Role of Polyphenols in the prevention of neurodegeneration

Lots of words but absolutely nothing useful that stroke survivors can make sense of and use. 
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Nasreena Sajjad * 1 , Rohaya Ali 1 , Sumaya Hassan 1 1 ( Department of Biochemistry, University of Kashmir, India) *Corresponding author: neersanrizvi@gmail.com

ABSTRACT 

Polyphenols are common secondary metabolites in the plant kingdom; this diverse family of chemical compounds has been extensively studied in pharmacology due to its high biomedical potential and abundance in vegetables and fruits. Within the last years, a rapidly growing number of polyphenolic compounds with neuroprotective effects have been described. Many efforts have been made to explore the mechanisms behind the neuroprotective action of polyphenols. However, many pathways and mechanisms considered for mediating these effects are rather general than specific. Moreover, despite the beneficial effects of polyphenols in experimental treatment of neurodegeneration, little has been achieved in bringing them into routine clinical applications. Among the pharmacological activities attributed t o natural polyphenols are antioxidant, anti - inflammatory, antibacterial, anthelmintic, antidiabetic, antiaging and neuroprotective. Interestingly, recent clinical trials have confirmed, some of the overwhelming in vitro pharmacological studies, especially those describing orally administered polyphenols with protective effect against metabolic and neurological diseases. Future studies on this latter area are the next frontier towards expanding the current knowledge on the mode of action of plant - derived com pounds, and their metabolites, on human health. Keywords: Neurodegeneration, polyphenols, antioxidant, neuroprotection

