Background: Cancer remains one of the leading causalities of several morbidity and mortality with... more Background: Cancer remains one of the leading causalities of several morbidity and mortality with negative impact on global economy due to low workforce and management/treatment cost. A number of conventional therapies have been explored in the management/treatment of cancer including chemotherapeutic intervention, radiotherapy, and surgery. Among these treatment modalities, chemotherapy remains the most popular first line of intervention in management/treatment of cancer, and natural products have been implicated as the main source of antineoplastic agents with phenomenal efficacy. However, current antineoplastic agents suffer from lack of selectivity and specificity necessitating the need for further research in the search for novel anticancer drug molecules. Methods: In this present study, the anticancer activity of Hoslundia opposita leaves extracts were tested against a number of cell lines including human hepatoma cell line (HepG2), human breast cancer cell lines (MDA-MB-231), intestinal epithelial cell lines (Caco-2), and human keratinocyte HACAT cell lines. A bio-guided fractionation assay and the structural elucidation of the pure isolate (hoslundin) was conducted by 1D and 2 D NMR spectroscopy. The cell viability, colony formation, and apoptotic activities were investigated using MTT assay, clonogenic assay, and caspase -3 and -7 kits respectively. Flow cytometry was employed in assessing the altered cell cycle expression. The production of the intracellular reactive oxygen species (ROS) levels and the reduction of the mitochondrial membrane potential (MMP) was determined at the cellular level using fluorescent probe dyes dihydro-fluorescin diacetate (DCFH-DA) and tetramethylrhodamin (TMRE), respectively. Results: The H. opposita fractions and its pure isolate (hoslundin) demonstrated a potent cytocidal activity against the tumorigenic cells (HepG2, MDA-MB-231, Caco-2) at concentration ranging from 25 to 100 µg/mL. The inhibition of the colony formation was significantly observed in HepG2 cell lines. More so, the cellular viability of the normal cells (HaCaT) was relatively unchanged in the presence of H. opposita fractions and its isolate proving the selectivity of the compounds towards tumourigenic cells. The H. opposita fractions and hoslundin exerted their anticancer activity via cell cycle arrest with the accumulation of the DNA content at the S-phase, activation
Immersive technologies are redefining ways of interacting with 3D objects and their environments.... more Immersive technologies are redefining ways of interacting with 3D objects and their environments. Moreover, efforts in blended learning have presented several advantages of incorporating educational technology into the learning space. The advances in educational technology have in turn helped to widen the choice of different pedagogies for improving learner engagement and levels of understanding. However, there is limited research in anatomy education that has considered the use and adoption of immersive technologies for the musculoskeletal system, despite its immense advantage. This research presents a practical immersive anatomy education system (coined Anat_Hub) developed using the agile scrum and participatory design method at a selected tertiary institution in Cape Town, South Africa, which promotes learner engagement through an asynchronous technological means using augmented reality (AR). The aim of the study was to develop an immersive AR mobile application that will assist ...
Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Abstract Multitarget directed ligands (MTDLs) are emerging as promising treatment options for Alz... more Abstract Multitarget directed ligands (MTDLs) are emerging as promising treatment options for Alzheimer’s disease (AD). Coumarin derivatives serve as a good starting point for designing MTDLs due to their inherent inhibition of monoamine oxidase (MAO) and cholinesterase enzymes, which are complicit in AD’s complex pathophysiology. A preliminary series of 3,7-substituted coumarin derivatives were synthesised and evaluated for enzyme inhibitory activity, cytotoxicity as well as neuroprotective ability. The results indicated that the compounds are weak cholinesterase inhibitors with five compounds demonstrating relatively potent inhibition and selectivity towards MAO-B with IC50 values between 0.014 and 0.498 hx00B5;µM. Significant neuroprotective effects towards MPP+-compromised SH-SY5Y neuroblastoma cells were also observed, with no inherent cytotoxicity at 10 µM for all compounds. The overall results demonstrated that substitution of the phenylethyloxy moiety at the 7-position imparted superior general activity to the derivatives, with the propargylamine substitution at the 3-position, in particular, displaying the best MAO-B selectivity and neuroprotection.
In a bid to test the wound healing effect of a crude methanolic extract of Ageratum conyzoides (L... more In a bid to test the wound healing effect of a crude methanolic extract of Ageratum conyzoides (Linn.), 20 animals were divided into two groups of ten animals each representing control and experimental groups. Each animal had a 2cm x 2cm area of skin on the right dorsolateral flank area marked and excised. The resulting area of skin wound in the experimental group was dressed with crude methanolic extract of Ageratum conyzoides at a five daily interval while the animals in the control group were dressed with normal saline at the same interval. The wound area was measured at the tenth post-operative day for animals in both groups and the percentage wound contraction calculated. Sample of granulation tissues and end scar obtained from these animals and prepared by routine paraffin wax method. Fibroblast and blood vessel counts were determined in both groups. The result showed a significant increase in the percentage wound contraction at day 10 in the experimental group compared with the control (82.3 ± 1.6 % vs 55.0 ± 4.2 %), P < 0.05. The wound of animals in both groups showed excellent granulation tissue formation and minimal signs of wound infection. There was a significant reduction in the mean fibroblast count in the experimental group compared with the control (44.2 ± 5.8/ high power field vs 90.2 ± 17. 4 / high power field),P < 0.05. The exact significance of this cannot however be determined. There was no significance difference in the vessel count. It was concluded that extract of Ageratum conyzoides has a better wound healing enhancing action compared with normal saline treated controls. This effect may be due to the antimicrobial properties of Ageratum conyzoides.
