Different roles of Nrf2 and NFKB in the antioxidant imbalance produced by esculetin or quercetin on NB4 leukemia cells

Rubio, Virginia; García-Pérez, Ana Isabel; Herráez, Ángel; Diez, José C.

doi:10.1016/j.cbi.2018.08.015

Cited by 34 publications

(30 citation statements)

References 53 publications

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“…Generally, the activation of the transcription factor Nrf-2 is induced by cellular oxidative stress and acts as a marker of pro-oxidant stressors and electrophiles [76,80]. Many research groups have shown strong interaction between Nrf-2 and NF-κB [81,82]. Thimmulappa et al (2006) [83] revealed that Nrf-2-deficient mice showed enhanced NF-κB activation with treatment with lipopolysaccharides.…”

Section: Discussionmentioning

confidence: 99%

Myricetin Abrogates Cisplatin-Induced Oxidative Stress, Inflammatory Response, and Goblet Cell Disintegration in Colon of Wistar Rats

Rehman

Rather

2019

Plants

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Cisplatin [cis-diamminedichloroplatinum II] is an extensively prescribed drug in cancer chemotherapy; it is also useful for the treatment of diverse types of malignancies. Conversely, cisplatin is associated with a range of side effects such as nephrotoxicity, hepatotoxicity, gastrointestinal toxicity, and so on. Myricetin (3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)-4chromenone) is a very common natural flavonoid found in fruits, tea, and plants. It has been found to have high-value pharmacological properties and strong health benefits. To examine the role of myricetin in colon toxicity induced by cisplatin, we conducted a concurrent prophylactic study in experimental animals that were treated orally with myricetin for 14 days at two doses—25 and 50 mg/kg of body weight. On the 14th day, a single intraperitoneal injection of cisplatin (7.5 mg/kg body weight) was administered in all groups except control. The effects of myricetin in cisplatin-induced toxicity in the colon were assessed in terms of antioxidant status, phase-II detoxification enzymes, the level of inflammatory markers, and goblet cell disintegration. Myricetin was found to restore the level of all the antioxidant enzymes analyzed in the study. In addition, the compound ameliorated cisplatin-induced lipid peroxidation, increase in xanthine oxidase activity, and phase-II detoxifying enzyme activity. Myricetin also attenuated deteriorative effects induced by cisplatin by regulating the level of molecular markers of inflammation (NF-κB, Nrf-2, IL-6, and TNF-α), restoring Nrf-2 levels, and controlling goblet cell disintegration. The current study reinforces the conclusion that myricetin exerts protection in colon toxicity via up-regulation of inflammatory markers, improving anti-oxidant status, and protecting tissue damage.

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Section: Discussionmentioning

confidence: 99%

Myricetin Abrogates Cisplatin-Induced Oxidative Stress, Inflammatory Response, and Goblet Cell Disintegration in Colon of Wistar Rats

Rehman

Rather

2019

Plants

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“…Several studies have supported the involvement of Nrf2 signaling in the pharmacological activities of esculetin. For instance, the study of Rubio et al illustrated the different roles of NF-κB and Nrf2 in the antioxidant imbalance produced by esculetin on leukemia cells and concluded that esculetin resulted in a significant increase in the nuclear translocation of Nrf2 [164]. A recent study conducted by Xu et al showed that esculetin attenuated neurological defects and alleviated cognitive impairments in transient bilateral common carotid artery occlusion in mice via Nrf2 activation and markedly ameliorated mitochondrial fragmentation and stress [165].…”

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

147

101

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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.

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“…The interest in the mechanisms that promote oxidative stress, a common condition in several critical pathologies, including immunological diseases, has been accompanied by increasing research in Nrf2 signaling. Several authors have attributed an anti-inflammatory profile to Nrf2, indicating its role in the transcriptional, and post-translational inhibition of some components of the inflammatory system, such as NFκB, proinflammatory cytokines, autophagy factors, and Tolllike receptors (Kobayashi et al, 2016;Kapuy et al, 2018;Rubio et al, 2018). The balance between the antioxidant and pro-inflammatory profile promoted by Nrf2 makes it the center of attention when the immune system is modulating infectious pathologies.…”

Section: Nrf2 and The Immune System Modulationmentioning

confidence: 99%

The Potential Role of Nrf2 Signaling in Leishmania Infection Outcomes

Vivarini

Lopes

2020

Front. Cell. Infect. Microbiol.

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Nrf2 [nuclear factor erythroid 2-related factor 2 (Nrf2)] regulates the expression of a plethora of genes involved in the response to oxidative stress due to inflammation, aging, and tissue damage, among other pathological conditions. Deregulation of this cytoprotective system may also interfere with innate and adaptive immune responses. Oxidative burst, one of the main microbicidal mechanisms, could be impaired during initial phagocytosis of parasites, which could lead to the successful establishment of infection and promote susceptibility to diseases. A wide diversity of infections, mainly those caused by intracellular pathogens such as viruses, bacteria, and protozoan parasites, modulate the activation of Nrf2 by interfering with post-translational modifications, interactions between different protein complexes and the immune response. Nrf2 may be induced by pathogens via distinct pathways such as those involving the engagement of Toll-like receptors, the activation of PI3K/Akt, and endoplasmic reticulum stress. Recent studies have revealed the importance of Nrf2 on leishmaniasis. This mini-review discusses relevant findings that reveal the connection between Leishmania-induced modifications of the host pathways and their relevance to the modulation of the Nrf2-dependent antioxidative response to the infection.

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Different roles of Nrf2 and NFKB in the antioxidant imbalance produced by esculetin or quercetin on NB4 leukemia cells

Cited by 34 publications

References 53 publications

Myricetin Abrogates Cisplatin-Induced Oxidative Stress, Inflammatory Response, and Goblet Cell Disintegration in Colon of Wistar Rats

Myricetin Abrogates Cisplatin-Induced Oxidative Stress, Inflammatory Response, and Goblet Cell Disintegration in Colon of Wistar Rats

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

The Potential Role of Nrf2 Signaling in Leishmania Infection Outcomes

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