was to identify the health benefits of a polyphenolic extract of commercially produced mageu related to the antioxidant properties and effects on lipid accumulation in differentiated 3T3-L1 adipocytes. A pooled sample of mageu Number 1 brand (original non-flavored) was subjected to in vitro gastroduodenal digestion (GDD). Reverse phase high-performance liquid chromatography of unfractionated undigested (UD) and GDD mageu revealed that with digestion there was an increased extraction of 1.2, 1.83, 1.45, 4.86, and 3.17-fold of caffeic acid, 3,4-dihydroxybenzoic acid, p-coumaric acid, 4 hydroxybenzoic acid and ferulic acid, respectively. An associated increase in the total phenolic acid content and antioxidant activity in the <3 kDa fraction was obtained. In contrast with digestion, inhibition of advanced glycation end products formation and low-density lipoprotein oxidation was found in the <30 kDa fraction indicating the contribution of larger, possibly feruloylated polysaccharides, to activity. Cellular antioxidant activity in Caco-2 cells was >90% for all UD fractions, but with GDD was reduced. All fractions had low scavenging of nitric oxide in the lipopolysaccharide/murine cell model. Exposure of 3T3-L1 adipocytes to all the UD and GDD mageu fractions (at 1% and 10% concentrations) during differentiation resulted in at least a 35% reduction in lipid accumulation, which was not associated with a loss of cellular viability. In conclusion, mageu, UD, and subjected to GDD contains phenolic acids with beneficial bioactive properties that contribute to antioxidant activity and reduces lipid accumulation in adipocytes. Practical applications Mageu is a non-alcoholic fermented maize product which when digested has increased bioactivity. Its reported health benefits are due to its caloric content therefore the practical application of this research is to validate the scientific benefits of this food and encourage increased consumption of this functional food. This is especially important in the context of the South African population where this product is widely consumed as increasing obesity is associated with an increased risk of non-communicable disease. Furthermore, as a non-alcoholic drink, consumption can be promoted for all ages’ groups and religions, and a commercialized manufacture processes can be optimized to increase phenolic acid release.
Interleukin (IL)-33 is a cytokine implicated in several inflammatory and autoimmune diseases. Upon binding to its receptor ST2, IL-33 activates allergic inflammatory responses. To block this protein-protein interaction with a potential anti-allergic agent, we screened Universal Natural Product Database (UNPD) using a combined approach of molecular docking and dynamic simulations. Six hundred compounds with high gastrointestinal absorption properties from the UNPD were retrieved and subjected to molecular docking using Autodock Vina, out of which four hetero-cyclic compounds (UNPD36, UNPD2045, UNPD8905, UNPD122514) were found to have binding energy score of < −7.0 Kcal/mol. Further analysis from 100 ns MD simulation of the best hit (UNPD36) revealed that IL-33_UNPD36 complex reached average stability at RMSD of 2.7 Å, and residues involved in the interaction showed lower fluctuations compared to the residues at the β4–β5 and β11–β12 loop region. Further molecular docking using Autodock 4.2 was carried out to determine the binding orientation of UNPD36. Using GROMACS, additional 50 ns MD simulations and MM-PBSA calculation were performed on this complex. Finally, chemoinformatic studies revealed that the UNPD36 had drug-like and pharmacokinetic profiles as well as potentials for oral and topical applications, in addition to good safety profile. Thus, it was concluded that a hetero-cyclic compound with chromone moiety (UNPD36) had a good and stable binding mode to serve as potential inhibitor of IL-33 and/or may provide a scaffold for further optimization toward the design of more potent inhibitors for application in the treatment of respiratory allergies. Communicated by Ramaswamy H. Sarma
Background Kolaviron (KV) is a flavonoid rich portion obtained from Garcinia kola seeds with a number of reported pharmacological effects. However, its ameliorative effects on 7,12-Dimethylbenzanthracene (DMBA)-induced mammary damage has not been fully investigated, despite the reported use of the seeds in the treatment of inflammatory related disorders. Objective To evaluate the ameliorative effects of KV on DMBA-induced mammary damage in female Wistar rats. Methods Forty-nine (49) female Wistar rats were randomly assigned into seven groups of seven rats each. DMBA was administered orally to rats in five of the groups as a single dose of 80 mg/kg body wt while the remaining two groups received the vehicle. The rats were palpated weekly for 3 months to monitor tumor formation. After 3 months of DMBA administration, 1 ml of blood was collected to assay for estrogen receptor- α (ER-α) level. Thereafter, the vehicle (dimethyl sulfoxide) was daily administered to the negative control and positive control groups for the 14 days duration of the experiment while three groups were each given a daily oral dose of 50, 100 and 200 mg/kg body wt of KV for the duration of the experiment. The last DMBA-induced group received 10 mg/kg body wt of the standard drug tamoxifen twice in a week and the remaining DMBA-free group received 200 mg/kg body wt KV. Subsequently, the animals were humanly sacrificed and ER-α, sialic acids, sialidase, sialyltransferase levels were assay for in blood and mammary tissues followed by histopathological examinations. Results Significantly higher levels of estrogen receptor-α (ER-α), formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration and increased sialylation were detected in DMBA-induced rats. Treatment with KV at 50, 100 and 200 mg/kg body weight resulted in a significant (p<0.05) decrease in ER-α level, significantly (p<0.05) lower free serum sialic acid (21.1%), total sialic acid level of the mammary tissue (21.57%), sialyltransferase activity (30.83%) as well as mRNA level of the sialyltransferase gene (ST3Gal1) were observed after KV interventions. Conclusion The findings suggest that KV could be further explored in targeting DMBA-induced mammary damage implicated in mammary carcinogenesis.
The parasite Trypanosoma brucei is the main cause of the sleeping sickness threatening millions of populations in many African countries. The parasitic infection is currently managed by some synthetic medications, most of them suffer limited activity spectrum and/or serious adverse effects. Some studies have pointed out the promising therapeutic potential of the plant extracts rich in polyphenols to curb down parasitic infections caused by T. brucei and other trypanosomes. In this work, the main components dominating Eugenia uniflora and Syzygium samarangense plant extracts were virtually screened, through docking, as inhibitors of seven T. brucei enzymes validated as potential drug targets. The in vitro and in vivo anti-T. brucei activities of the extracts in two treatment doses were evaluated. Moreover, the extract effects on the packed cell volume level, liver, and kidney functions were assessed. Five compounds showed strong docking and minimal binding energy to five target enzymes simultaneously and three other compounds were able to bind strongly to at least four of the target enzymes. These compounds represent lead hits to develop novel trypanocidal agents of natural origin. Both extracts showed moderate in vitro anti-trypanosomal activity. Infected animal groups treated over 5 days with the studied extracts showed an appreciable in vivo anti-trypanosomal activity and ameliorated in a dose dependent manner the anaemia, liver, and kidney damages induced by the infection. In conclusion, Eugenia uniflora and Syzygium samarangense could serve as appealing sources to treat trypanosomes infections.
The quest for the development of a novel antimalarial drug informed the decision to subject phytol to in vivo trials following a demonstration of therapeutic potential against chloroquine sensitive strain of Plasmodium falciparum under in vitro condition. On this basis, the in vivo anti-Plasmodium berghei activity of phytol including the ameliorative effects of the compound on P. berghei-associated anaemia and organ damage was investigated. Mice were infected with chloroquine-sensitive strain of P. berghei and were treated with phytol at a dose of 10 and 20 mg/kg body weight (BW) for four days. The levels of parasitemia, packed cell volume and redox sensitive biomarkers of liver, brain and spleen tissues were determined. Our result revealed that phytol significantly (p < 0.05) suppressed the multiplication of P. berghei in a dose-dependent manner. Additionally, the phytol significantly (p < 0.05) ameliorated the P. berghei-induced anaemia and brain damage. Data from the present study demonstrated that phytol has suppressive effect on P. berghei and could ameliorate some P. berghei-induced pathological changes.
Sialic acid and its associated metabolic enzymes have emerged as important components of the pathophysiology of type 2 diabetes (T2D). There is an elevation in the serum concentration of sialic acid in humans and animals with T2D. The present study investigated the modulation of mRNA expression level of UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) and neuraminidase 1 (NEU1) genes in some organs of type 2 diabetic rats. T2D was induced using fructose-streptozotocin model and eight weeks after the induction of diabetes, sialic acid was assayed in the blood and organs (adipose tissue, brain, colon, kidney, liver, pancreas, skeletal muscle and spleen) followed by quantification of mRNA expression level of GNE and NEU1 genes by qPCR. The results showed a significant (P < 0.05) increase in sialic acid level in the serum and all the afore-mentioned organs investigated except in the adipose tissue and skeletal muscle of the diabetic rats compared the normal control. The expression GNE gene was only increased in the pancreas (1.8-fold) of the diabetic rats while there was a decrease in the expression of the gene in the colon. In contrast, the expression of NEU1 gene was increased in the spleen (3.5-fold), brain (2.2-fold), liver (1.9-fold), colon (1.5-fold) and kidney of the diabetic rats. It was concluded that the elevated level of sialic acid in the organs of diabetic rats, except the pancreas, might not be due to increased endogenous synthesis of sialic acid.
Type 2 diabetes mellitus (T2DM) is a multifactorial disease that requires multiple therapeutic strategies for its management. Bioactive peptides with multiple anti-diabetic targets are attractive therapeutic molecules. The present study was conducted to identify additional anti-diabetic targets of α-glucosidase inhibitory peptides, SVPA, SEPA, STYV, and STY. The α-glucosidase inhibitory activity of the peptides was in the order STYV > STY > SEPA > SVPA while molecular docking against human dipeptidyl peptidase IV (DPP-IV) showed that SVPA had the best binding affinity. In contrast, in vitro studies indicated that SEPA had a significantly higher (P < 0.05) DPP-IV inhibitory activity (IC50 = 5.78 ± 0.19 mM) than other peptides. SVPA and SEPA showed mixed inhibition pattern while STYV and STY were uncompetitive inhibitors of the enzyme. IPI (diprotin A), STYV and STY were not cytotoxic while SEPA displayed some cytotoxicity. In differentiated 3T3-L1 adipocytes, SVPA and STYV were found to induce a significant (P < 0.05) decrease in intracytoplasmic lipid accumulation when added during the differentiation process while STY, GSH and IPI caused significant reduction (P < 0.05) in the lipid accumulation when added after the differentiation. The SVPA, SEPA and STYV were better scavengers of methylglyoxal than STY but STYV had the best scavenging activities toward reactive oxygen species and nitric oxide. It was concluded that the four α-glucosidase inhibitory peptides including IPI have multiple targets against type T2DM but, overall, of the four peptides evaluated, STYV tends to have better potential for application as a multifunctional anti-diabetic peptide.
In order for Plasmodium falciparum to grow and survive in its host, membrane biogenesis, fueled by host cholesterol, is essential for these processes. Consistent with this essential role, more insights into the cholesterol pathway would enhance the current understanding of the pathophysiology of malaria infection. To explore its broader potential, we conducted a cross-sectional study and assayed for the serum levels of cholesterol, vitamin D, progesterone, testosterone, estradiol and bile acid in both P. falciparum-infected patients and apparently healthy sex-matched participants. Our results revealed that the levels of cholesterol, vitamin D, progesterone, testosterone and estradiol in P. falciparum-infected patients were significantly (p < 0.05) lower compared to those in control groups whereas the level of bile acid in P. falciparum-infected patients was significantly (p < 0.05) higher compared to that in control groups. Additionally, cholesterol and the metabolic products with the exception of bile acid had a significant (p < 0.05) association with the parasite density in P. falciparum-infected patients with moderate and high P. falciparum infections. Furthermore, all the metabolic products of cholesterol had an insignificant (p > 0.05) association with the cholesterol in P. falciparum-infected patients with the exception of progesterone which showed a significant (p < 0.05) association with cholesterol in the malaria-infected female patients. Data from the present study demonstrated that progesterone depletion in P. falciparum-infected female patients could be a consequence of P. falciparum-induced decrease in cholesterol.