Open and rearranged norbornane derived polycyclic cage molecules as potential neuroprotective age... more Open and rearranged norbornane derived polycyclic cage molecules as potential neuroprotective agents through attenuation of MPP + -and calcium overload-induced excitotoxicity in neuroblastoma SH-SY5Y cells,
Malignant primary brain tumours are reported to be the leading cause of death from solid tumours ... more Malignant primary brain tumours are reported to be the leading cause of death from solid tumours in children and the third leading cause of death from cancer in adolescents and adults. Current treatment options include surgery, radiation and chemotherapy. Despite these treatment options, patient survival still remains poor. The Amaryllidaceae family contains alkaloids which have shown several biological activities including the treatment of Alzheimer's disease. This study investigates the cytotoxic activity of the methanolic extracts of fourteen plants belonging to the Amaryllidaceae family in brain tumour cell lines. The MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide) cell viability assay was used to determine the effects of plant extracts on cell viability while routine antioxidant assays were conducted to determine the antioxidant activities of the extracts. Results showed that of the fourteen extracts, five (Cyrtanthus breviflorus, Amaryllis belladonna, Crinum variabile, Haemanthus pubescens, Nerine filifolia) showed cytotoxicity in all the cell lines tested with IC 50 values under 100 mg/mL. Six extracts (Crinum moorei, Clivia miniata, Haemanthus amarylloides, Crossyne guttata, Nerine humilis, and Ammocharis longifolia) showed varying levels of cytotoxicity in the cell lines tested and were unable to induce 50% reduction in cell viability across the cell lines tested at the highest concentration of 100 mg/mL. Furthermore, three plant extracts (Brunsvigia bosmaniae, Boophone disticha, Strumaria truncata) had minimal or no cytotoxic effects on all cell lines tested when compared to control. The extracts also showed varying degrees of antioxidant activity but were not as potent as the positive control. Findings from this study suggest that species of the Amaryllidaceae family may be useful sources of phytochemicals for the treatment of central nervous system cancers and should be further explored in animal models of central nervous system (CNS) and other cancer types.
Many plant-derived bioactive compounds such as rutin are reportedly effective in attenuating neur... more Many plant-derived bioactive compounds such as rutin are reportedly effective in attenuating neuronal death in most neurodegenerative disorders. Parkinson's disease (PD) is characterized by the gradual degeneration of dopaminergic neurons in the substantia nigra of the midbrain, and has previously been modelled in-vitro through the specific neurotoxic activity of 1-methyl-4-phenylpyridinium (MPP+) on dopaminergic neurons. Rutin is a bioflavonoid with multiple pharmacological effects, and this study investigated the neuroprotective effects of rutin in the human dopaminergic SH-SY5Y cell line using the neurotoxin MPP+. SH-SY5Y cells pretreated with rutin, were exposed to MPP+ and evaluated for cell viability, nitric oxide (NO), reactive oxygen species (ROS) and antioxidant enzymes activities. In addition, western blot techniques were used to determine the protein expression levels of γH2AX and COX-2. Rutin significantly attenuated MPP+-induced loss of cell viability, mitigated ROS and NO production and inhibited the disruption of antioxidant enzymes activity. It was also observed that rutin significantly reduced protein expression levels of γH2AX and COX-2 in SH-SY5Y cells treated with MPP+. Taken together, findings from this study tend to suggest that rutin is a promising neuroprotective compound for the treatment of PD through its effects on some of the mechanisms that characterize this neurodegenerative disease.
Evidence-Based Complementary and Alternative Medicine, 2020
In the article titled "Antiproliferative and Apoptosis Induction Potential of the Methanolic Leaf... more In the article titled "Antiproliferative and Apoptosis Induction Potential of the Methanolic Leaf Extract of Holarrhena floribunda (G. Don)", there was figure duplication . As raised on PubPeer [2], Figure KMST-6 control and KMST-6 200 μg/mL are the same. e authors could not find the original images and confirmed that the photomicrographs were directly copied into a Microsoft Word document as their record of the analysis. One or both of the photomicrographs was used in error and they should be disregarded. However, the raw data (Supplementary Materials) reflect significant differences between KMST-6 colony counts for the control and the 200 μg/ml treatment, supporting the results in the article.
The anti-cancer activities of many fermented foods and beverages are now scientifically establish... more The anti-cancer activities of many fermented foods and beverages are now scientifically established. Ogiri-egusi is a condiment prepared from fermentation of Citrullus vulgaris (melon) seeds and consumed in many countries of West Africa. Its anti-oxidative and anti-hyperlipidaemic properties have been reported. This study investigated the anti-cancer activities of the aqueous and methanolic extracts from ogiri-egusi. Cytotoxicity was investigated using the MTT and colonyformation inhibition assays while flow-cytometer based Apopercentage assay was used to quantify apoptosis in extractstreated cervical and liver cancer and normal human fibroblast cells. The inhibitory concentration responsible for killing 50% of cells after 24 h by the aqueous extract in KMST-6, HeLa, and Hep-G2 cells were estimated at 1.610, 1.020, and 1.507 mg/mL respectively. While these values reduced with increasing incubation time in cancer cells it increased in the non-cancer cell. Furthermore, the extract significantly induced apoptosis in HeLa (97 ± 0.18%) and Hep-G2 (73 ± 6.73%) cells. These findings were corroborated by cells morphologic presentations and inhibition of colony formation assay. These findings suggest that the aqueous extract from fermented Citrullus vulgaris seeds might be a nutraceutical with potential anti-cancer properties.
