Inhibitors of transcription factor nuclear factor-kappa beta (NF-κβ)-DNA binding

Sharma, Rakesh Kumar; Otsuka, Masami; Gaba, Garima; Mehta, Swati

doi:10.1039/c2ra21852f

Cited by 10 publications

(3 citation statements)

References 168 publications

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“…In the absence of inflammation (as in the healthy control), NF- κβ binds to its inhibitor protein I κβ , to be conserved in an inactive low expressive form [ 100 ].…”

Section: Discussionmentioning

confidence: 99%

CanToxoplasma gondiiPave the Road for Dementia?

Saftawy

Amin

Sabry

et al. 2020

Journal of Parasitology Research

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Dementia is an ominous neurological disease. Scientists proposed a link between its occurrence and the presence of Toxoplasma gondii (T. gondii). The long-term sequels of anti-Toxoplasma premunition, chiefly dominated by TNF-α, on the neurons and their receptors as the insulin-like growth factor-1 receptor (IGF-1R), which is tangled in cognition and synaptic plasticity, are still not clear. IGF-1R mediates its action via IGF-1, and its depletion is incorporated in the pathogenesis of dementia. The activated TNF-α signaling pathway induces NF-κβ that may induce or inhibit neurogenesis. This study speculates the potential impact of anti-Toxoplasma immune response on the expression of IGF-1R in chronic cerebral toxoplasmosis. The distributive pattern of T. gondii cysts was studied in association with TNF-α serum levels, the in situ expression of NF-κβ, and IGF-1R in mice using the low virulent ME-49 T. gondii strain. There was an elevation of the TNF-α serum level (p value ≤ 0.004) and significant upsurge in NF-κβ whereas IGF-1R was of low abundance (p value < 0.05) compared to the controls. TNF-α had a strong positive correlation with the intracerebral expression of NF-κβ (r value ≈ 0.943, p value ≈ 0.005) and a strong negative correlation to IGF-1R (r value -0.584 and -0.725 for area% and O.D., respectively). This activated TNF-α/NF-κβ keeps T. gondii under control at the expense of IGF-1R expression, depriving neurons of the effect of IGF-1, the receptor’s ligand. We therefore deduce that T. gondii immunopathological reaction may be a road paver for developing dementia.

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“…In the absence of inflammation (as in the healthy control), NF- κβ binds to its inhibitor protein I κβ , to be conserved in an inactive low expressive form [ 100 ].…”

Section: Discussionmentioning

confidence: 99%

CanToxoplasma gondiiPave the Road for Dementia?

Saftawy

Amin

Sabry

et al. 2020

Journal of Parasitology Research

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“…Numerous molecular targets of resveratrol were reported, most important follow. Resveratrol activates AMPK [ 119 , 120 ]; downregulates NF-κB [ 121 , 122 ] thus impacting numerous cellular processes, particularly inflammatory responses, cellular growth, and apoptosis [ 123 , 124 ]; and downregulates PI3K/Akt and mTOR pathway [ 125 , 126 ], involved in regulating a variety of processes including insulin signaling, cell proliferation, and survival [ 127 ]. Resveratrol can modulate mitochondrial calcium, increase the efficacy of chemotherapeutic agents, target cancer stem cells, alleviate inflammation associated with tumors, and promote the elimination of impaired mitochondria through mitophagy [ 128 , 129 ].…”

Section: Senotherapeuticsmentioning

confidence: 99%

Mini-encyclopedia of mitochondria-relevant nutraceuticals protecting health in primary and secondary care—clinically relevant 3PM innovation