Background The analysis of single nucleotide polymorphism (SNPs) in drug-resistance associated genes is a commonly used strategy for the surveillance of anti-malarial drug resistance in populations of parasites. The present study was designed and performed to provide genetic epidemiological data of the prevalence of N86Y-Y184F-D1246Y SNPs in Plasmodium falciparum multidrug resistance 1 (pfmdr1) in the malaria hotspot of Northern Nigeria. Methods Plasmodium falciparum-positive blood samples on Whatman-3MM filter papers were collected from 750 symptomatic patients from four states (Kano, Kaduna, Yobe and Adamawa) in Northern Nigeria, and genotyped via BigDye (v3.1) terminator cycle sequencing for the presence of three SNPs in pfmdr1. SNPs in pfmdr1 were used to construct NYD, NYY, NFY, NFD, YYY, YYD, YFD and YFY haplotypes, and all data were analysed using Pearson Chi square and Fisher’s exact (FE) tests. Results The prevalence of the pfmdr1 86Y allele was highest in Kaduna (12.50%, ² = 10.50, P = 0.02), whilst the 184F allele was highest in Kano (73.10%, ² = 13.20, P = 0.00), and the pfmdr1 1246Y allele was highest in Yobe (5.26%, ² = 9.20, P = 0.03). The NFD haplotype had the highest prevalence of 69.81% in Kano (² = 36.10, P = 0.00), followed by NYD with a prevalence of 49.00% in Adamawa, then YFD with prevalence of 11.46% in Kaduna. The YYY haplotype was not observed in any of the studied states. Conclusion The present study suggests that strains of P. falciparum with reduced sensitivity to the lumefantrine component of AL exist in Northern Nigeria and predominate in the North-West region.
The present study was designed to investigate the role of methoxylation on the anti-diabetic potential of ρ-hydroxybenzaldehyde (ρ-BN) and its derivatives vanillin (VN) and syringaldehyde (SN) in type 2 diabetes (T2D). Fructose-fed streptozotocin-induced T2D rat model was used and orally treated with 50 and 100 mg/kg body weight of ρ-BN, VN and SN for 28 days. From the results, the diabetic control (DBC) group showed significant (p < 0.05) elevation in insulin resistance, blood glucose, fructosamine, glycogen phosphorylase (GP) activity, lipid profiles, and significant (p < 0.05) decrease in β-cell functions, insulin, liver glycogen contents, and glycogen synthase (GS) activity. The insulin receptor substrate-1 (IRS-1) and glucose transporter-4 (GLUT-4) mRNA expression in the hepatocyte and skeletal muscle were decreased in DBC compared to the normal control (NC) group. Oral treatment of the compounds improved the above diabetes-induced alterations to near normal and were comparable to the metformin treated group. Variation in methoxylation of ρ-BN, VN, and SN displayed an inconsistent pattern on the measured indices of diabetes (insulin resistance, β-cell functions, blood glucose, insulin, fructosamine, GS, GP, lipid profiles, IRS-1 and GLUT-4). However, in the case of oral glucose tolerance ability, serum insulin and fructosamine levels, liver glycogen contents and cardiovascular risk indices, the methoxylation mediated positive effects. The phenolic aldehydes (ρ-BN, VN, and SN) possessed anti-T2D activity while methoxylation partly influenced the anti-diabetic effects of the phenolic aldehyde skeleton.
Malaria and toxoplasmosis are two important parasitic diseases with significant public health concerns in the Sub‐Saharan African countries. Some aspects of pathogenesis of the two parasitic diseases involve the central nervous system manifesting neuropsychiatric disorders. Studies have implicated the single infection by Plasmodium spp. and Toxoplasma gondii in development of psychosis. Although concomitant infection of the two parasites suggests an aggravated psychotic condition, there is currently no reported study. This article reviewed some studies which implicated malaria and toxoplasmosis in psychosis. It further explored the likely role of concurrent infection by the parasites on psychosis, the dynamics of their pathology and possible effects of certain psychosis‐associated cytokines and other biomolecules on the central nervous system. We recommend evidence‐based research efforts in this field for the effective management of these two parasitic diseases to abate the public health burden of psychosis.
The quorum sensing (QS) mechanism has become a viable research strategy for the discovery of plant-derived anti-virulent agents to control drug-resistant bacteria. The increasing incidences of drug-resistant bacteria and the effort to curb it necessitate this study. We investigated the QS inhibitory potential of Centaurea praecox extracts on Chromobacterium violaceum (CV), antibacterial activity, and determination of chemical composition using GC-MS. C. praecox was subjected to sequential extraction using hexane (HEX), dichloromethane (DCM), ethyl acetate (EA), ethanol (ET), and aqueous (AQ) solvents. The extracts were subsequently evaluated for antibacterial activity using disc diffusion and QS violacein inhibition using spectrophotometry. The antibacterial effects of the extracts were moderate on gram-positive bacteria at 4 mg/mL in the order: HEX >EA >DCM >ET =AQ. However, the DCM extract demonstrated the most effective violacein inhibition of ≥80% at 0.3 mg/mL. QS violacein inhibitions were generally found to be concentration-dependent in the order: DCM >EA >HEX >ET =AQ with efficacies of ≥ 90% inhibition at ≥ 0.6 mg/mL. GC-MS analysis on the most potent DCM extract revealed N-vinylmethanimine, N-ethyl formamide, and propanamide among components identified. We concluded that C. praecox DCM extract contains bioactive chemicals as QS inhibitors and potential anti-virulent agents capable of combating the pathogenicity of drug-resistant bacteria in vivo.
Background The analysis of single nucleotide polymorphism (SNPs) in drug-resistance associated genes is a commonly used strategy for the surveillance of antimalarial drug resistance in populations of parasites. The present study was designed and performed to provide genetic epidemiological data of the prevalence of N86Y-Y184F-D1246Y SNPs in Plasmodium falciparum multidrug resistance 1 (pfmdr1) in the malaria hotspot of Northern Nigeria. Methods Plasmodium falciparum-positive blood samples on Whatman-3MM filter papers were collected from 750 symptomatic patients from four states (Kano, Kaduna, Yobe and Adamawa) in Northern Nigeria, and genotyped via BigDye (v3.1) terminator cycle sequencing for the presence of three SNPs in pfmdr1. SNPs in pfmdr1 were used to construct NYD, NYY, NFY, NFD, YYY, YYD, YFD and YFY haplotypes, and all data were analyzed using Pearson Chi-square and Fisher's exact (FE) tests. Results The prevalence of the pfmdr1 86Y allele was highest in Kaduna (12.5%, 𝜒² = 10.47, P < 0.05), whilst the 184F allele was highest in Kano (73.1%, 𝜒² = 13.20, P < 0.05), and the pfmdr1 1246Y allele was highest in Yobe (5.26%, 𝜒² = 9.18, P < 0.05). The NFD haplotype had the highest prevalence of 69.81% in Kano (𝜒² = 36.05, P < 0.05), followed by NYD with a prevalence of 49% in Adamawa, then YFD with prevalence of 11.46% in Kaduna. The YYY haplotype was not observed in any of the studied states. Conclusion The present study shows that P. falciparum strains with reduced sensitivity to artemether-lumefantrine exist in Northern Nigeria and predominate in the North-West region.
Background: The analysis of single nucleotide polymorphism (SNPs) in drug-resistance associated genes is a commonly used strategy for the surveillance of antimalarial drug resistance in populations of parasites. The present study was designed and performed to provide genetic epidemiological data of the prevalence of N86Y-Y184F-D1246Y SNPs in Plasmodium falciparum multidrug resistance 1 (pfmdr1) in the malaria hotspot of Northern Nigeria. Methods: Plasmodium falciparum-positive blood samples on Whatman-3MM filter papers were collected from 750 symptomatic patients from four states (Kano, Kaduna, Yobe and Adamawa) in Northern Nigeria, and genotyped via BigDye (v3.1) terminator cycle sequencing for the presence of three SNPs in pfmdr1. SNPs in pfmdr1 were used to construct NYD, NYY, NFY, NFD, YYY, YYD, YFD and YFY haplotypes, and all data were analyzed using Pearson Chi-square and Fisher's exact (FE) tests. Results: The prevalence of the pfmdr1 86Y allele was highest in Kaduna (12.50%, 𝜒² = 10.50, P = 0.02), whilst the 184F allele was highest in Kano (73.10%, 𝜒² = 13.20, P = 0.00), and the pfmdr1 1246Y allele was highest in Yobe (5.26%, 𝜒² = 9.20, P = 0.03). The NFD haplotype had the highest prevalence of 69.81% in Kano (𝜒² = 36.10, P = 0.00), followed by NYD with a prevalence of 49.00% in Adamawa, then YFD with prevalence of 11.46% in Kaduna. The YYY haplotype was not observed in any of the studied states. Conclusion: The present study shows that P. falciparum strains with potential reduced susceptibility to the lumefantrine component of AL exist in Northern Nigeria and predominate in the North-West region.
Background The analysis of single nucleotide polymorphism (SNPs) in drug-resistance associated genes is a commonly used strategy for the surveillance of anti-malarial drug resistance in populations of parasites. The present study was designed and performed to provide genetic epidemiological data of the prevalence of N86Y-Y184F-D1246Y SNPs in Plasmodium falciparum multidrug resistance 1 (pfmdr1) in the malaria hotspot of Northern Nigeria. Methods Plasmodium falciparum-positive blood samples on Whatman-3MM filter papers were collected from 750 symptomatic patients from four states (Kano, Kaduna, Yobe and Adamawa) in Northern Nigeria, and genotyped via BigDye (v3.1) terminator cycle sequencing for the presence of three SNPs in pfmdr1. SNPs in pfmdr1 were used to construct NYD, NYY, NFY, NFD, YYY, YYD, YFD and YFY haplotypes, and all data were analysed using Pearson Chi-square and Fisher's exact (FE) tests. Results The prevalence of the pfmdr1 86Y allele was highest in Kaduna (12.50%, 𝜒² = 10.50, P = 0.02), whilst the 184F allele was highest in Kano (73.10%, 𝜒² = 13.20, P = 0.00), and the pfmdr1 1246Y allele was highest in Yobe (5.26%, 𝜒² = 9.20, P = 0.03). The NFD haplotype had the highest prevalence of 69.81% in Kano (𝜒² = 36.10, P = 0.00), followed by NYD with a prevalence of 49.00% in Adamawa, then YFD with prevalence of 11.46% in Kaduna. The YYY haplotype was not observed in any of the studied states. Conclusion The present study suggests that strains of P. falciparum with reduced sensitivity to the lumefantrine component of AL exist in Northern Nigeria and predominate in the North-West region.
This 2-page POLICY BRIEF is the outcome of a rigorous review of literature and opinion-seeking exercise with students, lecturers and other relevant stakeholders across Nigerian Tertiary institutions on the ‘Sex for Grade’ menace. The policy brief is targeted at Policymakers and other stakeholders at the helm of affairs in Nigerian Tertiary institutions and Education ministries. The full paper is published and may be viewed at https://www.sciendo.com/article/10.2478/ast-2020-0008 OR https://www.researchgate.net/publication/342836087_A_Solution-Based_Position_Paper_of_the_Nigerian_Young_Academy_on_Sex-for-Grades_Menace_Across_Nigerian_Tertiary_Institutions
Objective The present study investigated the anti-Trypanosoma brucei brucei activity of methanolic extract of Senna occidentalis roots, leaves, stem bark, and seed in vitro and bioactive components of the most active plant part. Materials and methods Trypanosoma brucei brucei was identified by PCR, cultured in Dulbecco’s Modified Eagle Medium (DMEM) and incubated at 37 °C and 5% CO2. Subsequently, the cultured T. brucei brucei were incubated with 500 μg/ml concentration of different parts of S. occidentalis plant and the most potent fraction was identified and subjected to Gas Chromatography-Mass Spectrometry (GC-MS). Results Amplicons of the rRNA gene of T. brucei brucei detected had a size of 1200 bp. The anti-trypanosomal activities indicated that the root extract of the plant was the most active at 500 μg/ml with inhibitory activity of 88.89% and fractions (2 and 5) the most active with IC50 values of 1.49 and 1.16 μg/ml respectively. Conclusion Results from this study insinuates that phenolic and simple aliphatic compounds might play key role in the anti-trypanosomal activity of S. occidentalis roots.
