Preliminary investigation of the neuroprotective potentials of Crossyne guttata in MPP+-induced toxicity in SH-SY5Y

Parkinson's disease (PD) is a movement disorder caused by the gradual and sustained loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). There is presently no permanent treatment for PD, thus the need for more investigations into complementary and alternative medicine capable of inhibiting neuronal damage. This study investigates the potential neuroprotective activity of Crossyne guttata, a plant commonly found in the western and southern Cape of South Africa in 1-methyl-4-phenylpyridinium (MPP+)-induced, in vitro model of PD, using the SH-SY5Y neuroblastoma cells.Methodology: The optimal concentration of Crossyne guttata aqueous extract (CGE) that showed no toxicity on cells and the concentration of MPP+ that reduced cell viability to about 50% was determined using the 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Following this SH-SY5Y cells were pretreated with 10 μg/ml of CGE for 2 hours before the addition of 2000 μM of MPP+ and cell survival was determined. Furthermore, morphological changes associated with treatments were observed under the light microscope.Results: Results show that CGE did not reduce cell viability in the cells at all concentrations tested, while MPP+ showed a dose-dependent reduction in cell viability. Also, pretreatment of cells with CGE extract improved cell survival as well as cell morphology by inhibiting toxicity induced by MPP+.Conclusion: Findings from this study suggest that CGE may be a potential neuroprotective agent in PD and thus make a case for further investigation into the mechanism(s) of action as well as bioactive components of the plant eliciting such effects.Keywords: Crossyne guttata, Medicinal plants, 1-methyl-4-phenylpyridinium (MPP+), Cell viabilit

Regulation of AKT/AMPK signaling, autophagy and mitigation of apoptosis in Rutin-pretreated SH-SY5Y cells exposed to MPP+

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-4-phenylpyridinium (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

Antioxidant and apoptosis-inhibition potential of Carpobrotus edulis in a model of parkinson’s disease

Background: Parkinson’s disease (PD) is a neurological disorder resulting from the progressive loss of dopaminergic neurons. There is currently no known cure for PD, thus the search for complementary and alternative medicines capable of halting the degeneration of dopaminergic neurons is plausible. Carpobrotus edulis (CE) is an indigenous plant used in South African traditional medicine used for the treatment of a number of disease conditions including tuberculosis, diabetes mellitus and constipation. It has been suggested that CE contains bioactive compounds which are responsible for its acclaimed medicinal potential. No studies have been reported on the potential benefit of CE to the nervous system. This study was therefore done to evaluate the protective effects of CE against 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in the dopaminergic SH-SY5Y cell line, as well as its underlying mechanism. Methods: In this study, SH-SY5Y cells were treated with varying concentrations of CE and MPP+ respectively to determine the optimal concentrations of MPP+ and CE for further experiments. Thereafter, SH-SY5Y cells were pre-treated with 30 μM of CE before exposure to 2 mM of MPP+ to induce cellular damage. Cell viability was evaluated using the MTT assay, intracellular reactive oxygen species (ROS) production was determined using flow cytometry and the Hoechst nuclear staining was used to visualize apoptosis. Caspases 3/7 and 9 activity was assessed using commercially available kits. Results: MPP+ treatment induced marked cell viability, increased the number of condensed nuclei and apoptotic cells, increased ROS production, initiated caspase 9 and activated caspase 3/7 in SH-SY5Y cells. The observed effects of MPP+-induced toxicity were attenuated by the pre-treatment of SH-SY5Y cells with 30 μM of CE. Conclusion: The protective effects of CE against MPP+-induced toxicity in SH-SY5Y cells may be attributed to its antioxidant and anti-apoptotic properties

Stem Bark Extracts of Ficus exasperata protects the Liver against Paracetamol induced toxicity in Wistar Rats

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

Extracts of Hunteria umbellata reverses the effect of streptozotocin‑induced pancreatic islet‑cell destruction

The use of extracts of plant parts in the treatment and/or management of diabetes mellitus has formed the basis of health care in most African countries. The aim of this study was to investigate the possible effect of oral administration of extracts Hunteria umbellata (HU) leaves and seeds on streptozotocin- induced pancreatic β-cell damage. Twenty four (24) adult wistar rats were selected into two control group (negative control group A and positive control group B) and two treatment groups (C & D) each containing six animals each (n= 6 per group). Rats in the positive control group (B) were giving intraperitoneal injection of with 50 mg/kg body weight of Streptozotocin (STZ) prepared with 0.05M Citrate buffer solution while the negative control group A rats were injected with a corresponding volume of Citrate buffer without STZ. Rats in the treatment groups were treated with 250 mg/kg body weight aqueous extract of seeds of Hunteria umbellata (group C) and 250 mg/kg body weight aqueous extract of leaves of Hunteria umbellata (group D) respectively. Blood samples were taken by repeated needle puncture of their tail tip vein every 72 hours at the end of a 12 hrs fasting. Fasting blood glucose was determined using a fine test glucometer and compatible glucose test strips. Rats were sacrificed by cervical dislocation on the 15th day and the pancreas was accessed and dissected out through a midline incision of the anterior abdominal wall of the rats. The pancreas was fixed in 10% buffered formal saline for routine histological examination. 5ml blood samples were collected in heparin coated tubes for serum anti-oxidant estimation. Results obtained showed that HU seeds and leaves extracts significantly (P < 0.05) increased Superoxide dismutase (SOD) and Catalase (CAT) activities and decrease in the activity of Thiobarbituric acid reactive species (TBARS) when compared streptozotocin injected rats. Histological sections showed marked distortion, vacoulation of the central part of the Islet. Treatment with Hunteria umbellata seed and leaf extracts reversed the cytoarchitectural distortion of pancreatic Islet cells caused by Streptozotocin. This suggests that extracts of HU seeds and leaves posses antidiabetic potential.Keywords: Hunteria umbellata, streptozotocin, pancreatic Islet, cytoarchitectural distortio