Histological studies of the effects of oral administration of aqueous extract of Phyllanthus amarus commonly used in ethno medical practice in Africa for the management of various ailments such as kidney stones, dysentery, jaundice, diarrhoea and urogenital diseases on the kidney of adult Wistar rats were carefully studied. Rats of both sexes (n=24), average weight of 260g were randomly assigned into three groups: A, B and C of (n=8) in each group. Group A and B served as treatment groups (n=16) while group C (n=8) served as the control. The rats in the treatment groups (A & B) received 500mg/kg and 1000mg/kg body weight respectively of aqueous extract of Phyllanthus amarus orally through orogastric tube for twenty-eight days, while the control rats received equal volume of distilled water without the extract of Phyllanthus amarus added for the same period. The rats were fed with growers' mash purchased from Edo feeds and Flour Mill Ltd, Ewu, Edo state and were given water liberally. The rats were sacrificed on day twenty-nine of the experiment. The kidneys were carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H&E method. The histological findings indicated that the treated sections of the kidneys showed hypertrophy of blood vessels, mild-severe infiltrate of chronic inflammatory cells and varying degrees of tubular necrosis when compared to the control sections. The findings indicated that the administration of Phyllanthus amarus extract has some adverse effects on the kidneys of adult Wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out.

Ficus exasperata is an important medicinal plant with a wide geographical distribution in Africa particularly in Nigeria. In this study, aqueous stem bark extracts of Ficus exasperata were administered to investigate its hepatoprotective effects on Paracetamol induced liver toxicity in Wistar rats. A total of Twenty Five Wistar rats were randomly divided into five groups labeled A-E and kept in a well ventilated room. Group A served as control and were treated with distilled water. Rats in groups B-E were all treated with Paracetamol (800mg/kg body weight) but rats in group C, D and E were however pretreated with Silymarin (50 mg/kg bw), 100mg/kg bw aqueous stem bark extracts of Ficus exasperata and 200mg/kg bw aqueous stem bark extracts of Ficus exasperata respectively one hour before Paracetamol administration for fourteen days. Animals were sacrificed twenty four hours after the last treatment. Blood samples were collected into heparinized bottles for biochemical estimation of liver enzymes and the liver was harvested for routine histological examination. Paracetamol produced significant changes in biochemical parameters (increases in serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), with a reduction in Total protein) and Liver histology (damage to hepatocytes). Pretreatment with Silymarin and aqueous stem bark extracts of Ficus exasperata significantly prevented the biochemical and histological changes induced by Paracetamol in the liver. In conclusion, our histological and biochemical findings indicate that aqueous stem bark extracts of Ficus exasperata possesses hepatoprotective properties. © JASEM

Various pharmacological actions such as anti-diabetic, lipid lowering and antifungal activities have been reported for Ficus Exasperata. The aim of the present study was to investigate the effect of giving oral administration of Ficus Exasperata extract with different dosages on body weight and liver function enzymes in streptozotocin-induced diabetic rats and normal rats. Forty – Two adult Wistar rats of both sexes weighing between 200 – 235g were used for this study. The rats were bred in the animal holding of the Department of Anatomy, University of Benin, Benin City. The animals were randomly assigned into seven groups of Six rats each. Group 1 was the Normal Control Group. Group 2 served as Diabetic Control Group without extract treatment. Group 3 was the experimentally induced diabetic rats treated with a standard anti-diabetic drug 5mg/kg of Glibenclamide. Group 4 was the experimentally induced diabetic rats treated with aqueous extracts of 100 mg/kg of Ficus Exasperata. Grou...

The hepatoprotective activity of aqueous leaf extracts of Phyllanthus amarus (a small herb well known for its medicinal properties and widely used worldwide) was studied on acetaminophen induced hepatotoxicity in wistar rats. Animals in Group 1 served as control animals. Acetaminophen at 800 mg/kg body weight (bw) was administered daily to induce liver toxicity in Group 2 animals. Animals in group 3 were pre-treated with Silymarin (reference drug) at 50 mg/kg bw before acetaminophen (800mg/kg) administration. Animals in Groups 4 and 5 were pre-treated with aqueous leaf extracts of Phyllanthus amarus (100mg/kg and 200mg/kg) before acetaminophen (800mg/kg) administration. The experiment lasted for 14 days. Histological findings suggests that pre-treatment with silymarin and aqueous leaf extracts of phyllanthus amarus significantly protected the liver against acetaminophen induced damage when compared to those administered with acetaminophen only. Biochemical analysis also showed signi...