Glioblastoma remains the most malignant of all primary adult brain tumours with poor patient surv... more Glioblastoma remains the most malignant of all primary adult brain tumours with poor patient survival and limited treatment options. This study adopts a drug repurposing approach by investigating the anti-cancer activity of a derivative of the antipsychotic drug phenothiazine (DS00329) in malignant U251 and U87 glioblastoma cells. Results from MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and clonogenic assays showed that DS00329 inhibited short-term glioblastoma cell viability and long-term survival while sparing non-cancerous cells. Western blot analysis with an antibody to γH2AX showed that DS00329 induced DNA damage and flow cytometry and western blotting confirmed that it triggered a G1 cell cycle arrest which correlated with decreased levels in Cyclin A, Cyclin B, Cyclin D1 and cyclin dependent kinase 2 and an increase in levels of the cyclin dependent kinase inhibitor p21. DS00329 treated glioblastoma cells exhibited morphological and molecular markers typical of apoptotic cells such as membrane blebbing and cell shrinkage and an increase in levels of cleaved PARP. Flow cytometry with annexin V-FITC/propidium iodide staining confirmed that DS00329 induced apoptotic cell death in glioblastoma cells. We also show that DS00329 treatment of glioblastoma cells led to an increase in the autophagosome marker LC3-II and autophagy inhibition studies using bafilomycin A1 and wortmannin, showed that DS00329-induced-autophagy was a pro-death mechanism. Furthermore, DS00329 treatment of glioblastoma cells inhibited the phosphatidylinositol 3′-kinase/Akt cell survival pathway. Our findings suggest that DS00329 may be an effective treatment for glioblastoma and provide a rationale for further exploration and validation of the use of phenothiazines and their derivatives in the treatment of glioblastoma. Keywords Drug repurposing • Phenothiazines • Glioblastoma • Apoptosis • Autophagy Abbreviations PTZ Phenothiazine MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide γH2AX Phosphorylated H2A histone family member X CDK2 Cyclin-dependent kinase 2 PARP Poly (ADP-ribose) polymerase FITC Fluorescein isothiocyanate (FITC) LC3 Microtubule-associated protein light chain 3 FACS Fluorescence-activated cell sorting AVO Acidic vesicular organelles PI3K/Akt Phosphatidylinositol 3′ kinase/Akt MAPK Mitogen activated protein kinase ATM Ataxia-telangiectasia mutated * S.
Background: The plant Holarrhena floribunda (H. floribunda; G. Don) is indigenous to sub-Saharan ... more Background: The plant Holarrhena floribunda (H. floribunda; G. Don) is indigenous to sub-Saharan Africa and is traditionally used to treat several ailments. The present study was carried out to isolate and characterize bioactive compounds with anti-proliferative activity present in H. floribunda extracts. Methods: Compounds were isolated from H. floribunda using the bioassay-guided fractionation technique of repeated column chromatography and the step-wise application of the MTT reduction assay to assess antiproliferative bioactivity. The structures of the compounds were identified mainly using NMR. The effects of the isolated compounds on the viability, cell cycle and proliferation of human cancer cell lines (MCF-7, HeLa and HT-29) as well as the non-cancerous human fibroblast cell line (KMST-6) were investigated. Results: Bioassay-guided fractionation yielded two steroidal alkaloids: holamine (1) and funtumine (2). The MTT reduction assay shows that both compounds exhibited selective dose-dependent cytotoxicity against the cancer cell lines studied. The isolated compounds induced cell cycle arrest at the G 0 /G 1 and G 2 /M phases in the cancer cell lines with significant reduction in DNA synthesis. The results obtained show that the cancer cells (MCF-7, HeLa and HT-29) used in this study were more sensitive to the isolated compounds compared to the noncancerous fibroblast cells (KMST-6). The ability of the isolated compounds to cause cell cycle arrest and reduce DNA synthesis raises hopes for their possible development and use as potent anticancer drugs. However, more mechanistic studies need to be done for complete validation of the efficacy of the two compounds.
Many natural products and medicinal plants have been tested experimentally for validation of thei... more Many natural products and medicinal plants have been tested experimentally for validation of their reported folkloric efficacies. South Africa has abundant plant biodiversity and medicinal plants are still widely used in most parts of the country for the treatment of common neurodegenerative disorders (NDDs). However, very few studies have reported on the validation of South African medicinal plants (SAMPs) used in traditional, complementary and alternative medicine (TCAM) for the treatment of NDDs. Extensive testing provides the basis for clinical trials which progressively lead to the development of affordable indigenous and readily available products for preventing or treating NDD including Parkinson's disease (PD), one of the most common central nervous system (CNS) disorders among the elderly often characterized by the progressive loss of dopaminergic neurons (DNs) or dopamine-producing cells in the substantia nigra of the midbrain. In this study, several databases were searched to identify active compounds in SAMPs known to potentially protect neurons from progressive damage as seen in most NDDs. Our search results showed many commonly used SAMPs and their possible mechanisms of action including prevention of neuronal death by inhibition of Caspase-3 activation, MAO-B enzyme inhibition as well as restoration of glutathione content in cells. Most of the observed effects relate to the protection of DNs from degeneration, indicating the potential use of these compounds as antiparkinsonian agents. This review article therefore identifies and presents research gaps on how indigenous SAMPs could be studied more extensively for their chemical constituents and bioactivity against age-related NDDs such as PD.
The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challen... more The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challenges in the design of a single molecule that may ultimately prevent the progression of these disorders in affected patients. In this article, we report on twelve novel polycyclic amine cage derivatives, synthesized with or without a propargylamine function, designed to possess inherent multifunctional neuroprotective activity. The MTT cytotoxicity assay results showed the SH-SY5Y human neuroblastoma cells to be viable with the twelve compounds, particularly at concentrations less than 10 µM. The compounds also showed significant neuroprotective activity, ranging from 31% to 66% at 1 µM, when assayed on SH-SY5Y human neuroblastoma cells in which neurodegeneration was induced by MPP + . Calcium regulation assays conducted on the same cell line showed the compounds to be significant VGCC blockers with activity ranging from 26.6% to 51.3% at 10 µM; as well as significant NMDAr antagonists, with compound 5 showing the best activity of 88.3% at 10 µM. When assayed on human MAO isoenzymes, most of the compounds showed significant inhibitory activity, with compound 5 showing the best activity (MAO-B: IC 50 = 1.70 µM). Generally, the compounds were about 3 -52 times more selective to the MAO-B isoenzyme than the MAO-A isoenzyme. Based on the time-dependency studies conducted, the compounds can be defined as reversible MAO inhibitors. Several structure activity relationships were derived from the various assays conducted, and the compounds' possible putative binding modes within the MAO-B enzyme cavity were assessed in silico.