The search for novel therapeutic candidates against animal trypanosomiasis is an ongoing scientific endevour because of the negative impacts of the disease to the African livestock industry. In this study, the in vivo therapeutic potentials of phytol toward Trypanosoma congolense infection and the inhibitory effects on trypanosomal sialidase were investigated. Rats were infected with T. congolense and administered daily oral treatment of 50 and 100 mg/kg BW of phytol. Within the first 10 days of the treatment, no antitrypanosomal activity was recorded but a moderate trypanostatic activity was observed from day 17-day 21 pi. However, at 100 mg/kg BW, phytol demonstrated a significant (p < 0.05) ameliorative potentials toward T. congolense-induced host-associated pathological damages such as anaemia, hepatic and renal damages; and the data was comparable to diminazine aceturate. Moreover, the T. congolense caused a significant (p < 0.05) increase in free serum sialic acid level which was significantly (p < 0.05) prevented in the presence of phytol (100 mg/kg BW). In an in vitro analysis, phytol inhibited partially purified T. congolense sialidase using an uncompetitive inhibition pattern with inhibition binding constant of 261.24 μmol/mL. Subsequently, molecular docking revealed that the compound binds to homology modelled trypanosomal sialidase with a binding free energy of −6.7 kcal/mol which was mediated via a single hydrogen bond while Trp324 and Pro274 were the critical binding residues. We concluded that phytol has moderate trypanostatic activity but with a great potential in mitigating the host-associated cellular damages while the anaemia amelioration was mediated, in part, through the inhibition of sialidase.
Type 2 diabetes is a multifactorial disease and drugs with multifunctional properties are required. The peptide, SQSPA, was reported to be a potent and gastrointestinally stable α-glucosidase inhibitory peptide. In this study, the structure-activity relationship of this peptide was studied using alanine scanning. Four analogs; AQSPA, SASPA, SQAPA and SQSAA were designed and investigated for multifunctional antidiabetic effects. Molecular docking studies on human dipeptidyl peptidase-IV (DPP-IV) suggested that the binding affinities were in the order; AQSPA>SASPA>SQSPA>SQSAA>SQAPA while for in vitro DPP-IV inhibitory activity, it was SQSPA>SQSAA>AQSPA>SASPA>SQAPA. Enzyme kinetic studies revealed that the peptides are uncompetitive inhibitors with the exception of SQSAA and SQSPA. In 3T3-L1 differentiated adipocytes, SASPA was the only analog that significantly (p < 0.05) reduced and prevented lipid accumulation and did not induce cytotoxicity to differentiated 3T3-L1 cells. All peptides, especially SASPA scavenged methylglyoxal and peroxyl radicals thereby preventing advanced glycosylated end products formation and oxidative stress. The nitric oxide scavenging activity of all peptides was comparable to IPI and glutathione. Findings indicate that the amide side chain of Q2 is probably the most critical functional group for modulating the multifunctional antidiabetic effects of SQSPA while SASPA has been identified, as a novel peptide with enhanced multifunctional antidiabetic activity.
Background Lemongrass (Cymbopogon citratus Stapf) tea is a widely consumed beverage for nourishment and the remedy of diabetes mellitus (DM) in Africa locally. The aim of the present study was to investigate the antidiabetic action of lemongrass tea (LGT) in a type 2 diabetes (T2D) model of rats. Methods The fructose-streptozotocin (STZ) animal model for T2D was used and the LGT was prepared by boiling for 10 min in water, allowed to cool and administered at 0.25 or 0.5% (ad libitum), for 4 weeks to the T2D rats. Results The LGT showed higher phytochemical contents compared to the cold-water extract. The diabetic untreated animals exhibited significantly (p < 0.05) higher serum glucose and lipids, insulin resistance (HOMA-IR) index with a significantly lower (p < 0.05) levels of serum insulin, β-cell function (HOMA-β) and liver glycogen compared to the normal animals. Oral supplemented of LGT for 4 weeks improved these changes comparable to the metformin treated group. Conclusion The data suggests that LGT intake had excellent antidiabetic effect in a T2D model of rats attributed to the higher content of the ingredients.
The present study was designed to review the antidiabetic potential of anthraquinones (AQs) with emphasis on the extent of blood glucose reduction, the half maximal inhibitory concentration values (in vitro studies), the proposed mechanisms of action, and the structure activity relationship studies. We sourced relevant data from the major scientific databases (Pubmed, Science Direct, Medline, and Google Scholar). According to our search, 25 AQs have shown variable antidiabetic potential, whereas one AQ (morindone‐6‐O‐β‐D‐primeveroside) showed no blood glucose‐lowering ability. Emodin and rhein showed the most promising antidiabetic potential in various models. The proposed mechanisms of antidiabetic action include upregulation of insulin receptor substrates‐1, phosphoinositide‐3‐kinase, and Akt‐ser473 expression and elevation of glucagon‐like peptide‐1 level in diabetic animal models linked to the potent protein tyrosine phosphatase 1B and dipeptidyl peptidase‐4 inhibitions. In addition, activation of peroxisome proliferator‐activated receptors gamma and inhibition of α‐glucosidase activity are other possible targets proposed as the mechanism of AQs antidiabetic action. The position and the number of hydroxyl group showed great influence on the overall antidiabetic potential of AQs. AQs hold promising antidiabetic activity despite scanty information. We hope that the present study will serve as a template to further explore the antidiabetic potential of AQs and subsequent antidiabetic drug development.
Aims: Chronic inflammation is associated with the production of high levels of proinflammatory cytokines via the JAK-STAT and NF-κB signalling pathways which are known to be inhibited by tofacitinib and aspirin respectively. High levels of these cytokines increase the synthesis of suppressors of cytokines (SOCS), which at high levels inhibit insulin signalling leading to insulin resistance. The effects of tofacitinib and aspirin on the degree of insulin resistance in type 2 diabetic rats were determined. Materials and methods: Rats were induced with type 2 diabetes (T2D) by administration of 10% fructose solution (ad libitum) followed by streptozotocin injection (40 mg/kg BW) and treated with different doses of tofacitinib (10 and 20 mg/kg BW), aspirin (100 and 200 mg/kg BW) and combination of the two drugs at both doses for 9 weeks. Key findings: Results showed that separate treatment with 10 mg/kg BW tofacitinib and 100 mg/kg BW aspirin significantly (P < 0.05) decreased tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6) and serum amyloid A when compared to diabetic untreated rats. However, the combined therapy (10 mg/kg BW tofacitinib and 100 mg/kg BW aspirin) significantly decreased the levels of TNF-α, IL-6, serum amyloid A, HOMA-IR, blood glucose level and SOC-3 gene expression but significantly (P < 0.05) improved glucose homoestasis, insulin secretion, HOMA-β and GLUT-4 gene expression when compared to diabetic untreated rat. Conclusion: It was concluded that simultaneous inhibition of the JAK-STAT and NF-κB signalling pathways with tofacitinib and aspirin respectively, could mitigate insulin resistance and hyperglycemia in T2D.
Ellagic acid has been previously found to possess trypanostatic effects and to alleviate some of organs' pathological complications, but it was not known whether these effects were mediated through an antioxidant-related mechanism or not. This work, therefore, investigates the effects of ellagic acid on lipid peroxidation and the antioxidants profile of Trypanosoma congolense-infected rats. The rats were infected with T. congolense and treated with ellagic acid (100 and 200 mg/kg body weight (BW)) and diminazine aceturate (3.5 mg/kg BW) for fourteen days; the remaining infected group was left untreated, while some animals were uninfected and untreated. The organs (liver, kidney, spleen, and heart) were harvested and homogenized, and malonyldialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase levels were measured. The MDA levels were significantly decreased (P ˂ 0.05) across all organs in the ellagic acid-treated groups compared to the infected untreated group. There was a significant increase (P ˂ 0.05) in the GSH levels in the group treated with 200 mg/kg BW of ellagic acid across all organs. However, treatment with ellagic acid did not significantly (P ˃ 0.05) change the SOD level compared to the infected untreated group in the liver of rats, but an increase was observed in the kidney, spleen, and heart of the treated groups. The 100 mg/kg BW of ellagic acid increased the catalase levels (P ˂ 0.05) in all organs except the kidney. This study concluded that ellagic acid boosted the endogenous antioxidant reserves and reduced lipid peroxidation.
The search for novel alpha-glucosidase inhibitory agents is currently an important scientific endeavour to the biopharmaceutical companies due to their potentials to reduce postprandial hyperglycaemia in type 2 diabetic patients. The present research attempted to investigate the alpha-glucosidase inhibitory effects of the leaf extract of Carica papaya. Aqueous, methanol, ethyl acetate and n-hexane extracts of C. papaya leaf were subjected to in vitro alpha-glucosidase inhibitory studies, and methanol extract was the most potent (IC50 = 171.83 ± 26.89 μg/mL). Consequently, the methanol extract was further fractionated by column chromatography which yielded six pooled fractions (A–F) and fraction A (FA) showed the lowest IC50 (78.62 ± 25.23 μg/mL). Subsequently, the FA was subjected to in vivo oral maltose and sucrose tolerance tests which revealed that FA had potent inhibitory effects on maltose and sucrose tolerance in rats. The computed area under the curves (AUC(0–120)) further indicates that FA (200 mg/kg bw) have better inhibitory activity on maltase than sucrase. The GC-MS analysis of FA indicates the presence of phenolics, various fatty acids and their derivatives. This research suggests that the leaf extract of C. papaya possesses alpha-glucosidase inhibitory effects and might be exploited in retarding postprandial hyperglycaemia.
Background Peptide-based therapeutics offer a unique avenue for the development of novel agents for the treatment of diabetes mellitus including α-glucosidase inhibitors. The peptide, SQSPA, was reported to possess to α -glucosidase inhibitory activity in addition to resistance to Gastrointestinal Tract (GIT) digestion. Methods In this study, the in silico and in vitro structure-activity analyses of the peptide was conducted using alanine scanning to identify key amino acid residues. Results The alanine scanning led to four analogs viz; AQSPA, SASPA, SQAPA and SQSAA which were GIT stable. Initially, the peptides were subjected to molecular docking on human α- glucosidase and α -amylase where the binding affinities to the enzymes were in the order; AQSPA>SASPA>SQSPA>SQAPA> SQSAA and AQSPA>SQSAA>SASPA>SQSPA> SQAPA, respectively. Hydrogen bond were important for the binding of all peptides but SASPA and AQSPA had the highest hydrogen bonds interactions with the α-glucosidase and α-amylase, respectively. In vitro analysis revealed that the α -glucosidase and α-amylase inhibitory activities of the peptides were in the order AQSPA>SQSPA>SQAPA>SASPA>SQSAA and AQSPA>SASPA> SQAPA>SQSPA>SQSAA, respectively. Using inhibition kinetics, SQSPA was a mixed inhibitor of α-glucosidase while AQSPA, SQAPA and SQSAA showed non-competitive inhibition. For α- amylase inhibition, SQSPA was a non-competitive inhibitor while AQSPA and SQSAA were mixed inhibitors; SASPA and SQAPA showed uncompetitive inhibition. Conclusion The results indicated that P4 and Q2 are important requirements for the α-glucosidase and α-amylase inhibitory activities of the parent peptide, SQSPA. Furthermore, alanine scanning has led to the design of a novel α-glucosidase inhibitory peptide, AQSPA, with increased activities.