Also, the exposure of humans to certain toxic environmental chemicals such as the carcinogen, carbon tetrachloride (CCl4), has been reported to play a role in the induction of NAFLD. 9, 10 CCl4 was well known for its use as a dry-cleaning agent, vermicide (kills worms) and refrigerant until its toxicity was established and its use was thereafter limited. 11 CCl4 is quite stable and is a well-known environmental pollutant which may pollute the air and also contaminate groundwater supplies. 9 CCl4 is a widely established hepatotoxin and is routinely used in animal models for inducing liver damage. 12-14 CCl4 induced liver damage is characterized by increased generation of free radicals, build-up of inflammatory cytokines, toxic lipid and protein peroxidation production leading to steatosis, fibrosis and necrosis of hepatocytes. 15-18 These adverse effects of CCl4 have been attributed to cleavage of CCl4 to its toxic reactive metabolites, trichloromethyl free radicals by cytochrome P450 enzyme. 19, 20 Plant extracts and plant-derived natural products have been previously reported to mitigate increased ROS activities and liver toxicity induced by CCl4. 21-24 A notable medicinal plant is M. cecropioides, also known as the umbrella tree and mostly found in the tropical forests of West Africa stretching from Guinea to Congo. Traditionally, the plant is used to induce labour, reduce elevated blood pressure, reduce high blood sugar, as well as treat cough, chest infection, malaria and jaundice. 25-28 Other validated pharmacological activities for the stem bark aqueous and ethanol extracts include its hypotensive and hypoglycemic effects in experimental animal models. 29-32 The leave extracts have also been reported to possess vasodilating, hypotensive, anti-inflammatory and anti-nociceptive activities in animal models. 33-36 Considering the biological activities reported for M. cecropioides, this study therefore investigates the potential hepatoprotective activity of M. cecropioides in CCl4-induced liver injury as a model of NAFLD, with silymarin as a reference standard (pharmacological control).

An in vitro medium-throughput screen using M. tuberculosis H37Rv was employed to screen an in-house library of structurally diverse compounds for antimycobacterial activity.  From this initial screen, eleven 7-substituted coumarin derivatives with confirmed monoamine oxidase-B and cholinesterase inhibitory activities, demonstrated growth inhibition of more than 50% at a 50 µM concentration.  This prompted further exploration of all the 7-substituted coumarins in our library, nineteen in total, as potential antimycobacterial agents. Four derivatives showed promising antimycobacterial activity with MIC99 values of 8.31 – 29.70 µM and 44.15 – 57.17 µM on M. tuberculosis H37Rv in independent assays using Gaste-Fe and 7H9 + OADC media, respectively.   These compounds were found to bind to albumin which may explain the variations in MIC between the two assays.  Preliminary antimycobacterial evaluation of moxifloxacin resistant M. tube...

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.

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.

Also, the exposure of humans to certain toxic environmental chemicals such as the carcinogen, carbon tetrachloride (CCl4), has been reported to play a role in the induction of NAFLD. 9, 10 CCl4 was well known for its use as a dry-cleaning agent, vermicide (kills worms) and refrigerant until its toxicity was established and its use was thereafter limited. 11 CCl4 is quite stable and is a well-known environmental pollutant which may pollute the air and also contaminate groundwater supplies. 9 CCl4 is a widely established hepatotoxin and is routinely used in animal models for inducing liver damage. 12-14 CCl4 induced liver damage is characterized by increased generation of free radicals, build-up of inflammatory cytokines, toxic lipid and protein peroxidation production leading to steatosis, fibrosis and necrosis of hepatocytes. 15-18 These adverse effects of CCl4 have been attributed to cleavage of CCl4 to its toxic reactive metabolites, trichloromethyl free radicals by cytochrome P450 enzyme. 19, 20 Plant extracts and plant-derived natural products have been previously reported to mitigate increased ROS activities and liver toxicity induced by CCl4. 21-24 A notable medicinal plant is M. cecropioides, also known as the umbrella tree and mostly found in the tropical forests of West Africa stretching from Guinea to Congo. Traditionally, the plant is used to induce labour, reduce elevated blood pressure, reduce high blood sugar, as well as treat cough, chest infection, malaria and jaundice. 25-28 Other validated pharmacological activities for the stem bark aqueous and ethanol extracts include its hypotensive and hypoglycemic effects in experimental animal models. 29-32 The leave extracts have also been reported to possess vasodilating, hypotensive, anti-inflammatory and anti-nociceptive activities in animal models. 33-36 Considering the biological activities reported for M. cecropioides, this study therefore investigates the potential hepatoprotective activity of M. cecropioides in CCl4-induced liver injury as a model of NAFLD, with silymarin as a reference standard (pharmacological control).