EUPHORBIA HIRTAISAPLANTUSEDIN TRADItional medicine for a variety of diseases, such as cough, asth... more EUPHORBIA HIRTAISAPLANTUSEDIN TRADItional medicine for a variety of diseases, such as cough, asthma, colic dysentery and genito-urinary infection. This plant, belonging to the family Euphorbiaceae, is also known as the Australian asthma herb or Queensland asthma weed, and is not toxic whentaken in typical dosages. In SouthAfrica, it is commonly used for asthma, which is one of the most common respiratory complaints. Although corticosteroids are considered the best means of defence against this debilitating illness, many people, especially in poor countries, rely on herbal remedies for its treatment. We discuss recently published results to assess the effect of the plant using the BALB/c murine asthma model. We also review the different compounds found in plant extracts, in an attempt to understand the reason for its anti-inflammatory properties. We conclude that the flavonoids quercitrin (converted to quercetin in the alimentary canal) and myricitrin, as well as the sterols 24-methy...
African journal of medicine and medical sciences, 2005
The teratogenic effect of maternal cyanide consumption on the gross morphology of the post-natal ... more The teratogenic effect of maternal cyanide consumption on the gross morphology of the post-natal phase of the developing rat cerebellum was studied. Twenty pregnant female rats weighing between 170 g and 190 g were separated into control and experimental groups. The control animals were fed a standard diet of mice cubes, while the experimental animals were fed 500 ppm potassium cyanide, mixed with the standard diet. The diets were fed to the animals and their litters in separate cages and water provided ad libitum during gestation and to the offspring after birth. After birth, the offspring (five per group) of days 1, 9, 14, 21, 28 and 50 were weighed, killed by cervical dislocation and the gross parameters studied. In the experimental animals, no significant differences were observed in the studied parameters between the control and experimental animals on day 1. A significant reduction in body weight was observed on day 14 (P < 0.05). The brain weight was significantly reduced ...
African journal of medicine and medical sciences, 2003
The present study investigates the wound healing properties of methanolic extracts of Ageratum co... more The present study investigates the wound healing properties of methanolic extracts of Ageratum conyzoides leaves compared with those of honey. Thirty Wistar rats were randomized into 3 groups of 10 animals each. They were fed with standard rat cubes and Tap water weighed and acclimatized to laboratory conditions for one week. Under anesthesia, each animal had the skin of its dorsolateral flank shaved after which an area of the skin was excised. On achieving haemostasis, the wounds were packed with gauze soaked in the appropriate dressing for each group. Measurement of wound size, and wound biopsies were taken on the 10th day post-wound creation. Together with healed wound samples, these were processed for histology. Fibroblast and blood vessel densities per unit area of wound were determined for the healed wound samples. Histologically, the day 10 Ageratum sections showed fewer inflammatory cells compared with similar honey and Control sections. Also, healed scar sections of wounds ...
tional medicine for a variety of diseases, such as cough, asthma, colic dysentery and genito-urin... more tional medicine for a variety of diseases, such as cough, asthma, colic dysentery and genito-urinary infection. This plant, belonging to the family Euphorbiaceae, is also known as the Australian asthma herb or Queensland asthma weed, and is not toxic when taken in typical dosages. In South Africa, it is commonly used for asthma, which is one of the most common respiratory complaints. Although corticosteroids are considered the best means of defence against this debilitating illness, many people, especially in poor countries, rely on herbal remedies for its treatment. We discuss recently published results to assess the effect of the plant using the BALB/c murine asthma model. We also review the different compounds found in plant extracts, in an attempt to understand the reason for its anti-inflammatory properties. We conclude that the flavonoids quercitrin (converted to quercetin in the alimentary canal) and myricitrin, as well as the sterols 24-methylene-cycloartenol and -sitosterol, exert noteworthy and dose-dependent anti-inflammatory activity. The triterpene β-amyrin also seems to exert a similar anti-inflammatory activity. Tannins and tannic acid derivatives, also present in the plant, have antiseptic effects and the two triterpenoids, taraxerone (EH-1) and 11α, 12α-oxidotaraxerol (EH-2), in E. hirta demonstrate antibacterial and antifungal properties. The effectiveness of E. hirta in treating asthma may lie predominantly in the synergistic relationships between the flavonoids, sterols and triterpenoids.
Platelets and fibrin play an important role in the coagulation process, where they are involved i... more Platelets and fibrin play an important role in the coagulation process, where they are involved in the maintenance of hemostasis. Fibrin dysfunction is associated with the development of vascular complications, while proneness to the formation of tight and rigid fibrin networks is independently associated with thrombotic disease. Here we investigate the ultrastructure of human, rabbit, and mouse platelets and fibrin networks, using the scanning electron microscope. Human and rabbit fibrin and platelets, with regards to morphology as well as size of major and minor fibers compare well with each other. However, mouse fibers are much thinner and form a flimsy branching network. Platelet aggregate morphology of all three species compare well with each other. We conclude that rabbit platelet and fibrin networks could be used successfully when studying the effect of pharmaceutical products in preclinical trials, when looking at the effects of these products on morphology and ultrastructur...