This study investigated the restorative effect of Leea macrophylla ethanol root extract (LMERE) in carbon tetrachloride (CCl4) induced hepatic injury. It also tried to unfold the underlying mechanism through ligand-receptor interactions. Prior to conduct the CCl4 induced animal model study, the in vitro antioxidative capacities of LMERE were investigated. Gas chromatography mass spectroscopy (GC–MS) was accomplished to identify the prevalent bioactive compounds. The molecular docking was performed using Schrödinger Suites 2017-1. Results showed the promising antioxidative potentials of LMERE in in vitro models. Upon treatment of CCl4 intoxicated animals with LMERE, serum ALT and AST were found to be significantly (p < 0.05) reduced compared to the CCl4 control while LMERE50 was noted as the best dose in restoring the hepatic markers. Serum lipids and total protein were significantly restored compared to control. Remarkable changes of cell necrosis, apoptosis and sinusoidal dilution were noticed in histopathological assay of liver tissue. mRNA expression for superoxide dismutase (SOD1) and catalase was multifold increased which are statistically significant compared to reference drug, silymarin. In docking study, octadecanoic acid showed the lowest binding energy and highest binding affinity with the protein (ID: 1VKX) which is a crystallized structure of NF-κB p50/p65 heterodimer involved in cytokine production. The findings demonstrate that LMERE restores the hepatic damage by the mRNA expression of antioxidative enzymes while LMERE50, at a glance, seems the most suitable dose. Graphic abstract Open image in new window
In silico analysis was used to evaluate storage proteins from plant tubers as potential precursors of bioactive peptides after simulated gastrointestinal digestion. Proteins derived from potato (patatins), sweet potato (sporamins), yam (dioscorins) and taro (tarin) were subjected to in silico gastrointestinal digestion with a combination of pepsin, chymotrypsin and trypsin in the BIOPEP database which led to the release of 387 peptide fragments which were predicted to have bioactivities such as dipeptidyl peptidase IV (DPP-IV), angiotensin converting enzyme (ACE), antioxidative and antithrombotic activities. Prediction of antimicrobial activity of the released peptides using the collection of antimicrobial peptides (CAMP) database indicated 28 peptides as potential antimicrobial peptides (AMPs) with varied percentage similarity with known AMPs in antimicrobial peptide database (APD). Furthermore, 32 peptides with potential anticancer activity were predicted using the AntiCP database while nine peptides were predicted to be bioactive according to peptideRanker but the precise bioactivity was not identified. The potato-derived proteins seem to be the richest source of DPP-IV inhibitory and antimicrobial peptides while yam-derived proteins yielded the highest amount of antihypertensive and anticancer peptides. The data suggests that storage proteins from the selected plants could release an array of non-toxic and species-specific bioactive peptides with health promoting effects suggesting that these tubers might serve as functional foods.
Trypanosoma congolense is an important pathogen that wreaks havoc in the livestock industry of the African continent. This study evaluated the in vivo antitrypanosomal activity of geranylacetone and its ameliorative effect on the disease-induced anaemia and organ damages as well as its inhibitory effects against trypanosomal sialidase using in vitro and in silico techniques. Geranylacetone was used to treat T. congolense infected rats, at a dose of 50 and 100 mg/kg BW, for 14 days where it was found to reduce the parasite burden in the infected animals. Moreover, 100 mg/kg BW of geranylacetone significantly (p < 0.05) ameliorated the anaemia, hepatic and renal damages caused by the parasite. This is in addition to the alleviation of the parasite-induced hepatosplenomegaly and upsurge in free serum sialic acid levels in the infected animals which were associated with the observed anaemia amelioration by the compound. Consequently, bloodstream T. congolense sialidase was partially purified on DEAE cellulose column and inhibition kinetic studies revealed that the enzyme was inhibited by geranylacetone via an uncompetitive inhibition pattern. In silico analysis using molecular docking with Autodock Vina indicated that geranylacetone binds to trypanosomal sialidase with a minimum free binding energy of −5.8 kcal/mol which was mediated by 26 different kinds of non-covalent interactions excluding hydrogen bond whilst Asp163 and Phe421 had the highest number of the interactions. The data suggests that geranylacetone has trypanostatic activity and could protect animals against the T. congolense-induced anaemia through the inhibition of sialidase and/or the protection of the parasite-induced hepatosplenomegaly.
The present study was designed to conduct the bioassay-guided isolation of possible bioactive compound(s) responsible for the antidiabetic action of Xylopia aethiopica (Dunal) A. Rich. fruit. The isolation of compound was guided by α-glycosidase and α-amylase inhibitory activities. Molecular docking with Autodock Vina was used to decipher the mode of interaction and binding affinity of the possible compound(s) with the selected enzymes. A pentacyclic triterpene, oleanolic acid (OA) was isolated from fruit and exhibited significantly (P< 0.05) lower IC50 values (α-amylase: 89.02 ± 1.12 µM, α-glucosidase: 46.05 ± 0.25 µM) than other fractions and the acarbose. Interestingly, OA was found to bind to the α-amylase and α-glucosidase with minimum binding energy values of -0.9 and -1.2 kcal/mol respectively and none of the interactions involved hydrogen bond formation. It was concluded that OA is responsible for the antidiabetic action of X. aethiopica fruit through the inhibition of α-amylase and α-glucosidase activities.
The present study was designed to conduct the bioassay-guided isolation of possible bioactive compound(s) responsible for the antidiabetic action of Xylopia aethiopica (Dunal) A. Rich. fruit. The isolation of compound was guided by α-glycosidase and α-amylase inhibitory activities. Molecular docking with Autodock Vina was used to decipher the mode of interaction and binding affinity of the possible compound(s) with the selected enzymes. A pentacyclic triterpene, oleanolic acid (OA) was isolated from fruit and exhibited significantly (P< 0.05) lower IC50 values (α-amylase: 89.02 ± 1.12 µM, α-glucosidase: 46.05 ± 0.25 µM) than other fractions and the acarbose. Interestingly, OA was found to bind to the α-amylase and α-glucosidase with minimum binding energy values of -0.9 and -1.2 kcal/mol respectively and none of the interactions involved hydrogen bond formation. It was concluded that OA is responsible for the antidiabetic action of X. aethiopica fruit through the inhibition of α-amylase and α-glucosidase activities.
Non‐nutritive sweeteners (NNS) are increasingly being used by diabetics, but little is known about their effects on antioxidant status. We investigated the effects of ad libitum consumption of commercially available NNS (aspartame, saccharin, sucralose, and cyclamate‐based sweeteners) on antioxidative markers in a rat model of type 2 diabetes (T2D). NNS consumption reduced (p < 0.05) T2D‐induced lipid peroxidation and boosted serum, hepatic, renal, cardiac, and pancreatic glutathione (GSH) levels. Catalase, glutathione reductase, superoxide dismutase, and glutathione peroxidase activity was increased in the serum and most organs upon diabetes induction, perhaps due to adaptative antioxidant response to the diabetes‐induced lipid peroxidation. NNS showed varying effects on serum and tissue antioxidant enzymes of animals. An antioxidant capacity scores sheet of NNS, suggest that aspartame‐based NNS may not exert antioxidant effects in diabetics, while saccharin‐based NNS may be a potent antioxidative sweetener as seen in the animal model of T2D. Practical applications The use of NNS is becoming more popular, especially for diabetic individuals. While there are several commercial NNS available in the market, little is known about how they affect the antioxidant status of consumers. We therefore investigated how some commercially available NNS affect the antioxidant status of diabetic rats. Observed data revealed varying effects of NNS on serum and different organs, which suggest that some NNS may be better than others for diabetic oxidative stress and thus may be recommended for consumers. However, this finding is subject to additional corroborative clinical studies.
Ethnopharmacological relevance: Diabetes and hypertension are pathophysiologically related diseases that co-exist with a wider complex of metabolic diseases having similar set of risk factors. There are numerous ethnopharmacological evidences on the anti-diabetic and/or anti-hypertensive properties of medicinal plants from various parts of the world, which are used as therapies to concomitantly manage diabetes and hypertension. Aim of the review: This article reviewed findings on medicinal plants with both anti-diabetic and anti-hypertensive effects reported in same experimental study to facilitate the development of dual-acting therapies against diabetes and hypertension. Materials and methods: A literature search was carried out on different scientific search engines including, but not limited to “PubMed”, “Google Scholar”, “Scopus” and ScienceDirect to identify published data in which plants in same experimental studies were reported to possess both anti-hyperglycemic and anti-hypertensive effects. Subsequently, the anti-diabetic/anti-hypertensive potency ratio (ψ) of the medicinal plants was computed. Results: Sixty-four studies with 102 plant species matched the selection criteria. Members of the Fabaceae family were the most investigated plants, while the ψ greatly varied across the plants, with only 11 plants having a ψ ≃ 1. Withania somnifera Dunal was the only plant reported to show blood glucose-lowering and diuretic effects in humans, comparable to daonil. Caffeic acid, chlorogenic acid, caftaric acid, cichoric acid, verbascoside, leucosceptoside A, isoacteoside, fucoxanthin and nicotinamide were the reported dual acting anti-diabetic and anti-hypertensive compounds identified and/or isolated in the plants. Conclusions: This review suggests that medicinal plants possess varied therapeutic dynamics against hypertension and diabetes that could be exploited for the discovery of therapeutic preparation(s) or agent(s) for treating the two diseases.
Terpenoids are the largest and structurally most diverse group of secondary metabolites derived from natural sources. Empirical evidence from several bioassays points to the therapeutic potentials of terpenoids against protozoan parasitic diseases such as malaria, trypanosomiasis, and leishmaniasis. The versatility of the parent terpenoid backbones allows for structural diversity among the group, which in turn leads to multiple cellular targets and consequently varying mechanisms of antiparasitic action. Available data implicate disruption of parasite cell membrane architecture, interference with mitochondrial respiration, interaction with various crucial proteins of the parasites among other probable mechanisms. Identification of the specific cellular targets vis-á-vis the mechanisms of action of the different terpenoids will aid the design of novel and safer antiparasitic agent(s). This chapter therefore aims to discuss parasites-related cellular targets of terpenoids and their mode of antiparasitic activity. We hope that the chapter will be a valuable source of useful information in the exploration of the full potential of terpenoids as antiparasitic agents.
The paper is a presentation made at 34th NSBMB Conference, Minna 2015 on investigation of the effects of combined administration of red palm oil feed supplement and aqueous extract of roselle calyx (zobo) on hepatic and renal functions of T.b.brucei infected rats.
Antidiabetic agents with multiple targets have the greatest pharmaceutical potential. In this study, three α-glucosidase inhibitory peptides, PFP, YPL and YPG, were investigated for additional antidiabetic targets viz.; dipeptidyl peptidase-IV inhibition (DPP-IV), lipid accumulation and the differentiation of 3T3-L1 adipocytes, and scavenging of methylglyoxal (MGO), reactive oxygen species (ROS) and nitric oxide (NO). The peptides were subjected to molecular docking on human DPP-IV where the binding free energies were PFP < YPG < YPL < diprotin A while hydrogen bond interactions were critical in the binding of YPL and YPG. Moreover, YPG demonstrated significantly higher (p < 0.05) in vitro DPP-IV inhibition than PFP and YPL. Kinetic analysis revealed that all three peptides are uncompetitive inhibitors of DPP-IV while YPG had the lowest inhibition binding constant. PFP and YPG prevented lipid accumulation in 3T3-L1 differentiated adipocytes but may be due to cytotoxicity for PFP. The peptides scavenged MGO, ROS and NO but only the ROS and NO scavenging activities of YPG were comparable to glutathione. In conclusion, PFP, YPL and YPG exhibited DPP-IV inhibitory activity, reduced adipocyte differentiation and lipid accumulation as well as scavenged MGO, ROS and NO. However, YPG had the best potential as a possible multifunctional antidiabetic agent.
