Nrf2 activator via interference of Nrf2-Keap1 interaction has antioxidant and anti-inflammatory properties in Parkinson's disease animal model

Kim, Siwon; Viswanath, Ambily Nath Indu; Park, Jong‐Hyun; Lee, Haeun; Park, A.Yeong; Choi, Ji Won; Kim, Yang Soo; Londhe, Ashwini M.; Jang, Bo Ko; Lee, Jaeick; Hwang, Hayoung; Lim, Sang Min; Pae, Ae Nim; Park, Ki Duk

doi:10.1016/j.neuropharm.2020.107989

Cited by 78 publications

(51 citation statements)

References 47 publications

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“…Furthermore, oxidative stress stimulates the activation of the redox-sensitive transcription factors, which in turn manages the expression of pro-inflammatory mediators. The Nrf2 and NF-kB pathway are closely related in the oxidative stress [ 41 ] and inflammatory [ 42 ] answers, respectively. They are transcription factors usually localized in the cytosol and regulated by Kelch-like ECH-associated protein 1 (Keap1) and IκBα inhibitor, respectively.…”

Section: Discussionmentioning

confidence: 99%

Consumption of Anacardium occidentale L. (Cashew Nuts) Inhibits Oxidative Stress through Modulation of the Nrf2/HO−1 and NF-kB Pathways

et al. 2020

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Ischemia/reperfusion injury is a severe disorder associated with a high mortality. Several antioxidant and pharmacological properties of cashew nuts (Anacardium occidentale L.) and its metabolites from different countries have recently been described. It is a medicinal plant with important therapeutic effects. This study aimed to verify the effect of an oral administration of cashew nuts in a rat model of ischemia/reperfusion (I/R). Adult male rats were subjected to intestinal I/R injury by clamping the superior mesenteric artery for 30 min and then allowing animals to 1 h of reperfusion. Rats subjected to I/R of the gut showed a significant increase in different biochemical markers. In particular, we evaluated lipid peroxidation, tissue myeloperoxidase activity, protein carbonyl content, reactive oxygen species generation and decreased antioxidant enzyme activities. Western blot analysis showed the activation of the NRF2 and NF-kB pathways. Increased immunoreactivity to nitrotyrosine, PARP, P-selectin, and ICAM-1 was observed in the ileum of rats subjected to I/R. Administration of cashew nuts (100 mg/kg) significantly reduced the mortality rate, the fall in arterial blood pressure, and oxidative stress and restored the antioxidant enzyme activities by a mechanism involving both NRF2 and NF-kB pathways. Cashew nuts treatments reduced cytokines plasma levels, nitrotyrosine, and PARP expression as well as adhesion molecules expressions. Additionally, cashew nuts decreased the intestinal barrier dysfunction and mucosal damage, the translocation of toxins and bacteria, which leads to systemic inflammation and associated organs injuries in particular of liver and kidney. Our study demonstrates that cashew nuts administration exerts antioxidant and pharmacological protective effects in superior mesenteric artery occlusion–reperfusion shock.

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Section: Discussionmentioning

confidence: 99%

Consumption of Anacardium occidentale L. (Cashew Nuts) Inhibits Oxidative Stress through Modulation of the Nrf2/HO−1 and NF-kB Pathways

et al. 2020

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“…The brains of 5 mice for each group were fixed, cut and colored with hematoxylin and eosin (H&E, Bio-Optica, Milan, Italy) and subsequently the sections were analyzed using an optical microscope connected to an imaging system (AxioVision, Zeiss, Milan, Italy), as previously described [ 30 , 35 ]. Histopathological evaluation was performed blindly using a semi-quantitative five point rating: 0 = normal, no death neuron observed; 1 = insignificant pathology, SN contained one to five death neurons; 2 = modest pathology, SN contained five to 10 death neurons; 3 = severe pathology, SN contained more than 10 death neurons; 4 = more severe pathology, SN contained only death neurons [ 48 ].…”