Background: Cancer remains one of the leading causalities of several morbidity and mortality with... more Background: Cancer remains one of the leading causalities of several morbidity and mortality with negative impact on global economy due to low workforce and management/treatment cost. A number of conventional therapies have been explored in the management/treatment of cancer including chemotherapeutic intervention, radiotherapy, and surgery. Among these treatment modalities, chemotherapy remains the most popular first line of intervention in management/treatment of cancer, and natural products have been implicated as the main source of antineoplastic agents with phenomenal efficacy. However, current antineoplastic agents suffer from lack of selectivity and specificity necessitating the need for further research in the search for novel anticancer drug molecules. Methods: In this present study, the anticancer activity of Hoslundia opposita leaves extracts were tested against a number of cell lines including human hepatoma cell line (HepG2), human breast cancer cell lines (MDA-MB-231), intestinal epithelial cell lines (Caco-2), and human keratinocyte HACAT cell lines. A bio-guided fractionation assay and the structural elucidation of the pure isolate (hoslundin) was conducted by 1D and 2 D NMR spectroscopy. The cell viability, colony formation, and apoptotic activities were investigated using MTT assay, clonogenic assay, and caspase -3 and -7 kits respectively. Flow cytometry was employed in assessing the altered cell cycle expression. The production of the intracellular reactive oxygen species (ROS) levels and the reduction of the mitochondrial membrane potential (MMP) was determined at the cellular level using fluorescent probe dyes dihydro-fluorescin diacetate (DCFH-DA) and tetramethylrhodamin (TMRE), respectively. Results: The H. opposita fractions and its pure isolate (hoslundin) demonstrated a potent cytocidal activity against the tumorigenic cells (HepG2, MDA-MB-231, Caco-2) at concentration ranging from 25 to 100 µg/mL. The inhibition of the colony formation was significantly observed in HepG2 cell lines. More so, the cellular viability of the normal cells (HaCaT) was relatively unchanged in the presence of H. opposita fractions and its isolate proving the selectivity of the compounds towards tumourigenic cells. The H. opposita fractions and hoslundin exerted their anticancer activity via cell cycle arrest with the accumulation of the DNA content at the S-phase, activation
Immersive technologies are redefining ways of interacting with 3D objects and their environments.... more Immersive technologies are redefining ways of interacting with 3D objects and their environments. Moreover, efforts in blended learning have presented several advantages of incorporating educational technology into the learning space. The advances in educational technology have in turn helped to widen the choice of different pedagogies for improving learner engagement and levels of understanding. However, there is limited research in anatomy education that has considered the use and adoption of immersive technologies for the musculoskeletal system, despite its immense advantage. This research presents a practical immersive anatomy education system (coined Anat_Hub) developed using the agile scrum and participatory design method at a selected tertiary institution in Cape Town, South Africa, which promotes learner engagement through an asynchronous technological means using augmented reality (AR). The aim of the study was to develop an immersive AR mobile application that will assist ...
Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Abstract Multitarget directed ligands (MTDLs) are emerging as promising treatment options for Alz... more Abstract Multitarget directed ligands (MTDLs) are emerging as promising treatment options for Alzheimer’s disease (AD). Coumarin derivatives serve as a good starting point for designing MTDLs due to their inherent inhibition of monoamine oxidase (MAO) and cholinesterase enzymes, which are complicit in AD’s complex pathophysiology. A preliminary series of 3,7-substituted coumarin derivatives were synthesised and evaluated for enzyme inhibitory activity, cytotoxicity as well as neuroprotective ability. The results indicated that the compounds are weak cholinesterase inhibitors with five compounds demonstrating relatively potent inhibition and selectivity towards MAO-B with IC50 values between 0.014 and 0.498 hx00B5;µM. Significant neuroprotective effects towards MPP+-compromised SH-SY5Y neuroblastoma cells were also observed, with no inherent cytotoxicity at 10 µM for all compounds. The overall results demonstrated that substitution of the phenylethyloxy moiety at the 7-position imparted superior general activity to the derivatives, with the propargylamine substitution at the 3-position, in particular, displaying the best MAO-B selectivity and neuroprotection.
In a bid to test the wound healing effect of a crude methanolic extract of Ageratum conyzoides (L... more In a bid to test the wound healing effect of a crude methanolic extract of Ageratum conyzoides (Linn.), 20 animals were divided into two groups of ten animals each representing control and experimental groups. Each animal had a 2cm x 2cm area of skin on the right dorsolateral flank area marked and excised. The resulting area of skin wound in the experimental group was dressed with crude methanolic extract of Ageratum conyzoides at a five daily interval while the animals in the control group were dressed with normal saline at the same interval. The wound area was measured at the tenth post-operative day for animals in both groups and the percentage wound contraction calculated. Sample of granulation tissues and end scar obtained from these animals and prepared by routine paraffin wax method. Fibroblast and blood vessel counts were determined in both groups. The result showed a significant increase in the percentage wound contraction at day 10 in the experimental group compared with the control (82.3 ± 1.6 % vs 55.0 ± 4.2 %), P < 0.05. The wound of animals in both groups showed excellent granulation tissue formation and minimal signs of wound infection. There was a significant reduction in the mean fibroblast count in the experimental group compared with the control (44.2 ± 5.8/ high power field vs 90.2 ± 17. 4 / high power field),P < 0.05. The exact significance of this cannot however be determined. There was no significance difference in the vessel count. It was concluded that extract of Ageratum conyzoides has a better wound healing enhancing action compared with normal saline treated controls. This effect may be due to the antimicrobial properties of Ageratum conyzoides.