Bauhinia rufescens aerial parts have been successfully utilized in rural settings to overcome toxicity associated ailments in animals many decades ago. Recently, overdose of acetaminophen has been reported to cause severe hepatic and renal injuries in experimental animals and humans. This study evaluated the acute hepato-renal curative effects of methanol (MeOH) and ethylacetate (EtoAc) extracts of B. rufescens Lam leaf against acetaminophen-induced toxicity in rats following an experimental period of 10 days. Thirty six Wistar rats were randomly allocated into nine groups for the study. The acetaminophen toxic groups were orally administered with 2g/kg body weight acetaminophen for four days before the commencement of treatment on day 5 post-intoxication with either of 100 and 200mg/kg body weight of the two extracts. Hepato-renal toxicity was ascertained by evaluation of changes in serum alanine aminotransferase, aspartate aminotransferase, total protein, urea, creatinine, glucose, cholesterol, HDL-cholesterol and triglycerides. Acetaminophen-induced hepato-renal toxicity was biochemically manifested by significant increases (p<0.05) in the levels of the above biochemical indices with the exception of total protein which showed marked significant (p<0.05) decrease. Treatment by the two extracts significantly (p<0.05) restored the altered biochemical indices to near normal with MeOH extract being greater compared to the EtoAc extract. The results obtained suggested that B. rufescens leaf extract possess the ability to mitigate acute hepato-renal toxicity in acetaminophen intoxicated rats.
Treatment of type 2 diabetes is achieved through the inhibition of carbohydrate hydrolyzing enzymes such as α-glucosidase and α-amylase. The present study was conducted to identify novel α-glucosidase inhibitory peptides and to validate the α-glucosidase and α-amylase inhibitory activities of two promising candidates. A total of 4210 potential α-glucosidase inhibitory peptides with 3-5 amino acid residues were designed and individually subjected to in silico simulated gastrointestinal (GIT) digestion using the BIOPEP database. Subsequently, 844 GIT resistant peptides were then subjected to molecular docking using Autodock Vina to determine their binding free energy against human α-glucosidase (PDB ID: 3L4Y). Among all the peptides, SVPA and SEPA were found to have the lowest binding free energies of -8.7 and -8.6 kcal/mol, respectively. Docking of SVPA and SEPA on human α-amylase (PDB ID, 4GQR) identified that both peptides also bind to α-amylase with binding energies of -6.5 and -6.9 kcal/mol, respectively. Hydrogen bond interactions were critical for the binding of both peptides to the α-glucosidase and α-amylase. In vitro, SVPA and SEPA inhibited α-glucosidase and α-amylase activities with IC50 values several fold lower than acarbose except for SVPA that had a significantly higher (p < 0.05) IC50 value than acarbose against α-glucosidase. Lineweaver-Burk analyses revealed that SVPA was an uncompetitive inhibitor of the two enzymes, while SEPA inhibited α-glucosidase and α-amylase non-competitively and uncompetitively, respectively. This study has identified two novel and active α-glucosidase inhibitory peptides that could resist GIT digestion and therefore, have the potential to retard postprandial hyperglycemia in diabetic patients.
Background Trypanosomiasis is one of the neglected tropical diseases and continues to cause serious morbidity, mortality and economic loss. Current anti-trypanosomal drugs are antiquated and suffer from a number of serious setbacks, thereby necessitating the search for new drugs. Stigmasterol has previously demonstrated in vitro and in vivo anti-trypanosomal activity. Methods Herein, stigmasterol was docked into three validated anti-trypanosomal drug targets; uridylyl transferase, farnesyl diphosphate synthase and sterol 14α-demethylase, in order to elucidate the possible biochemical targets for the observed anti-trypanosomal activity. Results The binding free energy between stigmasterol and the enzymes was in the order; sterol 14α-demethylase (-8.9 kcal/mol) < uridylyl transferase (-7.9 kcal/mol) < farnesyl diphosphate synthase (-5.7 kcal/mol). At the lowest energy docked pose, stigmasterol interacts with the active site of the three trypanosomal enzymes via non-covalent interactions (apart from hydrogen bond) while highly hydrophobic stigmasterol carbon atoms (21 and 27) were crucial in the interaction with varying residues of the three anti-trypanosomal targets. Conclusion Therefore, results from this study might suggest that stigmasterol mediated the antitrypanosomal activity through interaction with the three anti-trypanosomal targets but with more preference towards sterol 14α-demethylase.
Context: Ziziphus mucronata Willd (Rhamnaceae) is currently used in Nigerian traditional treatment of diabetes mellitus. However, detailed information on the antidiabetic potential of the plant parts is presently unknown. Objectives: The present study investigated the antidiabetic effects of the butanol fraction of Z. mucronata root (ZMBF) in a type 2 diabetes (T2D) model of rats. Materials and methods: T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by an intraperitoneal injection of streptozotocin (40 mg/kg bw) and the animals were orally treated with ZMBF 150 or 300 mg/kg bw for five days a week for four weeks. Food and fluid intake, body weight changes and blood glucose levels were monitored during the experiment while other blood and organ specific diabetes-associated parameters were measured at the end of the experiment. Results: After four-week treatment, significantly (p < 0.05) lower blood glucose (19.24 vs 28.96 mmol/L), improved glucose tolerance ability (21.26 vs 28.56 mmol/L), higher serum insulin (131.37 vs 64.20 pmol/L) and liver glycogen (2.40 vs 1.54 mg/g tissue) were observed in the 300 mg/kg ZMBF ingested group compared with the diabetic control group. However, food and fluid intake, body weight gain, HOMA-β, HOMA-IR, serum fructosamine level, hepatic and renal function tests were not significantly (p > 0.05) affected by the treatment of ZMBF. Conclusion: Results of this study suggest that ZMBF treatment, at 300 mg/kg bw, possess antidiabetic activity, but could not ameliorate some diabetes-related parameters in type 2 diabetic rats.
The relationship between the degree of hyperglycaemia and glucose-6-phosphate dehydrogenase (G6PD) activity was investigated in patients with type 2 diabetes (T2D) attending Aminu Kano Teaching Hospital, Kano, Nigeria. The study subjects consisted of thirty patients with T2D between the ages of 30–50 years who were divided into low glycaemia group (LGDG; n = 14), with fasting blood glucose (FBG) level ≤ 7 mM and high glycaemia group (HGDG; n = 16)with FBG level > 7 mM. Ten apparently healthy age and sex-matched individuals served as the normal control group (NCG; n = 10). The FBG, G6PD activity and thiobarbituric acid reactive substances (TBARS) level were determined for all subjects. The HGDG had a significant (P < 0.05) 3-fold higher FBG level (12.78 ± 3.10 mM) compared to NCG (4.62 ± 0.55 mM) while the LGDG had an insignificant (P > 0.05) FBG level (6.10 ± 0.76 mM) compared to the NCG. Conversely, the HGDG had a significantly (P < 0.05) 2-fold lower plasma G6PD activity (24.85 ± 10.72 mU/gHb) compared with the NCG (55.21 ± 10.20 mU/gHb) with no significant difference in the plasma G6PD activity of the LGDG (55.25 ± 18.05 mU/gHb) compared to the NCG. Correlation analyses revealed a strong negative correlation (r = − 0.75) between FBG level and plasma G6PD activity in the HGDG only and not in the LGDG. The data suggests that reduced G6PD activity in the plasma of type 2 diabetic patients in Kano, Nigeria, is mainly associated with poor glycemic control.
Background: Cancer is a multifaceted metabolic disease that affects sizeable dwellers of rural and urban areas. Among the various types of cancer, mammary cancer is one of the most frequently diagnosed cancers in women. Its menace can be curbed with locally consumed spices due to their multiple bioactive phytochemicals. Aims: This review focuses on the breast cancer chemopreventive and therapeutic potentials of locally consumed spices. Methods/results: The most commonly consumed spices with breast cancer chemopreventive and chemotherapeutic phytochemical include pepper, onions, ginger, garlic, curry and thyme containing many biologically active metabolites ranging from vitamins, fatty acids esters, polyphenols/phenolics, sulfurcontaining compounds and anthraquinones with proven antioxidant, anti-inflammatory, immuno-modulatory, antitumor and anticancer properties against breast cancer/carcinogenesis. Therefore, extracts and active principles of these spices could be explored in breast cancer chemoprevention and possibly therapeutically which may provide an avenue for reducing the risk and prevalence of breast cancer.
Bioactive peptides are emerging as promising class of drugs that could serve as α-glucosidase inhibitors for the treatment of type 2 diabetes. This article identifies structural and physicochemical requirements for the design of therapeutically-relevant α-glucosidase inhibitory peptides. So far, a total of 43 fully sequenced α-glucosidase inhibitory peptides have been reported and 13 of them had IC50 values several folds lower than acarbose. Analysis of the peptides indicates that the most potent peptides are tri- to hexapeptides with amino acids containing a hydroxyl or basic side chain at the N-terminal. The presence of proline within the chain and alanine or methionine at the C-terminal appears to be relevant for high activity. Hydrophobicity and isoelectric points are less important variables for α-glucosidase inhibition while a net charge of 0 or +1 was predicted for the highly active peptides. In silico simulated gastrointestinal digestion revealed that the high and moderately active peptides, including the most potent peptide (STYV), were gastrointestinally unstable, except SQSPA. Molecular docking of SQSPA, STYV and STY (digestion fragment of STYV) with α-glucosidase suggested that their hydrogen bonding interactions and binding energies were comparable with acarbose. The identified criteria will facilitate the design of new peptide-derived α-glucosidase inhibitors. This article is protected by copyright. All rights reserved.
The quest to find new lead compounds with anti-diabetic effects via the inhibition of α-glucosidase and α-amylase had led us to conduct bioassay guided isolation of three African medicinal plants which resulted in the identification of bicyclo[2.2.0]hexane-2,3,5-triol (1), 3β-O-acetyl betulinic acid (2) and 2,7-dihydroxy-4H-1-benzopyran-4-one (3), as the bioactive compounds. The compounds demonstrated a significant (P < 0.05) inhibitory effect on α-glucosidase and α-amylase activities than acarbose. Steady state kinetic analysis revealed that compounds 1 and 2 inhibited both α-amylase and α-glucosidase in noncompetitive patterns whilst compound 3 was an uncompetitive inhibitor of α-glucosidase and a non-competitive inhibitor of á-amylase. In conclusion, the study has identified three new active α-glucosidase and α-amylase inhibitory compounds that could have the potential to retard postprandial hyperglycemia.
Leishmaniases are endemic diseases in tropical and sub-tropical regions of the world and considered to be among the six most important neglected tropical diseases by the World Health Organization (WHO). The current therapeutic arsenal against the disease suffers from series of chemotherapeutic setbacks. However, since the early 1990s, naturally occurring chalcones with promising antileishmanial effects have been reported and several other synthetic chalcones and chalcone-hybrid molecules were confirmed to possess potent activity against various Leishmania species. Herewith, a comprehensive review covering the antileishmanial activity of 34 naturally occuring chalcones, 224 synthetic/semisynthetic chalcones and 54 chalcone hybrid molecules, is presented. Several chalcones in the synthetic/semisynthetic category had IC50 values < 5µM with very good selectivity against parasites and the structure activity relationships as well as the proposed mechanism of action were discussed. We identified knowledge-gaps with the hope of providing future direction for the discovery of novel antileishmanial drugs from chalcones.
