Curcumin is a potent DNA hypomethylation agent

Liu, Zhongfa; Xie, Zhiliang; Jones, W.P.; Pavlovicz, Ryan E.; Liu, Shujun; Yu, Jianhua; Li, Pui kai; Lin, Jiayuh; Fuchs, James R.; Marcucci, Guido; Li, Chenglong; Chan, Kenneth K.

doi:10.1016/j.bmcl.2008.12.041

Cited by 293 publications

(208 citation statements)

References 14 publications

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“…CUR has been demonstrated to exert its demethylation effect through covalent binding to the catalytic thiolate of C1226 of DNMT1, which was further validated by the inhibitory effect of CUR on M.Sss1 activity with an IC50 of 30 nM (24). Several studies have also reported that CUR could inhibit the activity or expression of DNMTs (40,42).…”

Section: Inhibition Of Akt/nf-κb Signaling By Cur Is Associated With mentioning

confidence: 82%

“…Now, it is showing promising results in clinical trials as a potential therapy for inflammatory and malignant diseases (21,22). Besides the roles of CUR in anti-inflammation and anti-oxidative stress, accumulating evidence indicates that CUR is a potential epigenetic inhibitor, particularly possessing inhibitory effects on DNA methyltransferases (DNMTs) with low concentration (23,24). Moreover, the potential of CUR analogues EF31 and UBS109 as epigenetic modifier and anti-carcinogenic agent is also being delineated (25,26).…”

Section: Introductionmentioning

confidence: 99%

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Curcumin Inhibits the AKT/NF-κB Signaling via CpG Demethylation of the Promoter and Restoration of NEP in the N2a Cell Line

Deng

Wang

et al. 2014

AAPS J

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Abstract. Curcumin (CUR), a non-toxic polyphenol from Curcuma longa, has been investigated as a potential therapy with anti-inflammatory and anti-oxidative effects for Alzheimer's disease (AD), which depicts features of chronic inflammatory environment resulting in cellular death. However, it remains largely unknown whether the anti-inflammatory effect of CUR in AD is associated with its property of CpG demethylation, which is another function of CUR with the most research interest during recent years. Neprilysin (NEP, EP24.11), a zinc-dependent metallopeptidase expressed relatively low in the brain, is emerging as a potent inhibitor of AKT/Protein Kinase B. In addition, hypermethylated promoter of NEP has been reported to be associated with decreases in NEP expression. In the present study, using bisulfite-sequencing PCR (BSP) assay, we showed that the CpG sites in NEP gene were hypermethylated both in wild-type mouse neuroblastoma N2a cells (N2a/wt) and N2a cells stably expressing human Swedish mutant amyloid precursor protein (APP) (N2a/APPswe) associated with familial early onset AD. CUR treatment induced restoration of NEP gene via CpG demethylation. This CUR-mediated upregulation of NEP expression was also concomitant with the inhibition of AKT, subsequent suppression of nuclear transcription factor-κB (NF-κB) and its downstream pro-inflammatory targets including COX-2, iNOS in N2a/APPswe cells. This study represents the first evidence on a link between CpG demethylation effect on NEP and anti-inflammation ability of CUR that may provide a novel mechanistic insight into the anti-inflammatory actions of CUR as well as new basis for using CUR as a therapeutic intervention for AD.

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Section: Inhibition Of Akt/nf-κb Signaling By Cur Is Associated With mentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Curcumin Inhibits the AKT/NF-κB Signaling via CpG Demethylation of the Promoter and Restoration of NEP in the N2a Cell Line

Deng

Wang

et al. 2014

AAPS J

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“…DNMT inhibitory activity is associated with reactivation of epigenetically silenced genes such as p16, RARb, MGMT, MLH1, BTG3 and GSTP1 in human cancer cells, suggesting a possible alternate phytotherapeutic modality by targeting epigenetically silenced tumor suppressor genes through dietary polyphenols [104,105]. Curcumin has also been reported to exhibit epigenetic modulation in cancer cells by histone acetyltransferase (HAT) and DNMT1 inhibition activities [106][107][108][109]. Intake of polyphenols rich nutraceuticals, therefore, protects human gut from malignant transformation.…”