Open and rearranged norbornane derived polycyclic cage molecules as potential neuroprotective age... more Open and rearranged norbornane derived polycyclic cage molecules as potential neuroprotective agents through attenuation of MPP + -and calcium overload-induced excitotoxicity in neuroblastoma SH-SY5Y cells,
Malignant primary brain tumours are reported to be the leading cause of death from solid tumours ... more Malignant primary brain tumours are reported to be the leading cause of death from solid tumours in children and the third leading cause of death from cancer in adolescents and adults. Current treatment options include surgery, radiation and chemotherapy. Despite these treatment options, patient survival still remains poor. The Amaryllidaceae family contains alkaloids which have shown several biological activities including the treatment of Alzheimer's disease. This study investigates the cytotoxic activity of the methanolic extracts of fourteen plants belonging to the Amaryllidaceae family in brain tumour cell lines. The MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide) cell viability assay was used to determine the effects of plant extracts on cell viability while routine antioxidant assays were conducted to determine the antioxidant activities of the extracts. Results showed that of the fourteen extracts, five (Cyrtanthus breviflorus, Amaryllis belladonna, Crinum variabile, Haemanthus pubescens, Nerine filifolia) showed cytotoxicity in all the cell lines tested with IC 50 values under 100 mg/mL. Six extracts (Crinum moorei, Clivia miniata, Haemanthus amarylloides, Crossyne guttata, Nerine humilis, and Ammocharis longifolia) showed varying levels of cytotoxicity in the cell lines tested and were unable to induce 50% reduction in cell viability across the cell lines tested at the highest concentration of 100 mg/mL. Furthermore, three plant extracts (Brunsvigia bosmaniae, Boophone disticha, Strumaria truncata) had minimal or no cytotoxic effects on all cell lines tested when compared to control. The extracts also showed varying degrees of antioxidant activity but were not as potent as the positive control. Findings from this study suggest that species of the Amaryllidaceae family may be useful sources of phytochemicals for the treatment of central nervous system cancers and should be further explored in animal models of central nervous system (CNS) and other cancer types.
Many plant-derived bioactive compounds such as rutin are reportedly effective in attenuating neur... more Many plant-derived bioactive compounds such as rutin are reportedly effective in attenuating neuronal death in most neurodegenerative disorders. Parkinson's disease (PD) is characterized by the gradual degeneration of dopaminergic neurons in the substantia nigra of the midbrain, and has previously been modelled in-vitro through the specific neurotoxic activity of 1-methyl-4-phenylpyridinium (MPP+) on dopaminergic neurons. Rutin is a bioflavonoid with multiple pharmacological effects, and this study investigated the neuroprotective effects of rutin in the human dopaminergic SH-SY5Y cell line using the neurotoxin MPP+. SH-SY5Y cells pretreated with rutin, were exposed to MPP+ and evaluated for cell viability, nitric oxide (NO), reactive oxygen species (ROS) and antioxidant enzymes activities. In addition, western blot techniques were used to determine the protein expression levels of γH2AX and COX-2. Rutin significantly attenuated MPP+-induced loss of cell viability, mitigated ROS and NO production and inhibited the disruption of antioxidant enzymes activity. It was also observed that rutin significantly reduced protein expression levels of γH2AX and COX-2 in SH-SY5Y cells treated with MPP+. Taken together, findings from this study tend to suggest that rutin is a promising neuroprotective compound for the treatment of PD through its effects on some of the mechanisms that characterize this neurodegenerative disease.
Evidence-Based Complementary and Alternative Medicine, 2020
In the article titled "Antiproliferative and Apoptosis Induction Potential of the Methanolic Leaf... more In the article titled "Antiproliferative and Apoptosis Induction Potential of the Methanolic Leaf Extract of Holarrhena floribunda (G. Don)", there was figure duplication . As raised on PubPeer [2], Figure KMST-6 control and KMST-6 200 μg/mL are the same. e authors could not find the original images and confirmed that the photomicrographs were directly copied into a Microsoft Word document as their record of the analysis. One or both of the photomicrographs was used in error and they should be disregarded. However, the raw data (Supplementary Materials) reflect significant differences between KMST-6 colony counts for the control and the 200 μg/ml treatment, supporting the results in the article.
The anti-cancer activities of many fermented foods and beverages are now scientifically establish... more The anti-cancer activities of many fermented foods and beverages are now scientifically established. Ogiri-egusi is a condiment prepared from fermentation of Citrullus vulgaris (melon) seeds and consumed in many countries of West Africa. Its anti-oxidative and anti-hyperlipidaemic properties have been reported. This study investigated the anti-cancer activities of the aqueous and methanolic extracts from ogiri-egusi. Cytotoxicity was investigated using the MTT and colonyformation inhibition assays while flow-cytometer based Apopercentage assay was used to quantify apoptosis in extractstreated cervical and liver cancer and normal human fibroblast cells. The inhibitory concentration responsible for killing 50% of cells after 24 h by the aqueous extract in KMST-6, HeLa, and Hep-G2 cells were estimated at 1.610, 1.020, and 1.507 mg/mL respectively. While these values reduced with increasing incubation time in cancer cells it increased in the non-cancer cell. Furthermore, the extract significantly induced apoptosis in HeLa (97 ± 0.18%) and Hep-G2 (73 ± 6.73%) cells. These findings were corroborated by cells morphologic presentations and inhibition of colony formation assay. These findings suggest that the aqueous extract from fermented Citrullus vulgaris seeds might be a nutraceutical with potential anti-cancer properties.