Background: The search for novel antitrypanosomal agents had previously led to the isolation of ellagic acid as a bioactive antitrypanosomal compound using in vitro studies. However, it is not known whether this compound will elicit antitrypanosomal activity in in vivo condition which is usually the next step in the drug discovery process. Purpose: Herein, we investigated the in vivo activity of ellagic acid against bloodstream form of Trypanosoma congolense and its ameliorative effects on trypanosome-induced anemia and organ damage as well as inhibitory effects on trypanosomal sialidase. Methods: Rats were infected with T. congolense and were treated with 100 and 200mg/kg body weight (BW) of ellagic acid for fourteen days. The levels of parasitemia, packed cell volume and biochemical parameters were measured. Subsequently, T. congolense sialidase was partially purified on DEAE cellulose column and the mode of inhibition of ellagic acid on the T. congolense sialidase determined. Molecular docking study was also conducted to determine the mode of interaction of the ellagic acid to the catalytic domain of T. rangeli sialidase. Results: At a dose of 100 and 200mg/kg (BW), ellagic acid demonstrated significant (P < 0.05) trypanosuppressive effect for most of the 24 days experimental period. Further, the ellagic acid significantly (P < 0.05) ameliorated the trypanosome-induced anemia, hepatic and renal damages as well as hepatomegaly, splenomegaly and renal hypertrophy. The trypanosome-associated free serum sialic acid upsurge alongside the accompanied membrane bound sialic acid reduction were also significantly (P < 0.05) prevented by the ellagic acid treatment. The T. congolense sialidase was purified to a fold of 6.6 with a yield of 83.8%. The enzyme had a KM and Vmax of 70.12mg/ml and 0.04µmol/min respectively, and was inhibited in a non-competitive pattern by ellagic acid with an inhibition binding constant of 1986.75μM. However, in molecular docking study, ellagic acid formed hydrogen bonding interaction with major residues R(39), R(318), and W(124) at the active site of T. rangeli sialidase with a predicted binding free energy of -25.584kcal/mol. Conclusion: We concluded that ellagic acid possesses trypanosuppressive effects and could ameliorate the trypanosome-induced pathological alterations.
The phenolics-rich fraction of Khaya senegalensis A. Juss (Meliaceae) stem bark extract (pfks) has been previously reported to possess potent antitrypanosomal activity at 300 mg/kg body weight (bw) but could not completely prevent disease-induced anemia and organ damage in addition to being slightly hepatotoxic at the same dose. Therefore, the effects of a combined administration of low dose pfks and vitamin C on the severity of Trypanosoma brucei brucei infection in rats were investigated. Daily oral administration of a combined treatment of pfks (100 mg/kg bw) and vitamin C (100 mg/kg bw) for seven days significantly (p < 0.05) reduced the number of T. brucei brucei in the bloodstream compared to infected untreated control with an ED50 of 51.15 mg/kg bw. Also, the trypanosome-induced pathological alterations such as anemia, hepatic and renal damages were significantly (p < 0.05) prevented by the same dosage of the combined treatment. Thus, the results obtained suggest that the combined treatment of a low dose of pfks and vitamin C is therapeutically potent as antitrypanosomal regimen and could effectively ameliorate the trypanosome-induced anemia and organ damage.
BACKGROUND: Breast cancer has been reported to be among the frequently diagnosed cancer in women worldwide despite advances in early detection and treatment. Several drugs are currently used for chemoprevention as a result of a number of drawbacks associated with breast cancer therapy. AIM: This review focuses on the metabolism and toxicological implications of these drugs against breast cancer/carcinogenesis. METHODOLOGY: Relevant articles on the commonly used anti-breast cancer drugs (raloxifene, tamoxifen, anastrozole, letrozole and exemestane) used in chemoprevention were searched using the major scientific databases including Scopus, Embase, PubMed/ Medline, Sciencedirect and Google Scholar. RESULTS: The mechanism of action of estrogen receptor modulators are basically mediated via binding to estrogen receptors leading agonistic and antagonistic effects, whereas that of aromatase inhibitors involved the suppression of estrogen concentration in plasma via inhibition or inactivation of aromatase. Both estrogen receptor and aromatase modulators are good candidates for breast cancer chemoprevention, with latter being the most appropriate. However, it has been observed that pharmacodynamics nature of these xenobiotics, often yields some undesirable outcomes after administration which may be linked to resistance and other biological side effects, following phase I/II reactions, bioactivation within and around breast tissue microenvironment vis-à-vis distant tissues. Various findings indicated the manifestation of genotoxicity, organ toxicity and oxidative/nitrosative stress at low, moderate and high doses, thereby complicating the already existing precarious condition. Moreover, interindividual variations were also observed amongst patients, suggesting a critical role of genetic polymorphism. Also, variable side effects including osteoporosis, musculoskeletal events, such as arthralgia and myalgia were found to be predominant. CONCLUSION: The aromatase inhibitors seem to be most appropriate when it comes to application by virtue of their metabolic functions and fates. The reason is that raloxifene and tamoxifen are not the ideal drugs to reduce the incidence of primary invasive breast cancer because their safety and efficacy don't reach the desired optimal agent level. However, adequate care should be taken while prescribing, as well as during and after treatment with constant close monitoring of patients for any possible biochemical and clinical manifestations vis-à-vis the issue of pharmacogenetics.
The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC50 = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU50 = 2.68 ± 0.75 %) or without (GU50 = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.
Vitex doniana is an important African medicinal plant traditionally used for the treatment of many diseases including type 2 diabetes (T2D). In this study, ethyl acetate, ethanol and aqueous extracts of the stem bark, root and leaf of V. doniana were analyzed for in vitro anti-oxidative activity and the results indicated that the ethanolic extract of the leaves had the best anti-oxidative activity. Subsequently, the ethanolic extract of the leaves was partitioned between hexane, dichloromethane, ethyl acetate and water. The aqueous fraction had a significantly (p < 0.05) higher phenolics content and also showed the best anti-oxidative activity within the fractions. Furthermore, the aqueous fraction demonstrated significantly (p < 0.05) more potent inhibitory activities against α-glucosidase and α-amylase than other fractions. Steady state kinetics analysis revealed that the aqueous fraction inhibited both α-glucosidase and α-amylase activities in a non-competitive manner with inhibition binding constant (Ki) values of 5.93 and 167.44 μg/mL, respectively. Analysis of the aqueous fraction by GC-MS showed the presence of resorcinol, 4-hydroxybenzoic acid, 3,4,5-trimethoxyphenol and 2,4′-dihydroxychalcone identified by their mass fragmentation patterns and comparison to standard spectra. The results obtained in this study showed that V. doniana leaves have a good in vitro anti-T2D potential possibly elicited through phenolics.
This study investigated the effects of maltitol on intestinal glucose absorption and muscle glucose uptake using ex vivo and in vivo experimental models. The ex vivo experiment was conducted in isolated jejunum and psoas muscle from normal rats. The in vivo study investigated the effects of a single bolus dose of maltitol on gastric emptying, intestinal glucose absorption and digesta transit in normal and type 2 diabetic rats. Maltitol inhibited glucose absorption in isolated rat jejunum and increased glucose uptake in isolated rat psoas muscle in the presence of insulin but not in the absence of insulin. In contrast, maltitol did not significantly (p > 0.05) alter small intestinal glucose absorption or blood glucose levels as well as gastric emptying and digesta transit in normal or type 2 diabetic rats. The results suggest that maltitol may not be a suitable dietary supplement for anti-diabetic food and food products to improve glycemic control.
Parasitic infections are among the leading global public health problems with very high economic and mortality burdens. Unfortunately, the available treatment drugs are beset with side effects and continuous parasite drug resistance is being reported. However, new findings reveal more promising compounds especially of plant origin. Among the promising leads are the pentacyclic triterpenes (PTs) made up of the oleanane, ursane, taraxastane, lupane and hopane types. This paper reviews the literature published from 1985 to date on the in vitro and in vivo anti-parasitic potency of this class of phytochemicals. Of the 191 natural and synthetic PT reported, 85 have shown high anti-parasitic activity against various species belonging to the genera of Plasmodium, Leishmania, Trypanosoma , as well as various genera of Nematoda. Moreover, structural modification especially at carbon 3 (C3) and C27 of the parent backbone of PT has led to improved anti-parasitic activity in some cases and loss of activity in others. The potential of this group of compounds as future alternatives in the treatment of parasitic diseases is discussed. It is hoped that the information presented herein will contribute to the full exploration of this promising group of compounds as possible drugs for parasitic diseases.
BACKGROUND: Inhibition of intestinal maltase and sucrase prevents postprandial blood glucose excursions which is beneficial in ameliorating diabetes-associated complications. OBJECTIVE: In this study, the inhibitory effects of fruit extracts of Parinari macrophylla, Detarium microcarpum, Ziziphus spina-christi, Z. mairei and Parkia biglobosa were investigated against intestinal maltase and sucrase. METHODS: Rats were given co-administration of the fruit extracts with maltose or sucrose and blood glucose levels were measured at 0, 30, 90 and 120 min. RESULTS: The glucose-time curves indicated that all the fruits had the most potent inhibitory effects on both maltase and sucrase within the first 30 min. The computed Area Under the Curves (AUC0-120) for all the fruits indicated more potent inhibitory effects against intestinal maltase than sucrase. The ED50 range for the fruits extract against maltase and sucrase were 647.15-1118.35 and 942.44-1851.94 mg/kg bw respectively. CONCLUSION: The data suggests that the fruits could prevent postprandial hyperglycemia via inhibition of intestinal maltase and sucrase.
Trypanosomiasis is a serious parasitic disease that affects humans and animals resulting in heavy health and economic burdens. Disturbance of redox equilibrium represents a classical challenge for both the host and the parasite during infections with either extracellular African or intracellular American trypanosomes species. This is in spite of existing detoxification mechanisms in both the host and the parasite for maintaining oxidative balance. However, oxidative stress still plays vital roles in the induction of numerous host-associated pathological damages such as anemia, hepatic and renal damages as well as cardiomyopathy while on the other hand, drugs that specifically induce oxidative stress to the parasite have been effective. Therefore, antioxidants have been deemed to play a role in modulating trypanosome infections. This review provides a current update on most of the studies conducted on the potential use of antioxidants as therapeutic agents against trypanosomes. The most frequently studied plant-derived phenolic antioxidants are resveratrol, cucurmin, gallic acid and quercetin while other antioxidants such as vitamins (A, C, E) and trace elements (selenium and iron) have been investigated. Some of the investigations monitored the direct trypanocidal or trypanostatic effects of the antioxidants while others studied the potentials of the antioxidants as adjuncts to trypanocidal drugs. So far, none of these approaches has sufficient data to allow a definite statement on the actual therapeutic potential of antioxidants in the treatment of clinical trypanosomiasis. Therefore, suggestions are made on the most therapeutically and clinically relevant role of antioxidants in trypanosome infections.
This study was designed to investigate the alteration of redox status by commonly used antimalarials in Nigeria. Drugs used were artemisinin, artesunate, chloroquine, coartem and quinine at the final concentrations of 0.5–8.0 mg/mL. Blood samples were collected from malarial patients and apparently healthy humans for comparison. Reduced glutathione, catalase, superoxide dismutase (SOD) activities, protein content and lipid peroxidation were determined. All drugs significantly (p < 0.05) increases the protein level relative to control in normal blood, whereas in the infected, a significant (p < 0.05) reduction was observed. In normal blood, the antimalarials dose dependently decreased (p < 0.05) SOD and catalase activities with significant (p < 0.05) increase in the infected. The level of glutathione in normal blood significantly (p < 0.05) increases as compared with control, whereas in the infected, similar observation was made except that the levels were less, relative to control sample. Malondialdehyde level significantly (p < 0.05) increases with increase in drugs concentration even though less than the level in the control with few exceptions. These effects were dose dependent and more pronounced in non-malarial conditions. Commonly used antimalarials might alter the redox status in both healthy and non-healthy subjects thereby inducing oxidative stress.
