Neurodegenerative diseases are hereditary or sporadic conditions that result in the progressive loss of the structure and function of neurons as well as neuronal death. Although a range of diseases lie under this umbrella term, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases that affect a large population around the globe. Alzheimer’s disease is characterized by the abnormal accumulation of extracellular amyloid-βplaques and intraneuronal neurofibrillary tangles in brain regions and manifests as a type of dementia in aged individuals that results in memory loss, multiple cognitive abnormalities, and intellectual disabilities that interfere with quality of life. Since the discovery of AD, a wealth of new information has emerged that delineates the causes, mechanisms of disease, and potential therapeutic agents, but an effective remedy to cure the diseases has not been identified yet. This could be because of the complexity of the disease process, as it involves various contributing factors that include environmental factors and genetic predispositions. This review summarizes the current understanding on neurodegenerative mechanisms that lead to the emergence of the pathology of AD.

Quercetin, a bioactive flavonoid with anti-inflammatory, immunosuppressive, and protective properties, is a potential agent for the treatment of rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) is the most commonly used animal model for studying the pathogenesis of RA. This study analysed the therapeutic role of quercetin in collagen-induced arthritis in C57BL/6 mice. The animals were allocated into five groups that were subjected to the following treatments: negative (untreated) control, positive control (arthritis-induced), arthritis+methotrexate, arthritis+quercetin, and arthritis+methotrexate+quercetin. Assessments of weight, oedema, joint damage, and cytokine production were used to determine the therapeutic effect of quercetin. This study demonstrated for the first time the anti-inflammatory and protective effects of quercetin in vivo in CIA. The results also showed that the concurrent administration of quercetin and methotrexate did not offer greater protection than the administration of a single agent. The use of quercetin as a monotherapeutic agent resulted in the lowest degree of joint inflammation and the highest protection. The reduced severity of the disease in animals treated with quercetin was associated with decreased levels of TNF-α, IL-1β, IL-17, and MCP-1. In conclusion, this study determined that quercetin, which was non-toxic, produced better results than methotrexate for the protection of joints from arthritic inflammation in mice. Quercetin may be an alternative treatment for RA because it modulates the main pathogenic pathways of RA.

Parkinson’s disease is a chronic, debilitating neurodegenerative movement disorder characterized by progressive degeneration of dopaminergic neurons in thesubstantia nigra pars compactaregion in human midbrain. To date, oxidative stress is the well accepted concept in the etiology and progression of Parkinson’s disease. Hence, the therapeutic agent is targeted against suppressing and alleviating the oxidative stress-induced cellular damage. Within the past decades, an explosion of research discoveries has reported on the protective mechanisms of flavonoids, which are plant-based polyphenols, in the treatment of neurodegenerative disease using bothin vitroandin vivomodels. In this paper, we have reviewed the literature on the neuroprotective mechanisms of flavonoids in protecting the dopaminergic neurons hence reducing the symptoms of this movement disorder. The mechanism reviewed includes effect of flavonoids in activation of endogenous antioxidant enzymes, suppressing the lipid peroxidation, inhibition of inflammatory mediators, flavonoids as a mitochondrial target therapy, and modulation of gene expression in neuronal cells.

Free radicals are widely known to be the major cause of human diseases such as neurodegenerative diseases, cancer, allergy and autoimmune diseases. Human cells are equipped with a powerful natural antioxidant enzyme network. However, antioxidants, particularly those originating from natural sources such as fruits and vegetables, are still considered essential. Rutin, a quercetin glycoside, has been proven to possess antioxidant potential. However, the neuroprotective effect of rutin in pheochromocytoma (PC-12) cells has not been studied extensively. Therefore, the present study was designed to establish the neuroprotective role of rutin as well as to elucidate the antioxidant mechanism of rutin in 6-hydroxydopamine (6-OHDA)-induced toxicity in PC-12 neuronal cells. PC-12 cells were pretreated with different concentrations of rutin for 4, 8 and 12 h and subsequently incubated with 6-OHDA for 24 h to induce oxidative stress. A significant cytoprotective activity was observed in rutin pretreated cells in a dose-dependent manner. Furthermore, there was marked activation of antioxidant enzymes including superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and total glutathione (GSH) in rutin pretreated cells compared to cells incubated with 6-OHDA alone. Rutin significantly reduced lipid peroxidation in 6-OHDA-induced PC-12 cells. On the basis of these observations, it was concluded that the bioflavonoid rutin inhibited 6-OHDA-induced neurotoxicity in PC-12 cells by improving antioxidant enzyme levels and inhibiting lipid peroxidation.

Reactive oxygen species (ROS) play an important role in ageing and age-related neurodegenerative changes including Parkinson’s disease (PD). PD is characterized by signs of major oxidative stress and mitochondrial damage in the pars compacta of the substantia nigra. Present study was designed to investigate whether the Centella asiatica extract (CAE) would prevent 1-methyl-4-phenyl-1,2,3,6 - tetrahydropyridine (MPTP) - induced neurotoxicity in aged Sprague-Dawley rats. Adult, male Sprague-dawley rats of 300-350 g were divided into control, C. asiatica alone, MPTP alone (20 mg/kg, for 21 days) and MPTP with C. asiatica (300 mg/kg for 21 days) groups. Effect of aqueous extract of C. asiatica on oxidative biomarker levels in corpus striatum and hippocampus homogenate was examined. MPTP-challenged rats elicited a significant increase in lipid hydroperoxides (LPO) (p < 0.01), protein-carbonyl-content (PCC) (p < 0.01) and xanthine oxidase (XO) (p < 0.01) when compared with control rats. There was a significant decrease in total antioxidants (TA) (p < 0.001), superoxide dismutase (SOD) (p < 0.001), glutathione peroxidase (GPx) (p < 0.01) and catalase (CAT) (p < 0.001) levels with MPTP treatment. Supplementation of CAE reduced LPO and PCC and significantly increased (p < 0.01) TA and antioxidant enzyme levels (p < 0.01) in corpus striatum and hippocampus. These results show that administration of C. asiatica was effective in protecting the brain against neurodegenerative disorders such as Parkinsonism.