Glioblastoma remains the most malignant of all primary adult brain tumours with poor patient surv... more Glioblastoma remains the most malignant of all primary adult brain tumours with poor patient survival and limited treatment options. This study adopts a drug repurposing approach by investigating the anti-cancer activity of a derivative of the antipsychotic drug phenothiazine (DS00329) in malignant U251 and U87 glioblastoma cells. Results from MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and clonogenic assays showed that DS00329 inhibited short-term glioblastoma cell viability and long-term survival while sparing non-cancerous cells. Western blot analysis with an antibody to γH2AX showed that DS00329 induced DNA damage and flow cytometry and western blotting confirmed that it triggered a G1 cell cycle arrest which correlated with decreased levels in Cyclin A, Cyclin B, Cyclin D1 and cyclin dependent kinase 2 and an increase in levels of the cyclin dependent kinase inhibitor p21. DS00329 treated glioblastoma cells exhibited morphological and molecular markers typical of apoptotic cells such as membrane blebbing and cell shrinkage and an increase in levels of cleaved PARP. Flow cytometry with annexin V-FITC/propidium iodide staining confirmed that DS00329 induced apoptotic cell death in glioblastoma cells. We also show that DS00329 treatment of glioblastoma cells led to an increase in the autophagosome marker LC3-II and autophagy inhibition studies using bafilomycin A1 and wortmannin, showed that DS00329-induced-autophagy was a pro-death mechanism. Furthermore, DS00329 treatment of glioblastoma cells inhibited the phosphatidylinositol 3′-kinase/Akt cell survival pathway. Our findings suggest that DS00329 may be an effective treatment for glioblastoma and provide a rationale for further exploration and validation of the use of phenothiazines and their derivatives in the treatment of glioblastoma. Keywords Drug repurposing • Phenothiazines • Glioblastoma • Apoptosis • Autophagy Abbreviations PTZ Phenothiazine MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide γH2AX Phosphorylated H2A histone family member X CDK2 Cyclin-dependent kinase 2 PARP Poly (ADP-ribose) polymerase FITC Fluorescein isothiocyanate (FITC) LC3 Microtubule-associated protein light chain 3 FACS Fluorescence-activated cell sorting AVO Acidic vesicular organelles PI3K/Akt Phosphatidylinositol 3′ kinase/Akt MAPK Mitogen activated protein kinase ATM Ataxia-telangiectasia mutated * S.
Background: The plant Holarrhena floribunda (H. floribunda; G. Don) is indigenous to sub-Saharan ... more Background: The plant Holarrhena floribunda (H. floribunda; G. Don) is indigenous to sub-Saharan Africa and is traditionally used to treat several ailments. The present study was carried out to isolate and characterize bioactive compounds with anti-proliferative activity present in H. floribunda extracts. Methods: Compounds were isolated from H. floribunda using the bioassay-guided fractionation technique of repeated column chromatography and the step-wise application of the MTT reduction assay to assess antiproliferative bioactivity. The structures of the compounds were identified mainly using NMR. The effects of the isolated compounds on the viability, cell cycle and proliferation of human cancer cell lines (MCF-7, HeLa and HT-29) as well as the non-cancerous human fibroblast cell line (KMST-6) were investigated. Results: Bioassay-guided fractionation yielded two steroidal alkaloids: holamine (1) and funtumine (2). The MTT reduction assay shows that both compounds exhibited selective dose-dependent cytotoxicity against the cancer cell lines studied. The isolated compounds induced cell cycle arrest at the G 0 /G 1 and G 2 /M phases in the cancer cell lines with significant reduction in DNA synthesis. The results obtained show that the cancer cells (MCF-7, HeLa and HT-29) used in this study were more sensitive to the isolated compounds compared to the noncancerous fibroblast cells (KMST-6). The ability of the isolated compounds to cause cell cycle arrest and reduce DNA synthesis raises hopes for their possible development and use as potent anticancer drugs. However, more mechanistic studies need to be done for complete validation of the efficacy of the two compounds.
Many natural products and medicinal plants have been tested experimentally for validation of thei... more Many natural products and medicinal plants have been tested experimentally for validation of their reported folkloric efficacies. South Africa has abundant plant biodiversity and medicinal plants are still widely used in most parts of the country for the treatment of common neurodegenerative disorders (NDDs). However, very few studies have reported on the validation of South African medicinal plants (SAMPs) used in traditional, complementary and alternative medicine (TCAM) for the treatment of NDDs. Extensive testing provides the basis for clinical trials which progressively lead to the development of affordable indigenous and readily available products for preventing or treating NDD including Parkinson's disease (PD), one of the most common central nervous system (CNS) disorders among the elderly often characterized by the progressive loss of dopaminergic neurons (DNs) or dopamine-producing cells in the substantia nigra of the midbrain. In this study, several databases were searched to identify active compounds in SAMPs known to potentially protect neurons from progressive damage as seen in most NDDs. Our search results showed many commonly used SAMPs and their possible mechanisms of action including prevention of neuronal death by inhibition of Caspase-3 activation, MAO-B enzyme inhibition as well as restoration of glutathione content in cells. Most of the observed effects relate to the protection of DNs from degeneration, indicating the potential use of these compounds as antiparkinsonian agents. This review article therefore identifies and presents research gaps on how indigenous SAMPs could be studied more extensively for their chemical constituents and bioactivity against age-related NDDs such as PD.
The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challen... more The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challenges in the design of a single molecule that may ultimately prevent the progression of these disorders in affected patients. In this article, we report on twelve novel polycyclic amine cage derivatives, synthesized with or without a propargylamine function, designed to possess inherent multifunctional neuroprotective activity. The MTT cytotoxicity assay results showed the SH-SY5Y human neuroblastoma cells to be viable with the twelve compounds, particularly at concentrations less than 10 µM. The compounds also showed significant neuroprotective activity, ranging from 31% to 66% at 1 µM, when assayed on SH-SY5Y human neuroblastoma cells in which neurodegeneration was induced by MPP + . Calcium regulation assays conducted on the same cell line showed the compounds to be significant VGCC blockers with activity ranging from 26.6% to 51.3% at 10 µM; as well as significant NMDAr antagonists, with compound 5 showing the best activity of 88.3% at 10 µM. When assayed on human MAO isoenzymes, most of the compounds showed significant inhibitory activity, with compound 5 showing the best activity (MAO-B: IC 50 = 1.70 µM). Generally, the compounds were about 3 -52 times more selective to the MAO-B isoenzyme than the MAO-A isoenzyme. Based on the time-dependency studies conducted, the compounds can be defined as reversible MAO inhibitors. Several structure activity relationships were derived from the various assays conducted, and the compounds' possible putative binding modes within the MAO-B enzyme cavity were assessed in silico.