Recent advances in functional foods-based research have increasingly become an area of major interest because it affects human health and activities. Functional foods are classes of foods with health promoting and disease preventing properties in addition to multiple nutritional values and of such type is honey. Acacia honey is a type of honey produced by bees (Apis mellifera) fed on Acacia flowers, hence the name. This review focuses on the potential biological activities of Acacia honey which includes quality, antioxidant, immuno-modulatory, antiproliferative and neurological properties at in vitro and in vivo levels. Based on our review, Acacia honey used from various researches is of high purity, contains some bioactive compounds ranging from vitamins, phenolics, flavonoids and fatty acids. It's highly nutritional with strong antioxidant and immuno-modulatory potentials which may therefore be considered a potential candidate for both cancer prevention and treatment. Neurologically, it may be considered as a viable therapeutic agent in the management of Alzheimer's disease.
Background: Antimalarial drugs are medicines that are used to prevent or treat malaria effectively at different stages in the life cycle of the malarial parasites. In spite of this, a good number of these drugs have the potential to cause harm when they are misused or abused. Objective: This study was undertaken to evaluate the effects of commonly-used antimalarial drugs in the North Western region of Nigeria on haemolysis and DNA fragmentation in the blood of normal and malarial infected humans ex vivo. Method: The drugs used were artemisinine, artesunate, chloroquine, coartem and quinine (0.5-8.0 mg/ml). Haemolysis, haemoglobin status and DNA fragmentations were assayed for using standard procedures. Results: It was observed that all the drugs induced a remarkable dose-dependent haemolysis with more pronounced effects on apparently healthy humans. There was a significant (P < 0.05) decrease in the level of haemoglobin in normal blood samples when compared with control samples. Contrariwise, in the malaria-infected blood, the haemoglobin level significantly (P < 0.05) increased as compared with control. The drugs caused an exceptional significant (P < 0.05) induction of DNA fragmentation when compared with control. Conclusion: Commonly-used antimalarial drugs induced haemolysis and altered haemoglobin status which may spontaneously increases the cellular iron levels; a substrate for Fenton and Haber Weiss reactions, and eventually induces DNA fragmentation. Hence, adequate care should be taken during prescription with total avoidance for self medications and/or drugs abuse as a result of their adverse effects within the red blood cells and its immediate microenvironment.
Presentation made at 34th NSBMB Conference at Niger 2015 on EFFECTS OF COMBINED ADMINISTRATION OF RED PALM OIL (ELAESIS GUINEENSIS) AND AQUEOUS EXTRACT OF ROSELLE (HIBISCUS SABDARIFFA) CALYX ON HEPATIC AND RENAL FUNCTIONS OF T. brucei brucei INFECTED RATS.
Previous studies have suggested a possible connection between insulin resistance and chronic hyperglycemia with membrane sialic acid content. In this study, the effects of high (20 % ad libitum) fructose and glucose feeding on the sialic acid levels of some organs were investigated in rats. The blood glucose levels of the high fructose- and glucose-fed rats were consistently and significantly (P < 0.05) higher than the normal control throughout the experiment. Free serum sialic acid and total hepatic sialic acid levels were elevated in the high fructose- and glucose-fed rats compared to normal control, but only the data for the high glucose-fed group were significantly (P < 0.05) different from the normal control. Conversely, a significant (P < 0.05) decrease in the pancreatic sialic acid level was observed in high glucose-fed group compared to normal control. Also, the high fructose-fed rats had lower, but insignificant (P > 0.05), pancreatic sialic acid level than the normal control. On the other hand, high fructose and glucose feeding did not significantly (P > 0.05) affect the sialic acid levels of the skeletal muscle and heart, though a tendency to increase the sialic acid level was evident in the heart. In the kidney, the sialic acid level was significantly (P < 0.05) increased in both high fructose- and glucose-fed groups. It was concluded that the liver and kidney tend to stimulate sialic acid synthesis, while the pancreas downregulate sialic acids synthesis and/or promote sialic acid release from glycoconjugates. Also, these organs may contribute to high-serum sialic acid level observed during diabetes.
Objective: The aim was to determine the chemical constituents and antimicrobial activity of the hexane leaf extract of Anisopus mannii against a wide range of human pathogenic microorganisms. Methods: The chemical constituents of the hexane leaf extract was determined using gas chromatography-mass spectrometry (GC-MS) analysis; and the antimicrobial activity was evaluated on "standard strains", clinical susceptible and resistant bacterial and fungal isolates using the disc diffusion and broth microdilution methods. Results: GC-MS analysis of the hexane leaf extract revealed 32 compounds, representing 73.8% of the identified components. The major compounds were hexadecanoic acid, ethyl ester (34%), oxirane, hexadecyl- (11%) and 9, 12, 15-octadecatrienoic acid, ethyl ester, (Z, Z, Z) (9.6%). Results from the antimicrobial activity demonstrated higher inhibition zones against Bacillus cereus (29 mm), followed by Streptococcus pyogenes (28 mm). Other notable inhibitions were observed with Enterococcus faecalis (27 mm), Proteus vulgaris (26 mm) and MRSA (25 mm). The MIC values ranged from 0.625 mg/mL to 1.25 mg/mL while the MBC/MFC values ranged from 2.5 mg/mL to 5.0 mg/mL. Conclusion: These results support the traditional use of the plant and demonstrate the huge potential of A. mannii as a source of antimicrobial compounds.
Context: Diabetes mellitus is a chronic disease, and its incidence is tremendously increasing globally. Decreasing postprandial hyperglycemia by retarding glucose absorption through inhibiting carbohydrates digesting enzymes (α-amylase and α-glucosidase) is one of many approaches used for the management of this disease. Objectives: The leaf and root aqueous and ethanol extracts of Albizia antunesiana were investigated for α-amylase and α-glucosidase inhibitory and cytotoxic activity in vitro. Materials and methods: The α-amylase and α-glucosidase activities were measured in the presence of aqueous and ethanol extracts of the plant parts using starch and p-nitrophenyl-D-glucopyranoside as substrates respectively. Furthermore, cytotoxic effects of the extracts were investigated on HEK (human embryonic kidney) 293 cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. Results: The results showed that ethanolic root extract of A. antunesiana had mild α-amylase and strong α-glucosidase inhibitory activity with half-maximal inhibitory concentration values of 30.68 and 4.35 µg/mL, respectively. The aqueous root extract showed mild α-glucosidase but no α-amylase inhibitory activity. Cytotoxicity studies on the extracts using the MTT assay revealed that the ethanolic (leaf and root) extracts were relatively nontoxic at tested concentrations on the HEK 293 cell lines. However, the aqueous extracts (leaf and root) were cytotoxic at concentrations above 50 µg/mL. Conclusion: Data from this study suggest that the ethanolic root extract of A. antunesiana possess in vitro α-amylase and α-glucosidase inhibitory activities and are not cytotoxic at least in an in vitro condition.
Objective: To investigate the effects of combined administration of a low dose of a phenolicsrich fraction of Khaya senegalensis (PFKS) stem bark with α-tocopherol on Trypanosoma brucei brucei (T. brucei brucei) infection. Methods: Rats were divided into five groups of six animals, namely, normal control, uninfected but treated with PFKS and α-tocopherol, infected control, infected and treated with PFKS and α-tocopherol (ITTF) and infected treated with diminazine aceturate. Rats in infected control, ITTF and infected treated with diminazine aceturate were infected with T. brucei brucei while the animals in uninfected but treated with PFKS and α-tocopherol and ITTF were treated with a combination of PFKS (100 mg/kg body weight) and α-tocopherol (100 mg/kg body weight) for 8 days. At the end of the experiment, indices of anemia as well as hepatic and renal functions were analysed. Results: The combined treatment significantly (P < 0.05) retarded the proliferation of T. brucei brucei in the infected animals compared to the infected group but could not completely eliminate the parasites from the bloodstream of infected animals. Furthermore, the trypanosome-associated pathological changes such as anemia, hepatic and renal damages were significantly (P < 0.05) alleviated by the combination of PFKS and α-tocopherol. Conclusions: Combination of a low dose of PFKS stem bark and α-tocopherol could be a therapeutically active regimen against animal trypanosomiasis.
The study was intended to explore the antioxidant potential and phytochemical content of the ethanol and aqueous extracts of the leaf and root samples of Cissus comifolia (Baker) Splanch (Vitaceae) across a series of four in vitro models. The results showed that all the extracts had reducing power (Fe3+- Fe2+), and DPPH, hydroxyl and nitric oxide radical scavenging abilities to varying extents. However, the ethanol root extract had more potent antioxidant power in all the experimental models than other extracts and possessed a higher total phenol content of 136.1 +/- 6.7 mg/g. The GC-MS analysis of the aqueous and ethanol extracts of the roots indicated the presence of the common aromatic phenolic compounds, pyrogallol, resorcinol and catechol, a fatty acid, n-hexadecanoic acid and an aldehyde, vanillin. Data from this study suggest that both the leaves and roots of C. comifolia possessed anti-oxidative activities with the best anti-oxidant activity being exhibited by the ethanolic extract of the root. The antioxidant properties of the root extracts can be attributed to the phenolic compounds present in the extracts.
This study was conducted to investigate the effect of sodium arsenite and Acacia honey on acetylcholinesterase (AChE) activity and electrolytes in the brain and serum of Wistar rats. Male Wistar albino rats in four groups of five rats each were treated with distilled water, sodium arsenite (5 mg/kg body weight), Acacia honey (20% v/v), and sodium arsenite and Acacia honey, daily for one week. The sodium arsenite and Acacia honey significantly (P < 0.05) decreased AChE activity in the brain with the combined treatment being more potent. Furthermore, sodium arsenite and Acacia honey significantly (P < 0.05) decreased AChE activity in the serum. Strong correlation was observed between the sodium and calcium ion levels with acetylcholinesterase activity in the brain and serum. The gas chromatography mass spectrometry analysis of Acacia honey revealed the presence of a number of bioactive compounds such as phenolics, sugar derivatives, and fatty acids. These findings suggest that sodium arsenite and/or Acacia honey modulates acetylcholinesterase activities which may be explored in the management of Alzheimer's diseases but this might be counteracted by the hepatotoxicity induced by arsenics.
Abstract This study evaluated the in vitro antioxidative activity of Khaya senegalensis extracts and inhibitory effects of some solvent fractions on α-glucosidase and α-amylase activities. The stem bark, root and leaf samples of the plant were sequentially extracted with ethyl acetate, ethanol and water and then tested for antioxidative activity. Our findings revealed that the ethanolic extract of the root had the highest antioxidative activity. Solvent-solvent fractionation of the root ethanolic extract yielded a butanol fraction that showed higher antioxidative activity than other fractions. Furthermore, the butanol fraction had significantly higher (p < 0.05) α-glucosidase and α-amylase inhibitory activities with IC50 values of 2.89 ± 0.46 and 97.51 ± 5.72 μg mL-1, respectively. Enzyme kinetic studies indicated that the butanol fraction is a non-competitive inhibitor for α-glucosidase with an inhibition binding constant Ki of 1.30 μg mL-1 and a competitive inhibitor of α-amylase with a Ki of 7.50 μg mL-1. GC-MS analysis revealed that the butanol fraction contained two chromones, p-anilinophenol and 3-ethyl-5-(3- ethyl-(3H)-benzothiazol-2-ylidene)-2-(p-tolylvinylamino)- 4-thiazolidinone. Data obtained in the study suggest that the butanol fraction derived from the ethanolic extract of K. senegalensis root possessed excellent antioxidative as well as α-glucosidase and a-amylase inhibitory activities while chromones and/or p-anilinophenol could be the main bioactive compounds responsible for the observed activities.
