Bioactive polyphenolics are ubiquitously present in plants and may play an important role in the prevention and management of certain human diseases. Three known flavonoids viz ...Kaemperol-3-O-rutinoside (1), quercetin-3-O-glucoside (2) and kaemperol-3-O-glucoside (3) and inseparable mixture (1:1) of quercetin-3-O-glucose/galactose (4) were isolated, and identified for the first time from Holarrhena floribunda. The antioxidant capacity using the ORAC, FRAP and TEAC assays and inhibition of lipid peroxidation were measured for isolated flavonoids. The result showed that compounds 2 and 4 showed significantly increased ORAC, TEAC, and FRAP activities with low pro-oxidant potential as well as improved lipid peroxidation inhibition levels when compared to compounds 1 and 3. The most active compounds were found to be flavonoids with a quercetin basic structure. These results imply that the isolated flavonoid glycosides are responsible for the antioxidant activity of the plant leaves and it forms the scientific basis for its traditional usage.
Even though Tulbaghia violacea has been used to treat and manage epilepsy in South Africa by traditional medicine practitioners, no evidence in any literature has shown any scientific scrutiny of the ...effectiveness of the plant species in therapy. This study was intended, therefore, to investigate the anticonvulsant effect of the leaf methanol extract of Tulbaghia violacea by studying its effect against tonic convulsion induced by either PTZ （pentylenetetrazole）, bicuculline, picrotoxin, strychnine or NMDLA （N-methyl-DL-aspartic acid） in mice. Qualitative phytochemical analysis, acute toxicity and HPLC studies were also carried out on the plant species. Leaf methanol extract of Tulbaghia violacea, phenobarbitone, diazepam or muscimol significantly antagonised PTZ, bicuculline or picrotoxin-induced convulsion. Combined treatment of sub-effective doses of T. violacea and muscimol significantly antagonised tonic convulsion induced by PTZ. T. violacea or phenobarbitone significantly antagonised strychnine-induced tonic convulsion. T. violacea or LY233053 significantly antagonised NMDLA-elicited tonic convulsion. Phenytoin or DMSO （dimethylsulfoxide） did not significantly affect the tonic convulsion produced by PTZ, bicuculline, picrotoxin, strychnine or NMDLA. The phytochemical qualitative analysis of the plant species showed the presence of alkaloids, saponins, reducing sugars, flavonoids, cardiac glycosides, triterpene steroids, quinones and tannins. The LD50 value obtained following oral administration of the plant extract was over 4000 mg/kg. The data in the present study indicate that the leaf methanol extract of T. violacea has anticonvulsant activity which is probably underpinned by GABAergic, glutaminergic and glycinergic mechanisms.
•Extracts of boophone disticha, brunsvigia bosmaniae and strumaria truncata protect SH-SY5Y cells from MPP+-induced neurotoxicity is SH-SY5Y cells.•Extracts of boophone disticha, brunsvigia bosmaniae ...and strumaria truncata prevent ROS accumulation in cells following MPP+ toxicity.•Cell morphology improved following pre-treatment with extracts of boophone disticha, brunsvigia bosmaniae and strumaria truncata.•Extracts of boophone disticha, brunsvigia bosmaniae and strumaria truncata improve ATP production in cells following MPP+ toxicity.•Extracts of boophone disticha, brunsvigia bosmaniae and strumaria truncata rescue SH-SY5Y cells from MPP+-induced apoptosis.
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. The pathological hallmarks of PD are defined by the loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain, with its characteristic clinical motor and non-motor symptoms. Current treatments for PD are mainly palliative; hence, novel neuroprotective and therapeutic approaches are needed. This study investigated the potential neuroprotective effects of three Amaryllidaceae plant extracts, Boophone disticha, Brunsvigia bosmaniae, and Strumaria truncata, in an in vitro model of PD involving the exposure of SH-SY5Y cell lines to the MPP+ neurotoxin. The protective effects of the three medicinal plants on cell viability were evaluated. The mechanism of the induced neuroprotection was investigated by measuring intracellular reactive oxygen species (ROS) levels, nitric oxide (NO) levels, adenosine triphosphate (ATP) levels, caspase 3 activity, and autophagy levels in the SH-SY5Y cells. The results showed that treatment with the extracts was protective against the toxicity induced by MPP+ in the SH-SY5Y cells. This was demonstrated by the significant increase in cell viability in the MPP+-treated cells, attenuation of intracellular ROS and NO levels, caspase 3 activity, and increased ATP activity. These findings suggest that the three extracts could be sources of novel bioactive agents with possible neuroprotective activities owing to their anti-apoptotic and antioxidant activities. Further studies are recommended to characterise the constituent compounds in these extracts to support their potential as drug discovery and development candidates.