EUPHORBIA HIRTAISAPLANTUSEDIN TRADItional medicine for a variety of diseases, such as cough, asth... more EUPHORBIA HIRTAISAPLANTUSEDIN TRADItional medicine for a variety of diseases, such as cough, asthma, colic dysentery and genito-urinary infection. This plant, belonging to the family Euphorbiaceae, is also known as the Australian asthma herb or Queensland asthma weed, and is not toxic whentaken in typical dosages. In SouthAfrica, it is commonly used for asthma, which is one of the most common respiratory complaints. Although corticosteroids are considered the best means of defence against this debilitating illness, many people, especially in poor countries, rely on herbal remedies for its treatment. We discuss recently published results to assess the effect of the plant using the BALB/c murine asthma model. We also review the different compounds found in plant extracts, in an attempt to understand the reason for its anti-inflammatory properties. We conclude that the flavonoids quercitrin (converted to quercetin in the alimentary canal) and myricitrin, as well as the sterols 24-methy...
African journal of medicine and medical sciences, 2005
The teratogenic effect of maternal cyanide consumption on the gross morphology of the post-natal ... more The teratogenic effect of maternal cyanide consumption on the gross morphology of the post-natal phase of the developing rat cerebellum was studied. Twenty pregnant female rats weighing between 170 g and 190 g were separated into control and experimental groups. The control animals were fed a standard diet of mice cubes, while the experimental animals were fed 500 ppm potassium cyanide, mixed with the standard diet. The diets were fed to the animals and their litters in separate cages and water provided ad libitum during gestation and to the offspring after birth. After birth, the offspring (five per group) of days 1, 9, 14, 21, 28 and 50 were weighed, killed by cervical dislocation and the gross parameters studied. In the experimental animals, no significant differences were observed in the studied parameters between the control and experimental animals on day 1. A significant reduction in body weight was observed on day 14 (P < 0.05). The brain weight was significantly reduced ...
African journal of medicine and medical sciences, 2003
The present study investigates the wound healing properties of methanolic extracts of Ageratum co... more The present study investigates the wound healing properties of methanolic extracts of Ageratum conyzoides leaves compared with those of honey. Thirty Wistar rats were randomized into 3 groups of 10 animals each. They were fed with standard rat cubes and Tap water weighed and acclimatized to laboratory conditions for one week. Under anesthesia, each animal had the skin of its dorsolateral flank shaved after which an area of the skin was excised. On achieving haemostasis, the wounds were packed with gauze soaked in the appropriate dressing for each group. Measurement of wound size, and wound biopsies were taken on the 10th day post-wound creation. Together with healed wound samples, these were processed for histology. Fibroblast and blood vessel densities per unit area of wound were determined for the healed wound samples. Histologically, the day 10 Ageratum sections showed fewer inflammatory cells compared with similar honey and Control sections. Also, healed scar sections of wounds ...
tional medicine for a variety of diseases, such as cough, asthma, colic dysentery and genito-urin... more tional medicine for a variety of diseases, such as cough, asthma, colic dysentery and genito-urinary infection. This plant, belonging to the family Euphorbiaceae, is also known as the Australian asthma herb or Queensland asthma weed, and is not toxic when taken in typical dosages. In South Africa, it is commonly used for asthma, which is one of the most common respiratory complaints. Although corticosteroids are considered the best means of defence against this debilitating illness, many people, especially in poor countries, rely on herbal remedies for its treatment. We discuss recently published results to assess the effect of the plant using the BALB/c murine asthma model. We also review the different compounds found in plant extracts, in an attempt to understand the reason for its anti-inflammatory properties. We conclude that the flavonoids quercitrin (converted to quercetin in the alimentary canal) and myricitrin, as well as the sterols 24-methylene-cycloartenol and -sitosterol, exert noteworthy and dose-dependent anti-inflammatory activity. The triterpene β-amyrin also seems to exert a similar anti-inflammatory activity. Tannins and tannic acid derivatives, also present in the plant, have antiseptic effects and the two triterpenoids, taraxerone (EH-1) and 11α, 12α-oxidotaraxerol (EH-2), in E. hirta demonstrate antibacterial and antifungal properties. The effectiveness of E. hirta in treating asthma may lie predominantly in the synergistic relationships between the flavonoids, sterols and triterpenoids.
Platelets and fibrin play an important role in the coagulation process, where they are involved i... more Platelets and fibrin play an important role in the coagulation process, where they are involved in the maintenance of hemostasis. Fibrin dysfunction is associated with the development of vascular complications, while proneness to the formation of tight and rigid fibrin networks is independently associated with thrombotic disease. Here we investigate the ultrastructure of human, rabbit, and mouse platelets and fibrin networks, using the scanning electron microscope. Human and rabbit fibrin and platelets, with regards to morphology as well as size of major and minor fibers compare well with each other. However, mouse fibers are much thinner and form a flimsy branching network. Platelet aggregate morphology of all three species compare well with each other. We conclude that rabbit platelet and fibrin networks could be used successfully when studying the effect of pharmaceutical products in preclinical trials, when looking at the effects of these products on morphology and ultrastructur...
Uploads
Papers by OKOBI EKPO