Ethnopharmacological relevance: Khaya senegalensis A. Juss (Meliaceae) is commonly exploited for the traditional treatment of diabetes mellitus in Nigeria and Togo. The present study was conducted to examine the anti-diabetic activity of Khaya senegalensis butanol fraction (KSBF) of root ethanolic extract in a type 2 diabetes (T2D) model of rats. Materials and methods: T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight) and the animals were treated with 150 and 300 mg/kg body weight (BW) of the fraction for five days in a week. Relevant diabetes-related parameters were analyzed in all experimental animals. Results: The KSBF treatment, at 300 mg/kg BW, significantly (p<0.05) reduced blood glucose level, improved oral glucose tolerance ability and β-cell function (HOMA-β), decreased insulin resistance (HOMA-IR), stimulated hepatic glycogen synthesis, ameliorated serum lipids alterations and prevented hepatic and renal damages compared to untreated diabetic rats. Additionally, the fraction insignificantly (p>0.05) improved weight gain, decreased food and fluid intake, stimulated insulin secretion and lowered serum fructosamine concentrations compared to untreated diabetic rats. Conclusions: Data from this study suggests that orally administered KSBF, at 300 mg/kg BW, possess remarkable anti-type 2 diabetic activity and could ameliorate some diabetes-associated complications and hence can be considered as a source of potential anti-type 2 diabetic medicine.
The emergence of bone marrow micronucleated polychromatic erythrocytes (MN-PCE) in rats experimentally infected with Trypanosoma brucei brucei was examined in order to understand the bone marrow effects in trypanosomiasis infection. Bone marrow was collected for micronucleus assay while blood samples were collected from infected rat for hematological analysis. The results showed evidence of MN-PCE at 12.75±0.65 micronuclei/ 1000PCE and 9.60±2.95 micronuclei/1000PCE for rats infected for 21 days and 14 days respectively. The hematology examination revealed changes in packed cell volume, haemoglobin and red blood cells with concomitant increase in parasitemia. This study revealed that the generation of MN-PCE was induced by an acute infection of T. b. brucei in rats and this highlights an important phase in the pathogenesis of the disease that may indicate possible damage to genetic information.
Senna singueana is currently used in the traditional treatment of diabetes mellitus in Nigeria. The present study examined the anti-diabetic activity of the Senna singueana acetone fraction (SSAF) of stem bark in a type 2 diabetes (T2D) rat model. Crude extract of the Senna singueana stem bark was fractionated with various solvents and the acetone fraction was selected for in vivo studies based on the high α-glucosidase and α-amylase inhibitory activities. In the in vivo study, male Sprague-Dawley rats were induced with T2D and treated with the SSAF at 150 and 300mg/kg body weight. Several T2D-related parameters were measured in the study. After 4 weeks of intervention, non-fasting blood glucose concentrations were significantly decreased and the glucose tolerance ability was significantly improved in the SSAF treated groups compared to the diabetic control group. Serum insulin concentrations, pancreatic β-cell function (HOMA-β) and liver glycogen were significantly (P<0.05) increased while serum alanine transaminase, alkaline phosphatase and urea were significantly decreased in the SSAF treated diabetic rats compared to the diabetic control group. Though insignificantly (P>0.05), other T2D-induced abnormalities such as food and fluid intake, body weight change, serum lipids, serum fructosamine level and peripheral insulin resistance (HOMA-IR) were also partially ameliorated by the SSAF treatment. Data of this study suggest that orally administered SSAF could ameliorate most of the T2D-induced abnormalities in a T2D model of rats.
Diabetes mellitus is one of the major health problems in Africa. The conventional oral synthetic antidiabetic drugs available to manage the disease are costly and not readily affordable to the majority of the affected population. Interestingly, the continent is endowed with a tremendous number of medicinal plants that have been explored for their folkloric treatment of diabetes mellitus. Scientific investigations have validated the antidiabetic potentials of a number of these medicinal plants but there is no repository with information on these scientifically investigated plants as a guide for future research. In this review article, all of the in vivo antidiabetic studies conducted between January 2000 and July 2013 on African plants are systematically compiled with a closer look at some relevant plants from the continent's subregions. Plants of the Asteraceae and Lamiaceae families are the most investigated, and West Africa has the highest number of investigated plants. Although promising results were reported in many cases, unfortunately, only a few studies reported the partial characterization of bioactive principles and/or mechanisms of action. It is hoped that government agencies, pharmaceutical industries, and the scientific community will have a look at some of these plants for future research and, if possible, subsequent commercialization.
Oxidative damage is one of the most important pathological consequences of malarial infections. It affects vital organs of the body manifesting in changes such as splenomegaly, hepatomegaly, endothelial and cognitive damages. The currently used antimalarials often leave traces of these damages after therapy, as evident in memory impairment after cerebral malaria. Hence, some research investigations have focused attention on the use of antioxidants, alone or in combination with antimalarials, as a viable therapeutic strategy aimed at alleviating plasmodium-induced oxidative stress and its associated complications. However, the practical application of this approach often yields conflicting outcomes because some antimalarials specifically act via induction of oxidative stress. This article critically reviews most of the studies conducted on the potential role of antioxidant therapy in malarial infections. The most frequently investigated antioxidants are vitamins C and E, N-acetylcystein, folate and desferroxamine. Some of the investigations measured the effects of direct administration of the antioxidants on the plasmodium parasites while others performed an adjunctive therapy with standard antimalarials. The therapeutic application of each of the antioxidants in malaria management depends on the targeted aspect of malarial pathology. It is hoped that this article will provide an informed basis for future research activities on the therapeutic role of antioxidants on malarial pathogenesis.
The antioxidative activities of the ethanol and aqueous extracts of the leaf and root samples of Albizia antunesiana were determined across a series of four in vitro models. The results showed that all the extracts had reducing power (Fe(3+)- Fe2+), DPPH, hydroxyl and nitric oxide radical scavenging abilities. The ethanol root extract had more potent antioxidant power in all the experimental models and possesses a higher total phenol content of 216.6 +/- 6.7 mg/g. The GC-MS analysis of the aqueous and ethanol extracts of the roots and leaves indicated that several aromatic phenolic compounds, a coumarin and some common triterpenoids were present in these extracts. Data from this study suggest that the leaves and roots of Albizia antunesiana possessed antioxidative activities that varied depending on the solvents.
The anti-oxidative activities of sequentially extracted solvent fractions of different parts of P. biglobosa were evaluated in a series of in vitro assays. Our findings indicated that all extracts had electron donating and free radical scavenging activities. But the ethanol (EtOH) extracts from all the parts demonstrated more promising anti-oxidative effects in these experimental models. Apart from the aqueous extracts of the stem bark and leaves, all other extracts exhibited hydroxyl radical scavenging (HRS) activity but the ethyl acetate (EtOAc) extract of the stem bark and EtOH extracts of the root and leaves possessed more powerful HRS activity than other corresponding extracts in the parts. Further, nitric oxide (NO) inhibition activities were observed in all the extracts except the EtOAc extract of the stem bark which showed pro-oxidative activity. However, the EtOH extract of the stem bark and root as well as the EtOAc extract of the leaves displayed more potent anti-NO activity than other extracts in the parts. The GC-MS analysis of the EtOH extracts revealed that the most abundant phytochemicals are pyrogallol derivatives. Data from this study suggest that the EtOH extracts from different parts of P. biglobosa contained potent anti-oxidative agents and pyrogallol could be the main bioactive constituent.
The present study was conducted to investigate the anti-oxidative activities of different solvent extracts of Cassia singueana parts. Our results indicate that all the extracts have reducing power (Fe3+ --> Fe2+) and DPPH radical scavenging abilities. However, the ethyl acetate extract of the stem bark has the highest total reducing power whilst the ethanol extract of the stem bark has more potent free radical scavenging activity than all the other extracts. The ethyl acetate extract of the stem bark exhibited more powerful hydroxyl radical scavenging activity than other extracts whilst the aqueous extract of the leaves displayed more potent nitric oxide inhibition activity than other extracts. The GC-MS analysis of the ethyl acetate extract of the stem bark and the ethanol extract of the root and leaves indicated that several aromatic compounds, including phenolics, fatty acids, amino acids and triterpenoids were present in these extracts. Data from this study suggest that the parts of C. singueana possessed anti-oxidative activities and can be used as a potential alternative medicine for oxidative stress related non-communicable chronic diseases. Further experimental and clinical studies in this regard are warranted.
To examine the in vitro and in vivo anti-Trypanosoma evansi (T. evansi ) activity of saponins-rich fraction of Calotropis procera (cpsf) leaves as well as the effect of the fraction on the parasite-induced anemia. A 60-minutes time course experiment was conducted with various concentrations of the fraction using a 96-well microtiter plate technique, and subsequently used to treat experimentally T. evansi infected rats at 100 and 200 mg/kg body weight. Index of anemia was analyzed in all animals during the experiment. The cpsf did not demonstrate an in vitro antitrypanosomal activity. Further, the cpsf treatments did not significantly (P>0.05) keep the parasites lower than the infected untreated groups. At the end of the experiment, all T. evansi infected rats developed anemia whose severity was not significantly (P>0.05) ameliorated by the cpsf treatment. It was concluded that saponins derived from Calotropis procera leaves could not elicit in vitro and in vivo activities against T. evansi.
Context: The stem bark of Khaya senegalensis A. Juss (Meliaceae) is currently used for the treatment of trypanosomiasis by traditional practitioners in Nigeria. Objectives: The present study investigated the anti-Trypanosoma brucei brucei activity of phenolics-rich fraction of K. senegalensis (pfks) and its ameliorative effects on trypanosome-induced pathological changes. Materials and methods: The fraction was initially analyzed by gas chromatography-mass spectrometry (GC-MS). A 60 min time course experiment was conducted with various concentrations of the fraction using a 96-well microtiter plate technique and was further used to treat T. brucei infected rats at 100, 200 and 300 mg/kg body weight (BW). Indices of anemia as well as hepatic and renal functions were analyzed in all experimental animals at the end of the experiment. Results: The GC-MS analysis of the pfks revealed that the most abundant phytochemicals are phloroglucinol (40.56%) and 3,4-(dihydroxyphenyl) acetic acid (41.76%). The fraction showed a concentration dependent in vitro antitrypanosomal activity. Interestingly, the fraction completely eliminated the parasites from the bloodstream of infected rats without relapse during the experimental period at the dose of 300 mg/kg BW and also kept the parasites consistently lower at 100 and 200 mg/kg BW than that was recorded in the untreated infected rats. Furthermore, the severity of T. brucei-induced anemia and hepatic damage was significantly (p < 0.05) ameliorated in the 300 mg/kg BW treatment group whereas the parasite-induced renal damage was significantly (p < 0.05) ameliorated in all treatment groups. Conclusion: Data from this study may suggest that phenolics play an important role in the antitrypanosomal activity of K. senegalensis.
Antioxidants activities from plants sources have attracted a wide range of interest across the world in recent times. This is due to growing concern for safe and alternative sources of antioxidants. The free radical scavenging activity using 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), reducing power assay, total antioxidant capacity of the phosphomolybdenum method and the total phenolics content using the Folin-Ciocalteu reagent were carried out on the acetone, n-butanol and methanol root extracts of Anchomanes dif-formis. The results of the total phenolics content expressed in mg/100 g of gallic acid equivalent (GAE) showed that the n-butanol extract has significantly (p < 0.05) higher phenolics content (381 +/- 1.13) than the methanol and acetone extracts. All the extracts displayed strong concentration dependent radical scavenging activity. It was also observed that the n-butanol extract showed higher activity of 70.87% and 78.59% at low concentrations of 31.25 microg/mL and 62.5 microg/mL, respectively, than methanol and acetone extracts. The results also showed that the n-butanol extract has strongest reducing ability which is comparable to that of gallic acid at all the concentrations tested. Phytochemical screening on the extracts revealed the presence of flavonoids, saponins, and tannins. The results suggest that n-butanol extract of the plant is very rich in antioxidant compounds worthy of further investigations.
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