•Aspalathus linearis and its bioactive compounds aspalathin and linearthin protect SH-SY5Y cells from MPP+-induced neurotoxicity is SH-SY5Y cells.•Aspalathus linearis, aspalathin and linearthin ...prevent ROS accumulation in cells following MPP+ toxicity.•Aspalathus linearis, aspalathin and linearthin improve ATP production in cells following MPP+ toxicity.•Aspalathus linearis, aspalathin and linearthin rescue SH-SY5Y cells from MPP+-induced apoptosis.•Cell morphology improved following pre-treatment with aspalathus linearis, aspalathin and linearthin.
Aspalathus linearis is a plant endemic to the Western Cape province of South Africa and is widely consumed as a beverage due to its numerous health benefits. It is rich in antioxidants and bioactive polyphenolic compounds including aspalathin, nothofagin and the recently reported linearthin. This study investigates the potential neuroprotective effects of the total extract of A. linearis (rooibos RB), and its bioactive compounds, aspalathin (ASP) and linearthin (LIN) in an in vitro model of Parkinson's disease, using the SH-SY5Y neuroblastoma cells and the 1-methyl-4-phenylpyridinium (MPP+) neurotoxin. The effect of increasing concentrations, 12.5, 25, and 50 µg/mL of RB as well as 2.5, 5, and 10 µg/mL of ASP or LIN on the viability of SH-SY5Y cells was investigated using the MTT assays. For neuroprotection experiments, cells were pre-treated with extracts or compounds for 2 h before exposure to 2000 µM MPP+ and thereafter cell viability was performed. The mechanism of neuroprotection was determined by the measurement of lactate dehydrogenase release (LDH), reactive oxygen species (ROS) production, adenosine triphosphate (ATP) and caspase 3/7 activities in the cells. Results show that the deleterious effects of MPP+ were attenuated by pre-treatment with either RB or the bioactive compounds ASP and LIN as evidenced by increased cell viability, reduced ROS accumulation, increased ATP levels, as well as the inhibition of apoptosis. These findings suggest that rooibos and its bioactive compounds are potential nutraceuticals that could enhance the function of neurons and in turn, slower the progression of neurodegeneration.
Purpose: To investigate the neuroprotective activity of the aqueous extract of Sutherlandia frutescens (SF) against 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in SH-SY5Y neuroblastoma cells.
...Methods: SH-SY5Y neuroblastoma cells were divided into different treatment groups: untreated cells, cells treated with MPP+ alone (2 mM), cells pretreated with SF (20 μg) prior to MPP+ (2 mM) treatment and cells treated with SF (20 μg) alone. Twenty-four hours after treatment with MPP+, cell viability was assessed by MTT assay, and changes in cell morphology, intracellular reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) as well as caspases 3/7 and 9 activities were determined.
Results: Treatment of SH-SY5Y cells with MPP+ alone significantly altered cellular morphology, increased ROS production (p = 0.005), induced a significant loss of MMP (p = 0.0011) and caused significant apoptotic cell death, via the activation of caspases 3/7 and 9 (p ≤ 0.0359). These effects were however significantly (p ≤ 0.0359) attenuated in cells pre-treated with the aqueous leaf extract of SF, indicating the possible neuroprotective activity of the SF extract.
Conclusion: The results of this study suggest that the aqueous leaf extract of SF may be neuroprotective against MPP+-induced toxicity via apoptotic cell death and inhibition of ROS production. Further mechanistic studies are required to validate the results of the present study using additional PD models, different extract preparations and active compounds derived from SF.
Keywords: Parkinson’s disease, MPP+, Sutherlandia frutescens, Reactive oxygen species, Apoptosis, Neurodegeneration
Background
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).