Section: Sodium Butyratementioning

confidence: 99%

Nutraceuticals as Chemopreventive and Therapeutic agents in Gut Associated Pathogenesis

Ahmad¹,

Nasiruddin²,

Khan³

et al. 2016

Biochem Anal Biochem

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Nutraceuticals have gained great insights in recent years due to their therapeutic implications. Secondary metabolites like glutamate, flavonoids, polyphenols and terpenoids are widespread in nature and are part of human diet. Polysaccharides of prebiotic nature are used both as therapeutic and prophylactic agents. These nutraceuticals in recent times have been reported to posses great potential to reduce antigenic and oxidative pressure in the human gut. Antioxidant rich diet is a potential therapeutic agent against reactive oxygen species induced pathogenesis. Epegenetic compounds present in antioxidant and prebiotics rich nutraceuticals mitigate and remove the causative factors associated with pathogenesis. Flavonoids and polyphenols exhibit antioxidant properties and have been recognized as potential gastroprotective agents and epigenetic modulators as well. Triterpenoids such as cucurbitacin is reported to posses anticancer activities. Glutamate is an enteric neurotransmitter that is used in improving neonatal gut function. This review comprehensively summarizes the current knowledge of gut modulating nutraceuticals which ultimately can play its role from prophylaxis of gut to its therapeutics by employing various macro and micro molecular pathways.

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“…A few other reports also supported that curcumin and its analogues could bind to various enzymes which includes human immunodefi Molecular docking analysis of curcumin analogues as human Molecular docking analysis of curcumin analogues as human Molecular docking analysis of curcumin analogues as human Molecular docking analysis of curcumin analogues as human neutrophil elastase inhibitors neutrophil elastase inhibitors neutrophil elastase inhibitors neutrophil elastase inhibitors ciency virus type-I protease (Sui et al, 1993), cyclooxygenase-1 (Selvam et al, 2005), DNA polymerase λ (Takeuchi et al, 2006), platelet-12-lipoxygenase (Jankun et al, 2006), cyclooxygenase-2 (Padhye et al, 2009), DNA methyl transferase-1 (Liu et al, 2009), xanthine oxidase (Shen andJi, 2009), dipeptydyl peptidase-4 (Istyastono, 2009), glycogen synthase kinase-3β (Bustanji et al, 2009), ribonuclease A (Sahoo et al, 2009), glyoxalase-I (Liu et al, 2010), protein kinase C (Majhi et al, 2010) and matrix metalloproteinases (Girija et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Molecular docking analysis of curcumin analogues as human neutrophil elastase inhibitors

Narayanaswamy¹,

Lam²,

Abas³

et al. 2014

Bangladesh J Pharmacol

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In the present study, we aimed to dock 17 different ligands of curcumin analogues with that of human neutrophil elastase. Molecular descriptors analysis using Molinspiration online tool was carried out including investigation on human neutrophil elastase putative binding sites using Discovery Studio. The molecular physicochemical analysis revealed that all of the curcumin analogues complied well with the five rules of thumb. With regard to bioactivity score, compound 17 has exhibited least score towards nuclear receptor ligand (0.05) and enzyme inhibitor (0.10) compared to all other ligands. Compounds 2, 4 and 13 exhibited the maximum interaction energy (-40 kcal/ mol). Interestingly, seven compounds namely 3, 11-14, 16 and 17 interacted well with Arg147 amino acid residue. The present study outcomes therefore might provide new insight in understanding these 17 curcumin analogues as potential candidates for human neutrophil elastase inhibitory agents. Article Info

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Curcumin is a potent DNA hypomethylation agent

Cited by 293 publications

References 14 publications

Curcumin Inhibits the AKT/NF-κB Signaling via CpG Demethylation of the Promoter and Restoration of NEP in the N2a Cell Line

Curcumin Inhibits the AKT/NF-κB Signaling via CpG Demethylation of the Promoter and Restoration of NEP in the N2a Cell Line

Nutraceuticals as Chemopreventive and Therapeutic agents in Gut Associated Pathogenesis

Molecular docking analysis of curcumin analogues as human neutrophil elastase inhibitors

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