A wide range of neurodegenerative diseases (NDs), including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and prion diseases, share common mechanisms such as neuronal loss, apoptosis, mitochondrial dysfunction, oxidative stress, and inflammation. Intervention strategies using plant-derived bioactive compounds have been offered as a form of treatment for these debilitating conditions, as there are currently no remedies to prevent, reverse, or halt the progression of neuronal loss. Rutin, a glycoside of the flavonoid quercetin, is found in many plants and fruits, especially buckwheat, apricots, cherries, grapes, grapefruit, plums, and oranges. Pharmacological studies have reported the beneficial effects of rutin in many disease conditions, and its therapeutic potential in several models of NDs has created considerable excitement. Here, we have summarized the current knowledge on the neuroprotective mechanisms of rutin in various experimental models of NDs. The mechan...

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by selective loss of dopamine neurons in the substantia nigra pars compacta of the midbrain. Reports from postmortem studies in the human PD brain, and experimental PD models reveal that endoplasmic reticulum (ER) stress is implicated in the pathogenesis of PD. In times of stress, the unfolded or misfolded proteins overload the folding capacity of the ER to induce a condition generally known as ER stress. During ER stress, cells activate the unfolded protein response (UPR) to handle increasing amounts of abnormal proteins, and recent evidence has demonstrated the activation of the ER chaperone GRP78/BiP (78 kDa glucose-regulated protein/binding immunoglobulin protein), which is important for proper folding of newly synthesized and partly folded proteins to maintain protein homeostasis. Although the activation of this protein is essential for the initiation of the UPR in PD, there are inconsistent reports o...

Glioblastoma (GBM) is the most common and aggressive intracranial tumour with limited therapeutic options due to their high tumour vasculature and invasiveness. Treatment of GBM includes surgery, followed by chemotherapy and radiotherapy. Despite these treatment options, tumour relapse is still a major issue hence the need for cheap and effective treatment strategies. South Africa is endowed with numerous medicinal plants including Sutherlandia frutescens (S. frutescens) and Carpobrotus edulis (C.edulis), which has been previously reported for their antioxidant and neuroprotective activities. Accordingly, this study was designed to investigate the cytotoxicity of both medicinal plants (S. frutescens and C. edulis) in malignant human GBM cells U251 and U87. The cytotoxic activity was measured using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay while the effect of extracts on colony formation and survival was determined using clonogenic assay. Results show that both S. frutescens and C .edulis induced cytotoxicity in both GBM cells and inhibit colony formation in U251 cells. These findings show that extracts from these plants may be useful in the treatment of GBM and thus requires further investigations into their mechanisms of action as well as isolation of bioactive components responsible for these activities.

Parkinsonism is a degenerative neurological syndrome usually resulting from deficiency of the neurotransmitter dopamine amongst other changes in the basal ganglia. Research however, still lacks a holistic and side-effect-free therapy for the disease. Nigella sativa oil is from a multi-potent plant seed known for its historical and scientifically established therapeutic potentials. This thus investigated the anti-psychotic potentials of Nigella sativa oil (NSO) on the histology and neurochemistry in MPTP-induced mice models of Parkinsonism.Thirty-two (32) male albino mice weighing between 18-25 g were divided equally into control (administered with normal feed for 4 days), MP (administered with 18 mg/kg MPTP i.p for 4 days), NS (administered with 1 ml/kgbw NSO p.o. for 4 days), NSMP (administered with 1 ml/kgbw NSO p.o. followed by 18 mg/kg MPTP i.p for 4 days. Object Location test (OLT) was conducted, and the animals were weighed and euthanised 24 hours after last administration. The brain was excised and the striatum assayed neurochemically for dopamine and illustrated histologically using the H&E and Golgi stains. The striatal dopamine level in the MP Group was the lowest when compared with other groups, while NSMP had higher dopamine level than the parkinsonic MP mice. Histologically, the MP mice further revealed striatal loss of neurons as known with Parkinsonism, but Nigella sativa was able to prevent this significantly in the NSMP mice (p < 0.05). Nigella sativa was also able to keep the recognition memory in the Parkinsonic mice (NSMP) at par with those in the NS group. Nigella sativa Oil, through this research, showed protective properties in striatal histology and neurochemistry of parkinsonic mice. The research was conducted in conformance with the ACUREC guidelines of the

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). Th...

