Activation of Nrf2 signaling pathway by natural and synthetic chalcones: a therapeutic road map for oxidative stress

Egbujor, Melford C.; Saha, Sarmistha; Buttari, Brigitta; Saso, Luciano

doi:10.1080/17512433.2021.1901578

Cited by 40 publications

(33 citation statements)

References 163 publications

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“…There has been an increasing number of publications that detail the relationship between chalcones and Nrf2, with several studies reporting the ability of chalcones to induce Nrf2. The ability of synthetic and natural chalcones to activate the Nrf2 signaling pathway was reviewed recently [15]. Ajiboye et al [16] reported that natural chalcones lophirones B (12) and C (13) could induce Nrf2 (Figure 3).…”

Section: Activation Of Nuclear Factor-erythroid 2 P45 Subunit-related Factor 2 Pathway and Cellular Defence Genesmentioning

confidence: 99%

Chalcones: Synthetic Chemistry Follows Where Nature Leads

et al. 2021

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Chalcones belong to the flavonoid class of phenolic compounds. They form one of the largest groups of bioactive natural products. The potential anticancer, anti-inflammatory, antimicrobial, antioxidant, and antiparasitic properties of naturally occurring chalcones, and their unique chemical structural features inspired the synthesis of numerous chalcone derivatives. In fact, structural features of chalcones are easy to construct from simple aromatic compounds, and it is convenient to perform structural modifications to generate functionalized chalcone derivatives. Many of these synthetic analogs were shown to possess similar bioactivities as their natural counterparts, but often with an enhanced potency and reduced toxicity. This review article aims to demonstrate how bioinspired synthesis of chalcone derivatives can potentially introduce a new chemical space for exploitation for new drug discovery, justifying the title of this article. However, the focus remains on critical appraisal of synthesized chalcones and their derivatives for their bioactivities, linking to their interactions at the biomolecular level where appropriate, and revealing their possible mechanisms of action.

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Section: Activation Of Nuclear Factor-erythroid 2 P45 Subunit-related Factor 2 Pathway and Cellular Defence Genesmentioning

confidence: 99%

Chalcones: Synthetic Chemistry Follows Where Nature Leads

et al. 2021

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“…NRF2 is positively regulated by three MAP kinases, ERK, JNK, and p38, and the protein kinase (PKR)-like endoplasmic reticulum kinase (PERK) [ 15 ]. NRF2/ARE signaling has been considered as a promising target against oxidative stress-mediated diseases like diabetes, fibrosis, neurotoxicity, and cancer [ 16 ]. In this review, we will focus on the NRF2/ARE signaling pathway and its role in oxidative stress-mediated diseases.…”

Section: Nrf2-antioxidant Defense System Pathwaymentioning

confidence: 99%

Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2/ARE Signaling Pathway and Epigenetic Regulation

Venkidasamy²,

et al. 2021

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Oxidative stress is a pathological condition occurring due to an imbalance between the oxidants and antioxidant defense systems in the body. Nuclear factor E2-related factor 2 (NRF2), encoded by the gene NFE2L2, is the master regulator of phase II antioxidant enzymes that protect against oxidative stress and inflammation. NRF2/ARE signaling has been considered as a promising target against oxidative stress-mediated diseases like diabetes, fibrosis, neurotoxicity, and cancer. The consumption of dietary phytochemicals acts as an effective modulator of NRF2/ARE in various acute and chronic diseases. In the present review, we discussed the role of NRF2 in diabetes, Alzheimer’s disease (AD), Parkinson’s disease (PD), cancer, and atherosclerosis. Additionally, we discussed the phytochemicals like curcumin, quercetin, resveratrol, epigallocatechin gallate, apigenin, sulforaphane, and ursolic acid that have effectively modified NRF2 signaling and prevented various diseases in both in vitro and in vivo models. Based on the literature, it is clear that dietary phytochemicals can prevent diseases by (1) blocking oxidative stress-inhibiting inflammatory mediators through inhibiting Keap1 or activating Nrf2 expression and its downstream targets in the nucleus, including HO-1, SOD, and CAT; (2) regulating NRF2 signaling by various kinases like GSK3beta, PI3/AKT, and MAPK; and (3) modifying epigenetic modulation, such as methylation, at the NRF2 promoter region; however, further investigation into other upstream signaling molecules like NRF2 and the effect of phytochemicals on them still need to be investigated in the near future.

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“…In another model of inhibition of oxidative stress, GPETAFLR, a lupin-originated octapeptide, was demonstrated to increase cell viability and improve GSH synthesis, while suppressing ROS generation in retinal pigment epithelium cells [ 28 ]. This finding suggests that consumption of lupin-rich diet will provide health benefits such as delaying the onset of AMD, a condition that has been shown to be associated with free radical attack on ocular tissues, compromising the blood-retinal barrier that results in initiation and progression of ADM [ 82 , 83 , 84 ]. Taken together, these reports on the antioxidant properties of LDPs strongly position LDPs as candidates for functional food developments for diseases with oxidative stress etiology.…”

Section: Biological Activities Of Ldpsmentioning

confidence: 99%

Lupin-Derived Bioactive Peptides: Intestinal Transport, Bioavailability and Health Benefits

et al. 2021

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There is a renewed interest on the reliance of food-based bioactive compounds as sources of nutritive factors and health-beneficial chemical compounds. Among these food components, several proteins from foods have been shown to promote health and wellness as seen in proteins such as α/γ-conglutins from the seeds of Lupinus species (Lupin), a genus of leguminous plant that are widely used in traditional medicine for treating chronic diseases. Lupin-derived peptides (LDPs) are increasingly being explored and they have been shown to possess multifunctional health improving properties. This paper discusses the intestinal transport, bioavailability and biological activities of LDPs, focusing on molecular mechanisms of action as reported in in vitro, cell culture, animal and human studies. The potentials of several LDPs to demonstrate multitarget mechanism of regulation of glucose and lipid metabolism, chemo- and osteoprotective properties, and antioxidant and anti-inflammatory activities position LDPs as good candidates for nutraceutical development for the prevention and management of medical conditions whose etiology are multifactorial.

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Activation of Nrf2 signaling pathway by natural and synthetic chalcones: a therapeutic road map for oxidative stress

Cited by 40 publications

References 163 publications

Chalcones: Synthetic Chemistry Follows Where Nature Leads

Chalcones: Synthetic Chemistry Follows Where Nature Leads

Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2/ARE Signaling Pathway and Epigenetic Regulation

Lupin-Derived Bioactive Peptides: Intestinal Transport, Bioavailability and Health Benefits

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