Rutin as a Potent Antioxidant: Implications for Neurodegenerative Disorders

Oxidative Medicine and Cellular Longevity, Jun 2018

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.

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Rutin as a Potent Antioxidant: Implications for Neurodegenerative Disorders

Rutin as a Potent Antioxidant: Implications for Neurodegenerative Disorders Adaze Bijou Enogieru,1 William Haylett,2 Donavon Charles Hiss,1 Soraya Bardien,2 and Okobi Eko Ekpo1 1Department of Medical Biosciences, University of the Western Cape, Robert Sobukwe Road, Private Bag X17, Bellville 7535, South Africa 2Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa Correspondence should be addressed to Okobi Eko Ekpo; az.ca.cwu@opkeo Received 9 March 2018; Accepted 29 April 2018; Published 27 June 2018 Academic Editor: Renata Szymanska Copyright © 2018 Adaze Bijou Enogieru et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract 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. 1. Introduction Neurodegenerative diseases (NDs) are regarded as an age-related group of chronic and untreatable conditions which constitutes a major threat to human health [1]. They are becoming increasingly prevalent, due to a significant increase in the size of elderly populations worldwide [2]. NDs represent the fourth highest source of disease burden in high-income countries, in terms of economic cost for society [3]. NDs are characterized by the gradual and progressive loss of neurons and diverse clinical features such as memory and cognitive impairments and others affecting a person’s ability to move, speak, and breathe [4–6]. Some overlapping pathways recognized in the pathogenicity of NDs include free radical formation and oxidative stress, protein misfolding and aggregation, metal dyshomeostasis, phosphorylation impairment, and mitochondrial dysfunction [7] (Figure 1). Figure 1: Various processes shown to be dysregulated in neurodegenerative disorders. Oxidative stress has been shown by many studies to be a crucial player in the development and progression of NDs [8]. Oxidative stress is defined as the disturbance in balance between prooxidant and antioxidant levels and results from an imbalance between the production of reactive oxygen species (ROS) and the biological system’s ability to detoxify the reactive intermediates [8]. ROS play important roles in mediating cellular activities [9, 10]; however, due to their reactivity, high amounts of ROS can cause cell death or oxidative stress [11]. While it is still unclear whether ROS is the triggering factor for NDs, they are likely to aggravate disease progression through oxidative damage and effects on mitochondria. In view of the important roles of oxidative stress in NDs, the manipulation of ROS levels may be an encouraging treatment option to delay neurodegeneration and attenuate associated symptoms. Presently, there is no potent treatment for NDs and the available drugs are mainly focused on symptoms though with many adverse effects and limited ability to prevent disease progression [12]. Accordingly, medicinal plants such as Hypericum perforatum possessing antioxidant properties have been studied for their potential to attenuate neurodegenerative symptoms [13–16]. For instance, previous reports show that extracts of H. perforatum significantly attenuated oxidative stress by reducing lipid peroxidation [17], reducing oxidation of the mitochondrial lipid membrane [18], preserving the activities of antioxidant enzymes [19], and consequently preventing neurotoxicity in experiment (...truncated)


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Adaze Bijou Enogieru, William Haylett, Donavon Charles Hiss, Soraya Bardien, Okobi Eko Ekpo. Rutin as a Potent Antioxidant: Implications for Neurodegenerative Disorders, Oxidative Medicine and Cellular Longevity, 2018, 2018, DOI: 10.1155/2018/6241017