Okobi Ekpo | Khalifa University (original) (raw)

Papers by Okobi Ekpo

Advances in traditional medicine, Jan 27, 2024

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.

West African journal of medicine, 2008

The effect of quinine commonly used for the treatment of Chloroquine resistant malaria and cerebr... more The effect of quinine commonly used for the treatment of Chloroquine resistant malaria and cerebral malaria on the population and transverse diameters of Purkinje cells in the cerebellar cortex was investigated. Twenty-seven adult male wistar rats weighing between 150 g and 190 g were separated into three groups, each containing nine rats. The rats in group I were injected intramuscularly with equivalent volume of physiological saline, while group II rats were injected intramuscularly with an initial 20 mg/kg body weight dose of quinine followed by a 10 mg/kg body weight dose given 8 hourly for 7 days. The group III rats received the same treatment as group II, but were subjected to a withdrawal period of one week. The cerebellum of each rat was removed and fixed in 10% formol saline for routine histological procedures. The Purkinje cell population reduced significantly (P < 0.05) from the mean value of 363 +/- 5.2 cells/mm2 in group I to a mean value of 239 +/- 9.5 cells/mm2 in ...

IBRO Neuroscience Reports

Molecules, Dec 28, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

South African Journal of Botany

Plant Science Today

South African Helichrysum species are known for diverse medicinal use and treatment of different ... more South African Helichrysum species are known for diverse medicinal use and treatment of different illnesses. Ethnopharmacological studies have revealed the potential use of Helichrysum plants in drug discovery. Although some of these species have been documented, there is still paucity of information on most species. This review seeks to provide a compilation of documented traditional uses, reproductive potential, antioxidant, anti-inflammatory, antimicrobial, protective and antidiabetic activities and other therapeutic properties of some Helichrysum species of South Africa. Information on Helichrysum cymosum, H. foetidum, H. odoratissimum, H. patulum and H. petiolare were collected from such scientific databases as Google scholar, Scifinder, PubMed, Elsevier, Scopus, Science direct in the form of journal articles, scientific reports, theses and books from the Library of the Cape Peninsula University of Technology. Our findings show that these species have historic values in traditio...

Biomedicine & Pharmacotherapy

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

Alzheimer's & Dementia, 2021

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is mainly prevalent in ... more Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is mainly prevalent in the older population. Approximately fifty million people are diagnosed with dementia, with AD accounting for 60–70% of these cases. Amyloid beta (Aβ) is considered a pathological hallmark of AD. The shorter Aβ 25 – 35 peptide fragments, formed from the amyloidogenic Aβ 1–40 peptide, plays a crucial role in the peptide’s neurotoxic activity (Pike et al., 2002). Acetylcholinesterase (AChE) as well as oxidative stress have shown to trigger Aβ formation and aggregation (Belluti et al., 2011; Cheignon et al., 2018). Previously, we synthesized multifunctional edaravone‐N‐benzyl pyridinium compounds that exhibited potent AChE inhibition and antioxidant activity as well as predicted to cross the blood‐brain barrier (BBB) using in silico models (Zondagh et al., 2020).