Section: Methodsmentioning

confidence: 99%

“…Recently, increasing evidence reports that HT and its derivates activate the phase 2 response, leading to the expression of the nuclear factor erythroid 2-related factor (Nrf2) antioxidant pathway [ 27 , 28 ]. Interestingly, Nrf2 represents a crucial mechanism of resistance to oxidative stress and inflammation in vitro and in vivo [ 29 , 30 ]. In line with these observations, Nrf2 codifies the antioxidant pathway of vitagenes, which exist to counteract various forms of stress (e.g., oxidative, environmental and proteotoxic stress).…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory and Anti-oxidant Activity of Hidrox® in Rotenone-Induced Parkinson’s Disease in Mice

et al. 2020

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Background: In developed countries, the extension of human life is increasingly accompanied by a progressive increase in neurodegenerative diseases, most of which do not yet have effective therapy but only symptomatic treatments. In recent years, plant polyphenols have aroused considerable interest in the scientific community. The mechanisms currently hypothesized for the pathogenesis of Parkinson’s disease (PD) are neuroinflammation, oxidative stress and apoptosis. Hydroxytyrosol (HT), the main component of Hidrox® (HD), has been shown to have some of the highest free radical evacuation and anti-inflammatory activities. Here we wanted to study the role of HD on the neurobiological and behavioral alterations induced by rotenone. Methods: A study was conducted in which mice received HD (10 mg/kg, i.p.) concomitantly with rotenone (5 mg/kg, o.s.) for 28 days. Results: Locomotor activity, catalepsy, histological damage and several characteristic markers of the PD, such as the dopamine transporter (DAT) content, tyrosine hydroxylase (TH) and accumulation of α-synuclein, have been evaluated. Moreover, we observed the effects of HD on oxidative stress, neuroinflammation, apoptosis and inflammasomes. Taken together, the results obtained highlight HD’s ability to reduce the loss of dopaminergic neurons and the damage associated with it by counteracting the three main mechanisms of PD pathogenesis. Conclusion: HD is subject to fewer regulations than traditional drugs to improve patients’ brain health and could represent a promising nutraceutical choice to prevent PD.

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“…Thus, the expression of human α-synuclein in the ventral midbrain of Nrf2-deficient mice leads to degeneration of nigral dopaminergic neurons and increased dystrophic dendrites, reminiscent of Lewy neurites; this neuronal loss is associated with neuroinflammation and gliosis. 123 Nrf2-deficient mice are also much more sensitive to the neurotoxic effects of MPTP than their wild-type counterparts, whereas Nrf2 activation has neuroprotective effects in Nrf2-wildtype, but not Nrf2-deficient mice in this model of PD, [124][125][126][127][128][129][130] as well as in mice expressing human α-synuclein. 94 In both models, these protective effects are associated with a decrease in oxidative damage and neuroinflammation.…”

Section: Targeting Nrf2 In Mitochondrial Dysfunction In Pdmentioning

confidence: 93%

Activation of transcription factor Nrf2 to counteract mitochondrial dysfunction in Parkinson's disease

Bento‐Pereira

Dinkova‐Kostova

2020

Medicinal Research Reviews

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Parkinson's disease (PD) is a progressive neurodegenerative disorder, for which no disease-modifying therapies are available to date. Although understanding of the precise aetiology of PD is incomplete, it is clear that age, genetic predisposition and environmental stressors increase the risk. At the cellular level, oxidative stress, chronic neuroinflammation, mitochondrial dysfunction and aberrant protein aggregation have been implicated as contributing factors. These detrimental processes are counteracted by elaborate networks of cellular defence mechanisms, one of which is orchestrated by transcription factor nuclear factor-erythroid 2 p45-related factor 2 (Nrf2; gene name NFE2L2). A wealth of preclinical evidence suggests that Nrf2 activation is beneficial in cellular and animal models of PD. In this review, we summarise the current understanding of mitochondrial dysfunction in PD, the role of

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Nrf2 activator via interference of Nrf2-Keap1 interaction has antioxidant and anti-inflammatory properties in Parkinson's disease animal model

Cited by 78 publications

References 47 publications

Consumption of Anacardium occidentale L. (Cashew Nuts) Inhibits Oxidative Stress through Modulation of the Nrf2/HO−1 and NF-kB Pathways

Consumption of Anacardium occidentale L. (Cashew Nuts) Inhibits Oxidative Stress through Modulation of the Nrf2/HO−1 and NF-kB Pathways

Anti-inflammatory and Anti-oxidant Activity of Hidrox® in Rotenone-Induced Parkinson’s Disease in Mice

Activation of transcription factor Nrf2 to counteract mitochondrial dysfunction in Parkinson's disease

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