Golubnitschaja,

Kapinova,

Sargheini

et al. 2024

EPMA Journal

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Despite their subordination in humans, to a great extent, mitochondria maintain their independent status but tightly cooperate with the “host” on protecting the joint life quality and minimizing health risks. Under oxidative stress conditions, healthy mitochondria promptly increase mitophagy level to remove damaged “fellows” rejuvenating the mitochondrial population and sending fragments of mtDNA as SOS signals to all systems in the human body. As long as metabolic pathways are under systemic control and well-concerted together, adaptive mechanisms become triggered increasing systemic protection, activating antioxidant defense and repair machinery. Contextually, all attributes of mitochondrial patho-/physiology are instrumental for predictive medical approach and cost-effective treatments tailored to individualized patient profiles in primary (to protect vulnerable individuals again the health-to-disease transition) and secondary (to protect affected individuals again disease progression) care. Nutraceuticals are naturally occurring bioactive compounds demonstrating health-promoting, illness-preventing, and other health-related benefits. Keeping in mind health-promoting properties of nutraceuticals along with their great therapeutic potential and safety profile, there is a permanently growing demand on the application of mitochondria-relevant nutraceuticals. Application of nutraceuticals is beneficial only if meeting needs at individual level. Therefore, health risk assessment and creation of individualized patient profiles are of pivotal importance followed by adapted nutraceutical sets meeting individual needs. Based on the scientific evidence available for mitochondria-relevant nutraceuticals, this article presents examples of frequent medical conditions, which require protective measures targeted on mitochondria as a holistic approach following advanced concepts of predictive, preventive, and personalized medicine (PPPM/3PM) in primary and secondary care.

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“…The past two decades have witnessed much interest in exploring dietary polyphenols, especially catechol-type molecules as inhibitors of NF-κB for the treatment of chronic inflammation and cancer. − For example, with piceatannol ( trans -3,3′,4,5′-tetrahydroxystilbene), it is a dietary catechol found in peanuts, Vitis amurensis, Vaccinium berries, and red wine, and also an analogue structurally related to resveratrol (RES, trans -3,4′,5-trihydroxystilbene,Scheme ). , Compared with RES, piceatannol is slowly metabolized as can be deduced from its rat plasma level measurement and exhibits stronger inhibitory activity against NF-κB signaling and inflammation. − …”

Section: Introductionmentioning

confidence: 99%

Inhibiting NF-κB-Mediated Inflammation by Catechol-Type Diphenylbutadiene via an Intracellular Copper- and Iron-Dependent Pro-Oxidative Role

Dai

Zheng

et al. 2020

J. Agric. Food Chem.

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Chronic inflammation mediated by nuclear factor-κB (NF-κB) plays a crucial role in the development of cancer. As part of our continuous efforts placed on investigating anticancer mechanisms of dietary catechols, we further applied catechol-type diphenylbutadiene (3,4-DHB) as a model molecule to probe whether it inhibits inflammation by its pro-oxidative role. Employing lipopolysaccharide-stimulated RAW264.7 cells as a model of inflammation, we validated that benefiting from its catechol moiety, 3,4-DHB inhibited significantly the LPS-induced formation of NO (11.48 ± 0.39 μM) compared with the only LPS-stimulated group (31.8 ± 1.78 μM) with an inhibitory rate of 64% at 5 μM, expression of iNOS and COX-2 proteins, phosphorylation of IkB kinase and IkBα, and nuclear translocation of NF-κB. Noticeably, its inhibitory activity against the NF-κB-mediated inflammation can be obviously revised by pretreatment of the cells with dithiothreitol (a quencher of both electrophilic o-quinone and ROS), neocuproine (a specific chelating agent for copper ions), and deferoxamine (a specific chelating agent for iron ions). The above results support that depending on intracellular copper and iron ions, 3,4-DHB, a pro-electrophile, can be converted into its corresponding o-quinone electrophile together with the generation of ROS, a pro-oxidative event that mediates its inhibitory activity against NF-κB signaling and inflammation. The copper- and iron-dependent inhibition against inflammation supports that dietary catechols are probably pro-oxidative anti-inflammatory agents.

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Inhibitors of transcription factor nuclear factor-kappa beta (NF-κβ)-DNA binding

Cited by 10 publications

References 168 publications

CanToxoplasma gondiiPave the Road for Dementia?

CanToxoplasma gondiiPave the Road for Dementia?

Mini-encyclopedia of mitochondria-relevant nutraceuticals protecting health in primary and secondary care—clinically relevant 3PM innovation

Inhibiting NF-κB-Mediated Inflammation by Catechol-Type Diphenylbutadiene via an Intracellular Copper- and Iron-Dependent Pro-Oxidative Role

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