Method
Selected compounds were chosen to further investigate their AChE inhibitory kinetics, Aβ 25 – 35 and MPP+ attenuating ability, cytotoxicity and in vitro BBB permeability. The AChE inhibitory kinetics were determined using a modified Ellman’s method. The data was analyzed, and a double‐reciprocal Lineweaver‐Burk plot was drawn. Mode of inhibition was determined from the Lineweaver‐Burk plot. The compounds in vitro Aβ 25 – 35 and MPP+ attenuating activity and cytotoxicity at concentrations of 10 – 100 µM was assessed on the SH‐SY5Y cell line. The in vitro BBB permeability of the compounds were assessed on the b.End5 cell line.
Result
All of the compounds exhibited mixed non‐competitive – uncompetitive mode of AChE inhibition which correlate with previous molecular docking studies. Four of the five compounds exhibited no cytotoxic effects to the SH‐SY5Y cell line, with some exhibiting proliferating effects. Compound 5a, 5e and 5j caused greater cell proliferation compared to the control at 10 μM. Most of the compounds exhibited significant activity at attenuating MPP+ and Aβ 25 – 35. Compounds 5a, 5b and 5e exhibited the most promising attenuating affects over all concentrations. Compound 5e caused greater cell proliferation when compared to the control.
Conclusion
These multifunctional compounds exhibited significant neuroprotective effects against neurotoxins, especially against Aβ 25 – 35. The compounds have shown promising activity as potential anti‐Alzheimer’s agents.
•Amaryllidaceae plant family differentially induced cytotoxicity in the cells.•Five of the fourteen plant extracts showed cytotoxicity on all cell lines tested.•Amaryllis belladonna was most active ...with IC50 under 30 ug/ml for all cell lines.•The cytotoxic extracts induced morphological changes in the cells.•Three of the plant extracts had minimal cytotoxic effects on all cell lines tested.
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)-2,5-diphenyltetrazolium 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 IC50 values under 100 µg/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 µg/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.
•Clivia miniata and Nerine humilis protected SH-SY5Y cells from MPP+ toxicity.•The 2 and 4 µg/mL concentrations of extracts showed no significant cytotoxic effects.•Extracts improved ATP production ...in cells and attenuated MPP+-induced apoptosis•Cell morphology improved in SH-SY5Y cells pre-treated with both extracts.
Parkinson's disease (PD) is one of the most common neurodegenerative diseases (NDD) and mainly affects the ageing population. A significant feature of PD pathogenesis is the progressive loss of dopaminergic neurons in the substantia nigra pars compacta part of the midbrain in affected persons. This neuronal loss occurs partly due to the increased generation of reactive oxygen species (ROS) in the mitochondrial and the depletion of adenosine triphosphate (ATP) in affected neurons. In this study, the methanolic extracts of Clivia miniata (CME) and Nerine humilis (NHE) belonging to the plant family Amaryllidaceae, were investigated for their neuroprotective potential in MPP+-induced neurotoxicity in SH-SY5Y neuroblastoma cells. Cell viability was determined using the 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and cell morphology was analysed using light microscopy. Furthermore, the effects of the extracts on apoptosis and ATP production were investigated using caspase 3/7 apoptosis kit and the Promega Mitochondrial ToxGlo ATP assay kit respectively. Additionally, the antioxidant contents of extracts were evaluated using routine laboratory procedures. The results show that pre-treatment of cells with the extracts at 2 and 4 μg/mL concentrations improved cell viability as well as cell morphology by inhibiting the toxicity induced by MPP+. The extracts also improved ATP levels in cells and attenuated the apoptosis induced by MPP+. Furthermore, antioxidant assays showed that both extracts had low antioxidant activity. Findings from this study indicate that CME and NHE may be promising as neuroprotective agents for PD and warrant further investigation to determine the bioactive components of the plants that may be responsible for the observed effects.
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 IC
50
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.
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 learners and educators in studying and teaching the names, attachments, and actions of muscles of the human musculoskeletal system (upper and lower limbs). The Anat_Hub application offers a wide range of useful features for promoting active and self-regulated learning, such as 3D and AR modes, glossary, and quiz features. The application was tested with potential users, and on a variety of mobile device specifications. Very few volunteers have used AR prior to this study (13.2%). On a scale of 1 to 5, the majority of volunteers scored the application a 4 or 5. Overall, results and feedback obtained from users show that the proposed immersive anatomy system could effectively improve learner engagement and retention of anatomy concepts.
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