Accumulating evidence suggest that apoptosis, autophagy and dysregulation of signaling pathways are common mechanisms involved in Parkinson's disease (PD) pathogenesis, and thus development of therapeutic agents targeting these mechanisms may be useful for the treatment of this disease. Although rutin (a bioflavonoid) is reported to have pharmacological benefits such as antioxidant, anti-inflammatory and antitumor activities, there are very few reports on the activity of this compound in 1-methyl-4phenylpyridinium (MPP +)-induced PD models. Accordingly, we investigated the effects of rutin on apoptosis, autophagy and cell signaling markers (AKT/AMPK) in SH-SY5Y cells exposed to MPP +. Results show reduced changes in nuclear morphology and mitigation of caspase 3/7 and 9 activities in rutin pre-treated cells exposed to MPP +. Likewise, rutin regulated cell signaling pathways (AKT/AMPK) and significantly decreased protein expression levels of cleaved PARP, cytochrome c, LC3-II and p62. Also, rutin significantly increased protein expression levels of full-length caspase 3 in SH-SY5Y cells treated with MPP +. Transmission electron microscope (TEM) images demonstrated a reduction in autophagosomes in rutin-pretreated SH-SY5Y cells exposed to MPP +. These results provide experimental support for rutin's neuroprotective activity against MPP +-induced toxicity in SH-SY5Y cells, which is as a promising therapeutic agent for clinical trials in humans.

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.

Background: Sutherlandia frutescens (S. frutescens) is a shrub with attractive flowers used traditionally by in South African to treat a variety of health conditions. Its anti-cancer activity has been reported in a number of cancers, and accordingly, this study was designed to investigate the cytotoxic activity and apoptosis-inducing effects of S. frutescens in neuroblastoma cells, a type of childhood cancer and a leading cause of death in children. Method: In this study, the effect of S. frutescens on cell viability and survival of SKNBE(2) and SHSY5Y neuroblastoma cells was determined using the MMT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide) cell viability assay and clonogenic assay respectively. Furthermore, flow cytometry was used to investigate the accumulation of intracellular reactive oxygen species (ROS) as well as loss of mitochondrial membrane potential (MMP). Caspase-9 activation was also used to detect apoptosis in these cells. Results: The results fro...

Background: Turmeric (Curcuma longa), belonging to the Zingiberaceae family, is a widely used spice in cuisines of African, Asian and other countries globally. Despite the enormous pharmacological benefits of turmeric, there is very little experimental evidence to demonstrate its protective activity against cadmium-induced neurotoxicity. Accordingly, this study is aimed at investigating such activity in Wistar rats and its possible mechanisms of action. Methods: Y-maze and Novel object recognition tests were utilized to evaluate memory impairments while antioxidants activity and lipid peroxidation were evaluated to outline the antioxidant mechanism of action following pre-treatment of rats with ethanolic turmeric root extract (200 mg/kg body weight) 1 hour before cadmium administration for 21 consecutive days. In addition, the histology of the cerebrum and hippocampus was investigated to determine possible anatomical alterations across experimental groups. Results: The ethanolic ext...

Mercury (Hg) exposure is known to damage vital components of the central nervous system primarily through oxidative stress. Although Phyllanthus amarus (PA) is reported to be rich in antioxidants, there is a dearth of relevant research evidence to show its protective activity against Mercuric chloride (HgCl2)-induced neurotoxicity. Accordingly, this study was designed to investigate the possible protective activity of aqueous Phyllanthus amarus leaf extract (APALE) in HgCl2-exposed rats using standard neurobehavioral assessments. Thirty adult Wistar rats were randomized into six groups of five rats each viz: A: Control, distilled water; B: HgCl2 (4 mg/kg body wt.); C: APALE (200 mg/kg body wt.) + HgCl2 (4 mg/kg); D: APALE (400 mg/kg body wt.) + HgCl2 (4 mg/kg); E: APALE (200 mg/kg body wt.); F: APALE (400 mg/kg body wt.). All administrations were through an orogastric tube for 14 days. Thereafter, neurobehavioral tests (open field, novel object and Y-maze) were done and experimental...