Rutin as Neuroprotective Agent: From Bench to Bedside

Abstract

Flavonoids are major dietary constituents of plant-based food that occur ubiquitously in plant kingdom where they are usually present in substantial amounts. Rutin is a flavonol-type polyphenol and consists of the flavonol quercetin and the disaccharide rutinose. Rutin has been reported to exert divers biological effects such as antitumor and antimicrobial mainly associated to its antioxidant and anti-inflammatory activities. Mental, neurological, and behavioural disorders are an important and growing cause of morbidity. Most of these disorders combine a high prevalence, early onset, progressive clinical course, and impairment of critical brain functions making them a major contributor to the global disease burden. In the present work the biological in vitro and in vivo effects and the potential therapeutic applications of rutin in neurodegenerative processes is reviewed, as well as their bioavailability and pharmacokinetics, which is essential for a better understanding of its biological effectiveness. Moreover, the present review also provides an overview of the molecular mechanisms through which rutin are proposed to exert its neuroprotective effects.

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral

“…Flavonols have shown neuroprotective effects in neurodegenerative diseases. Quercetin, rutin and some other flavonols have exhibited positive effects against pathologies such as Alzheimer’s Disease (AD), Parkinson’s disease, Huntington’s Disease, multiple sclerosis, brain ischemic injury, epilepsy neurotoxins but also for aging cognitive alterations [ 238 , 283 , 284 , 285 , 286 , 287 , 288 ]. Furthermore, flavonols have also demonstrated beneficial effects in the CNS alterations caused by HFD.…”

The role of rutin and diosmin, two citrus polyhydroxyflavones in disease prevention and treatment

“…In animal and cell-based models, proapoptotic effects of rutin in neuroblastoma, colon, lung, breast and prostate cancers were shown (Chen et al, 2013a;Guon and Chung, 2016;Saleh et al, 2019;Wu et al, 2017;Yang et al, 2000). As observed for quercetin, neuroprotective effects of rutin had been demonstrated in various models including Alzheimer's, Parkinson's and Huntington's disease which had been reviewed, recently (Budzynska et al, 2017;Enogieru et al, 2018). In different rodent and cell models for Alzheimer's disease, rutin prevented cognitive deficits by decreasing neuroinflammation and apoptotic cell death in nervous tissue (Javed et al, 2012;Park et al, 2014;Ramalingayya et al, 2017;Wang et al, 2012;Xu et al, 2014).…”

“…In contrast to cancer where proapoptotic effects are considered to be beneficial, cardiovascular protection by quercetin appears to be mediated by inhibition of apoptotic pathways and repair of endothelial cells and cardiomyoctes (Chen et al, 2013b;Dayoub et al, 2013;Jagtap et al, 2009). Protective effects of quercetin against free-radical induced endothelial cell damage and apoptosis leading to atherosclerosis had been shown to be based on inhibitory effects on NO-guanylyl cyclase signaling (Perez-Vizcaino et al, 2006 (Pari and Srinivasan, 2010) Diosmin increased antioxidative enzymes and levels of antioxidants and decreased lipid peroxidation Alloxan-induced diabetic rats (Michael et al, 2013) Diosmin decreased levels of advanced glycation end products (AGEs) Hyperglycemiainduced lens model (Patil et al, 2016) The role of rutin and diosmin Gosslau et al effects against neurological disorders such as Alzheimer's, Parkinson's and Huntington's disease as reviewed, recently (Budzynska et al, 2017;Costa et al, 2016;de Andrade Teles et al, 2018;Omar et al, 2017). The understanding of molecular mechanisms leading to these neurodegenerative diseases is still poor, but in addition to anti-inflammatory activities, a suppression of apoptotic signaling in nervous tissue, either mitochondria-or receptor-mediated were demonstrated to be one of the main underlying neuroprotective mechanisms exerted by quercetin (Ansari et al, 2009;Zhang et al, 2015).…”

“…Anti-apoptotic effects were reported to be triggered via suppression of Bax and/or activation of Sirtuin-1 signaling (Costa et al, 2016;Suganthy et al, 2016). Accordingly, quercetin induced inhibition of NFκB and STAT-1 pathways responsible for attenuation of neuroinflammation (Budzynska et al, 2017;Chen et al, 2005;Suganthy et al, 2016). In addition, quercetin stimulated NRF-2 dependent antioxidant responsive elements (NRF2-ARE) as cellular antioxidative defense system.…”

Targeting Multiple Signaling Pathways in Cancer: The Rutin Therapeutic Approach

“…Rutin also reverses endothelial dysfunction through enhancing nitric oxide production and repressing ROS responsive nucleotide-binding domain-like receptor 3 (NLRP3) [ 85 , 86 ], thereby decreasing the risk of cardiovascular disease. Rutin has been also reported to combat neurodegenerative diseases by abrogating neuroinflammation, abnormal protein accumulation, and apoptosis, as well as regulating microglia and astrocyte activation [ 87 , 88 , 89 ]. It has been documented that rutin possesses promising nephroprotective effects against nephrotoxins, such as cisplatin, vancomycin, and mercuric chloride, via mitigating inflammation, oxidative damage, apoptosis, and enhancing aquaporin 1 level [ 90 , 91 , 92 ].…”