I . INTRODUCTION 

Neurodegenerative diseases (ND) include Alzheimer’s (AD) and Parkinson’s disease (PD) and multiple sclerosis (MS) which primarily affect the neurons in the human brain and are characterized by deterioration of neurons or myelin sheath, sensory information transmission disruption , movement control, and more [1]. The greatest risk factor for ND is aging, which carries mitoc hondrial dysfunction, chronic immune - inflammatory respo nse, and oxidative stress , the major caus es of neuronal damage and death [2]. Nowadays, ND are chronic and incurable conditions whose disabling effects may continue for years or even decades representi ng an enormous disease load, regarding human suffering and economic cost. Dietary genetic , and molecular factors are important determinants in progression and intervention of neurodege nerative diseases [3]. The ND are more common and have a disproportionat e impact on countries with longer life expectancies and represent the fourth highest source of overall disease burden in the high - income countries. Plant secondary metabolites are one of the most important sources of therapeutic drugs and in fact many drug s currently in use are derived from plants. Recently, a number of natural International Journal of Management, Technology And Engineering Volume 8, Issue VIII, AUGUST/2018 ISSN NO : 2249-7455 Page No:368 medicinal plants have been tested for their therapeutic properties, showing that the raw extracts or isolated pure compounds from them have more effective properties than the whole p lant as an alternative for the treatment of ND [ 4 ]. These properties are due mainly to the presence of polyphenols alkaloids, and terpenes, among others, that are micronutrients produced by plants as secondary metabolites . There is substantial evidence (epidemiological studies, animal studies, and human clinical trials) that indicates that polyphenols reduce a wide range of pathologies [ 5 ]. II . POLYPHENOLS Natural polyphenols are most commonly found chemical compounds in consumed h erbal beverage and food . T hey constitute a large group of phytochemicals with more than 8000 identified compounds [6 ]. The primary function of these compounds is protection of plants against reactive oxygen species (ROS), produced during photosynthesis, and consumption by herbivo res . Within the previous decades, most of the studies on polyphenols have been focused on anti - oxidant properties. Along with introducing resveratrol, as a potential anti - aging agent, much focus has been placed on protective effects of various polyphenols against aging and related neurodeg< enerative disease. Increase in life span by polyphenols can be associated with increased or improved brain function. For instance, epigallocatechin gallate (EGCG) postponed the onset of neurological symptoms and prolonged life span in a mice model of amyotrophic lateral sclerosis (ALS) [ 7 ]. Long term treatment with epigallocatechin gallate increased the life span and enhanced movement abilities in a transgenic Drosophila melanogaster model of Parkinson’s disease ( PD ) [ 8 ]. Despite the prominent evidence of neuroprotective effects of polyphenols from in vitro and preclinical models, overall success in bringing these compounds into routine clinical application has been limited. Polyphenols exhibit strong potential to address the etiology of neurological disorders as they , attenuate their complex physiology by modulating several therapeutic targets at once [ 9 ]. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are e valuated by various studies[ 10 ]. Although current polyphenol researches have limited impact on clinical practice, they have strong evidence and testable hypothesis to contribute clinical advances and drug discovery towards age - related neurologic al disorders. The main mechanisms of polyphenols include their well - characterized antioxidant effects , inhibition of intracellular kinases activity, binding to cell surface receptors , and modifying cell membrane functions . A number of in vivo and in vitro studies have shown that polyphenol c atechins from green tea extract possess a protective role in neurodegeneration [ 11 ]. Pre treatment with the flavonoid epicatechin attenuated neurotoxicity induced by oxidized low - density lipopro tein in mouse - derived striatal neurons , as evidenced by apoptotic DNA fragmentation and caspase - 3 activation. Catechin conferred a similar protection to primary culture of mesencephalic neurons challenged with 6 - hydroxydopamine (6 - OHDA) [ 12 ]. Tea catechins are powerful hydrogen - donating antioxidants and free radical scavengers of reactive oxygen and nitrogen species in a number of in vitro systems. They have also been shown to inhibit lipid peroxidation induced by iron ascorbate in homogenates of brain mitochondrial > membranes and brain synaptosomes . Green tea polyphenols have been found to be more effective antioxidants than vitamins E and C on a molar basis, as indicated by their reduction potentials . In addition to their radical scavenging action, green tea catechins possess well - established metal - chelating properties. International Journal of Management, Technology And Engineering Volume 8, Issue VIII, AUGUST/2018 ISSN NO : 2249-7455 Page No:369Furthermore, it has been shown that a number of flavonoids and phenolic antioxidants activate the expression of some stress - response genes, such as phase II drug - metabolizing enzymes, glutathione S - transferase, and heme - oxygenase 1, probably via their binding to the antioxidant regulatory element (ARE) present in the promoter of their respective genes [ 13 ]. Additionally, the transcriptional activation of these stress - response genes correlated with an increase in the activity and nuclear binding of the transcription factors Nrf1 and Nrf2 to the ARE sequences contained in their promoters via activation of the MAPK pathway. Resveratrol, a polyphenol abundant in grapes and red wines, [14] inhibited Aβ 42 fibril formation and protected from Aβ neurotoxicity by inhibiting inducible nitric oxide synthase inhibition . Resveratrol, with possibly high bioavailability in lipid core nanocapsules, exhibited therapeutic action in AD [15] . Rutin has been found to control oxidative stress, malondialdehyde, and glutathione disulfide formation in SH - SY5Y neuroblastoma cells [16]. Rutin has also attenuated the inflammatory cascade by decreasing cytokines like TNF - α and IL - 1β . Ferulic acid, a phenolic acid, has also exhibited higher neuroprotection against Aβ toxicity than quercetin [ 17 ]. Recent research findings have shown that polyphenols have therapeutic relevance in both cell and animal model studies. The ability of polyphenols to improve synaptic transmission by elevating cAMP, target multiple signaling pathways, and reduce Aβ toxicity suggests their therapeutic utility for age - related disorders like AD and dementia . Epigallocatechin - 3 - gallate (EGCG) exhibited neuroprotective effects by modulating neuroinflammation an d attenuating neural damage. Quercetin, apple polyphenols , myricetin have also activated SIRT1, thus exhibiting potential in MS treatment [ 18 ]. Polyphenols with their ability to attenuate oxidative stress and inflammation present therapeutic opti on in neurodegenerative diseas e. Other pol> yphenols such as baicalein, kaempferol, caffeic acid, and EGCG have been shown to extend neuroprotection in PD studies. Similarly, polyphenolic extracts from various plants have also exhibited pharmacological role in PD studies. III