European Journal of Medicinal Chemistry, 2020

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,

Journal of Herbal Medicine, 2021

Neuroblastoma is a solid neuroendocrine tumour located outside the cranial cavity and contributes... more Neuroblastoma is a solid neuroendocrine tumour located outside the cranial cavity and contributes about 15% of all cancer-associated deaths in children. Treatment of neuroblastoma is quite challenging and involves the use of chemotherapy, surgery and radiotherapy. Despite treatment strategies, systemic toxicity are setbacks to patient well-being, hence the need for a new and affordable approach. Medicinal plants are of importance in the field of drug discovery for cancer as some notable anti-cancer agents have been isolated from them. In the present study, the anti-cancer activity of aqueous extract of Carpobrotus edulis (C. edulis), a ground-creeping edible medicinal plant was investigated in SK-N-BE(2) and SH-SY5Y neuroblastoma cells. The effect of C. edulis on cell viability and survival was determined using MTT (3-[4,5-dimethylthiazol-2-yl]− 2,5 diphenyltetrazolium bromide) and clonogenic assays respectively. Apoptosis was determined using a Caspase-9 assay kit and flow cytometry was used to measure intracellular reactive oxygen species (ROS) and depolarization of mitochondrial membrane potential. The results show that C. edulis inhibits cell viability (IC 50 of 0.86 mg/ml and 1.45 mg/ml for SK-N-BE (2) and SHSY5Y cells respectively) and colony formation in the neuroblastoma cells as well as induce apoptosis, which is evidenced by an increase in caspase-9 activity in the cells. C. edulis also led to a loss of mitochondrial membrane potential and increased production of ROS. Collectively, these results suggest that C. edulis induces cell death via induction of mitochondrial-mediated apoptosis and accumulation of intracellular ROS, thus providing a rationale for further investigations.

South African Journal of Botany, 2021

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.

Evidence-Based Complementary and Alternative Medicine, 2020

Food Research, 2020

Some fermented foods are reported to possess anti-cancer properties. Fermented African locust bea... more Some fermented foods are reported to possess anti-cancer properties. Fermented African locust bean seeds is a condiment prepared from fermentation of Parkia biglobosa. It has been reportedly functional for various medicinal activities but not anti-cancer. The cytotoxic and apoptosis-inducing properties of the aqueous extract of the condiment were investigated in human cancer - hepatocellular (Hep-G2) and cervical (HeLa) and noncancer cell lines. Cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) and clonogenic cell survival assays. Apoptotic cell death and DNA fragmentation were also investigated. The results revealed cytotoxicity to both cell lines in a dose-dependent manner (P < 0.05) and selective activities between cancer and non-cancer cells. The IC50 values were 1.3 and 0.5 mg/mL for Hep-G2 and HeLa cells respectively. Furthermore, the extract induced apoptotic cell death in only Hep -G2 (73.03±0.73) cells. The morpholo...

Apoptosis, 2020

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.

BMC Complementary and Alternative Medicine, 2019

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). Conclusion: 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.

UPHORBIA HIRTA IS A PLANT USED IN TRADItional medicine for a variety of diseases, such as cough, ... more UPHORBIA HIRTA IS A PLANT USED IN 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 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.

Microscopy Research and Technique, 2007

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...

Experimental and Toxicologic Pathology, 2007

The murine Balb/c asthma model has been used successfully for a number of in vivo immunological a... more The murine Balb/c asthma model has been used successfully for a number of in vivo immunological applications and for testing novel therapeutics, and it is a reliable, clinically relevant facsimile of the human disease. Here we investigate whether this model can be used to study other components of the human body, e.g. ultrastrucure. In particular, we investigate the effect of the phytomedicine Euphorbia hirta (used to treat asthma), on the ultrastructure of fibrin as well as platelets, cellular structures that both play an important role in the coagulation process. Hydrocortisone is used as positive control. Ultrastructure of the fibrin networks and platelets of control mice were compared to mice that were asthmatic, treated with two concentrations of hydrocortisone and one concentration of the plant material. Results indicate control mice possess major, thick fibers and minor thin fibers as well as tight round platelet aggregates with typical pseudopodia formation. Minor fibers of asthmatic mice have a netlike appearance covering the major fibers, while the platelets seem to form loosely connected, granular aggregates. Both concentrations of hydrocortisone make the fibrin more fragile and that platelet morphology changes form a tight platelet aggregate to a more granular aggregate not closely fused to each other. We conclude that E. hirta does not impact on the fragility of the fibrin and that it prevents the minor fibers to form the dense netlike layer over the major fibers, as is seen in untreated asthmatic mice. This ultrastructural morphology might give us better insight into asthma and the possible new treatment regimes.