Naturally Occurring Nrf2 Activators: Potential in Treatment of Liver Injury

Jadeja, Ravirajsinh N.; Upadhyay, Kapil; Devkar, Ranjitsinh; Khurana, Sandeep

doi:10.1155/2016/3453926

Cited by 107 publications

(75 citation statements)

References 145 publications

(141 reference statements)

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“…Honaucin A forms a covalent bond with the sulfhydryl groups on KEAP1, resulting in the activation of NRF2 [85]. Many food-based NRF2 activators have been shown to work in multiple organs such as liver [86], lung [87], kidney [88], brain [89] and gastrointestinal tract [90]. Most of these NRF2 activating compounds are phenol, polyphenol, or triterpenoid.…”

Section: Natural Compoundsmentioning

confidence: 99%

Potential Applications of NRF2 Modulators in Cancer Therapy

et al. 2020

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The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2.

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Section: Natural Compoundsmentioning

confidence: 99%

Potential Applications of NRF2 Modulators in Cancer Therapy

et al. 2020

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“…Nrf2, a member of the leucine zipper transcription factor family, is regarded as one of the pivotal regulators of cytoprotective and detoxification genes that prevent oxidative stress. 15,29 Under normal physiological conditions, Nrf2 binds to a Kelch-like ECH-associated protein (Keap1). 29 After exposure to oxidative stress, Nrf2 dissociates from Keap1 and further upregulates the transcription of multiple antioxidant response element (ARE)controlled genes, ultimately inducing the expression of a variety of antioxidant enzymes and phase II drugmetabolizing enzymes, including HO-1 and NQO1, which suppress oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

<p>Curcumin Attenuates Oxaliplatin-Induced Liver Injury and Oxidative Stress by Activating the Nrf2 Pathway</p>

Lu¹,

Wu²,

Xiang³

et al. 2020

DDDT

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Purpose: Oxaliplatin (OXA)-induced liver injury is one of the main limiting factors affecting the efficacy of OXA-based chemotherapy in patients with colorectal liver metastases. In addition, oxidative stress is an important pathophysiological mechanism of OXAinduced liver injury. Therefore, dietary antioxidants may decrease or prevent hepatic toxicity in vivo and be beneficial to OXA-based chemotherapy. Methods: An experimental OXA-induced liver injury animal model was established, and the protective effects of curcumin (CUR) against OXA-induced liver injury were investigated. ELISA was used to determine the levels of MDA, SOD, CAT, and GSH in liver tissue. The effect of CUR treatment on the expression of cytokines and the Nrf2 pathway was determined by real-time PCR and Western blotting. Results: CUR treatment alleviated OXA-induced hepatic pathological damage and splenomegaly. The protective effect of CUR was demonstrated to be correlated with inhibition of oxidative stress, inflammation, and the coagulation system. Furthermore, Western blotting revealed that CUR treatment reverses the suppression of Nrf2 nuclear translocation and increases the expression of HO-1 and NOQ1 in mice with OXA-induced liver injury. Moreover, the Nrf2 activation and hepatoprotective effect of CUR were abolished by brusatol. Conclusion: Curcumin attenuates oxaliplatin-induced liver injury and oxidative stress by activating the Nrf2 pathway, which suggests that CUR may be potentially used in the prevention and treatment of OXA-induced liver injury.

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“…One effective and economical strategy for reducing oxidative stress in the body is to consume antioxidant phytochemicals that are included in various foods, such as curcumin, quercetin and sulforaphane [4,5]. These dietary phytochemicals are considered to activate and/or induce several antioxidant proteins in host cells, mainly via the NF-E2-related factor 2 (Nrf2) pathway [6,7]. The Nrf2 pathway is an evolutionarily conserved cellular defense system against oxidative stress that induces the expression of antioxidant proteins at the transcriptional level and which indirectly eliminates oxidative stress [8,9].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Antioxidant Activity of Spice-Derived Phytochemicals Using Zebrafish

Endo

Muraki

Fuse

2020

IJMS

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Various dietary phytochemicals seem to display antioxidant activity through the NF-E2-related factor 2 (Nrf2) pathway. However, few studies have demonstrated its antioxidant effect and Nrf2 dependency at the animal level. We constructed a zebrafish-based assay system to analyze the in vivo antioxidant activity of phytochemicals and examined the activity of 10 phytochemicals derived from spices, using this system as a pilot study. Hydrogen peroxide and arsenite were used as oxidative stressors, and Nrf2 dependency was genetically analyzed using an Nrf2-mutant zebrafish line. The activities of curcumin, diallyl trisulfide and quercetin were involved in the reduction of hydrogen peroxide toxicity, while those of cinnamaldehyde, isoeugenol and 6-(methylsulfinyl)hexyl isothiocyanate were involved in the reduction of arsenite toxicity. The antioxidant activities of these phytochemicals were all Nrf2 dependent, with the exception of cinnamaldehyde, which showed strong antioxidant effects even in Nrf2-mutant zebrafish. In summary, we succeeded in constructing an assay system to evaluate the in vivo antioxidant activity of various phytochemicals using zebrafish larvae. Using this system, we found that each spice-derived phytochemical has its own specific property and mechanism of antioxidant action.

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Naturally Occurring Nrf2 Activators: Potential in Treatment of Liver Injury

Cited by 107 publications

References 145 publications

Potential Applications of NRF2 Modulators in Cancer Therapy

Potential Applications of NRF2 Modulators in Cancer Therapy

<p>Curcumin Attenuates Oxaliplatin-Induced Liver Injury and Oxidative Stress by Activating the Nrf2 Pathway</p>

Evaluation of Antioxidant Activity of Spice-Derived Phytochemicals Using Zebrafish

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