<i>Morinda citrifolia</i> and Its Active Principle Scopoletin Mitigate Protein Aggregation and Neuronal Apoptosis through Augmenting the DJ-1/Nrf2/ARE Signaling Pathway

Narasimhan, Kishore Kumar S; Jayakumar, D.; Velusamy, Prema; Srinivasan, A. R.; Mohan, Thangarajeswari; Ravi, G.; Uthamaraman, Saraswathi; Sathyamoorthy, Yogesh Kanna; Rajasekaran, Namakkal S.; Kalaiselvi, Periandavan

doi:10.1155/2019/2761041

Cited by 41 publications

(27 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Scopoletin suppressed the formation of advanced glycation end products (AGEs), hyperglycemia, and insulin resistance and enhanced Nrf2, Akt, and GLUT2 in hepatocytes [121]. Very recently, Narasimhan et al reported that scopoletin protected against oxidative stress and apoptosis induced by rotenone via Nrf2 activation and investigated its neuroprotective effects for Parkinson's disease in a rat model and in vitro using SH-SY5Y cells [122].…”

Section: Urolithin Amentioning

confidence: 99%

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

164

106

View full text Add to dashboard Cite

The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.

show abstract

Section: Urolithin Amentioning

confidence: 99%

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

164

106

View full text Add to dashboard Cite

show abstract

“…Thus, it is possible that oxidation of Cys106 may act as the signal for DJ-1 to prevent mitochondrial dysfunction during ROS production in PD. In addition, DJ-1 regulates the expression of antioxidant genes by promoting nuclear translocation of Nrf2, a transcription factor that binds to genes containing an antioxidant response element (ARE) [ 41 , 47 ].…”

Section: Oxidative Stress and Park Genesmentioning

confidence: 99%

Dietary Antioxidants and Parkinson’s Disease

Park

Ellis

2020

Antioxidants

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the depletion of dopaminergic neurons in the basal ganglia, the movement center of the brain. Approximately 60,000 people are diagnosed with PD in the United States each year. Although the direct cause of PD can vary, accumulation of oxidative stress-induced neuronal damage due to increased production of reactive oxygen species (ROS) or impaired intracellular antioxidant defenses invariably occurs at the cellular levels. Pharmaceuticals such as dopaminergic prodrugs and agonists can alleviate some of the symptoms of PD. Currently, however, there is no treatment to halt the progression of PD pathology. Due to the nature of PD, a long and progressive neurodegenerative process, strategies to prevent or delay PD pathology may be well suited to lifestyle changes like dietary modification with antioxidant-rich foods to improve intracellular redox homeostasis. In this review, we discuss cellular and genetic factors that increase oxidative stress in PD. We also discuss neuroprotective roles of dietary antioxidants including vitamin C, vitamin E, carotenoids, selenium, and polyphenols along with their potential mechanisms to alleviate PD pathology.

show abstract

“…Additionally, biological studies in a rodent Parkinson’s disease model system demonstrate the neuroprotective effect of reynosin against dopamine-induced neuronal cell death [ 51 ]. Moreover, scopoletin, also present in extract, is a coumarin present in different species of plants that possess anticancer properties inducing cell cycle arrest and caspase-3 activation in the prostate cancer cell line [ 52 ], while inducing PARP cleavage and DNA fragmentation in promyeloleukemic HL-60 cells which lead to apoptosis [ 53 ]; and is able to enhance the neuronal defense system and protect the brain from rotenone-induced oxidative stress and Parkinson’s disease [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Chemical Composition, Antioxidant and Anticancer Activities of Leptocarpha rivularis DC Flower Extracts

et al. 2020

View full text Add to dashboard Cite

An evaluation of antioxidant and anticancer activity was screened in Leptocarpha rivularis DC flower extracts using four solvents (n-hexane (Hex), dichloromethane (DCM), ethyl acetate (AcOEt), and ethanol (EtOH)). Extracts were compared for total extract flavonoids and phenol contents, antioxidant activity (2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), ferric reducing antioxidant potential (FRAP), total reactive antioxidant properties (TRAP) and oxygen radical absorbance capacity (ORAC)) across a determined value of reduced/oxidized glutathione (GSH/GSSG), and cell viability (the sulforhodamine B (SRB) assay). The most active extracts were analyzed by chromatographic analysis (GC/MS) and tested for apoptotic pathways. Extracts from Hex, DCM and AcOEt reduced cell viability, caused changes in cell morphology, affected mitochondrial membrane permeability, and induced caspase activation in tumor cell lines HT-29, PC-3, and MCF-7. These effects were generally less pronounced in the HEK-293 cell line (nontumor cells), indicating clear selectivity towards tumor cell lines. We attribute likely extract activity to the presence of sesquiterpene lactones, in combination with other components like steroids and flavonoids.

show abstract

Morinda citrifolia and Its Active Principle Scopoletin Mitigate Protein Aggregation and Neuronal Apoptosis through Augmenting the DJ-1/Nrf2/ARE Signaling Pathway

Cited by 41 publications

References 42 publications

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Dietary Antioxidants and Parkinson’s Disease

Chemical Composition, Antioxidant and Anticancer Activities of Leptocarpha rivularis DC Flower Extracts

Contact Info

Product

Resources

About