Role of Rutin in 1-Mtthyl-4-Phenylpyridinium toxicity: Therapeutic implications for Parkinson's disease

Philosophiae Doctor - PhDParkinson’s disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. Although the etiology of PD is not completely known, it is believed to involve an association of various genetic, cellular, and environmental factors that individually or simultaneously advance neuronal degeneration. Neurotoxins such as 1-methyl-4-phenylpyridinium (MPP+) and 6-hydroxydopamine (6-OHDA) have been widely used to investigate distinct underlying mechanisms involved in the pathogenesis of PD. Presently, treatment options for PD are limited, as the available drugs are mainly focused on alleviating symptoms with limited ability to prevent disease progression. Accordingly, there is an increase in the use of natural compounds/products as potential neuroprotective agents. These neuroprotective treatments are believed to intervene in some stages in the pathogenesis of PD to suppress possible mechanisms of dopaminergic neuronal death such as apoptosis, mitochondrial dysfunction, oxidative stress, disturbances of calcium homeostasis, inflammation and autophagy. Thus, novel protective strategies for PD may be designed by targeting these mechanisms or intracellular signaling cascades that participate in PD pathogenesis

In vitro evaluation of the antiproliferative activity of Carpobrotus edulis on human neuroblastoma cells

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 (IC50 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

Aqueous leaf extract of Sutherlandia frutescens attenuates ROS-induced apoptosis and loss of mitochondrial membrane potential in MPP+-treated SH-SY5Y cells

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

Rutin as a potent antioxidant: implications for neurodegenerative disorders

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 mechanisms of action reviewed in this article include reduction of proinflammatory cytokines, improved antioxidant enzyme activities, activation of the mitogen-activated protein kinase cascade, downregulation of mRNA expression of PD-linked and proapoptotic genes, upregulation of the ion transport and antiapoptotic genes, and restoration of the activities of mitochondrial complex enzymes. Taken together, these findings suggest that rutin may be a promising neuroprotective compound for the treatment of NDs