The anti-inflammatory effects of E -α-( p -methoxyphenyl)-2′,3,4,4′-tetramethoxychalcone are mediated via HO-1 induction

Kaufmann, Kai; Gothwal, Monika; Schallner, Nils; Ulbrich, Felix; Rücker, Hannelore-Maria; Amslinger, Sabine; Goebel, Ulrich

doi:10.1016/j.intimp.2016.03.018

Cited by 11 publications

(6 citation statements)

References 53 publications

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“…Accumulating evidence suggests that chalcones regulate inflammatory responses via induction of anti-inflammatory genes. For example, synthetic chalcone derivatives suppressed LPS-stimulated nitric oxide production and down-regulated various inflammatory cytokines through heme oxygenase-1 (HO-1) induction ( Kaufmann et al ., 2016 ), indicating that HO-1 could partly underlie anti-inflammatory and anti-oxidant properties of chalcones. In the present study, to further elucidate the molecular mechanisms underlying the anti-inflammatory activity of YJI-7, we investigated its effect on HO-1 induction.…”

Section: Discussionmentioning

confidence: 99%

“…Chalcones suppress the transcriptional activities of AP-1, NF-κB and STAT3, and inhibit the expression of various pro-inflammatory mediators, including TNF-α, interleukins, cell adhesion molecules and cyclo-oxygenase-2 ( Kontogiorgis et al ., 2008 ; Yadav et al ., 2011 ; Zhang et al ., 2014 ). Furthermore, chalcones activate anti-inflammatory mechanisms, e.g., heme oxygenase-1 induction ( Kim et al ., 2014 ; Kaufmann et al ., 2016 ). Based on previous reports, there is a growing appreciation that chalcone and its synthetic derivatives are promising for the treatment of the various diseases associated with inflammation.…”

Section: Introductionmentioning

confidence: 99%

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YJI-7 Suppresses ROS Production and Expression of Inflammatory Mediators via Modulation of p38MAPK and JNK Signaling in RAW 264.7 Macrophages

Magar

Pun

et al. 2018

Biomolecules & Therapeutics

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Chalcone, (2E)-1,3-Diphenylprop-2-en-1-one, and its synthetic derivatives are known to possess anti-oxidative and anti-inflammatory properties. In the present study, we prepared a novel synthetic chalcone compound, (E)-1-(4-hydroxyphenyl)-3-(2-(trifluoromethoxy)phenyl)prop-2-en-1-one name (YJI-7), and investigated its inhibitory effects on endotoxin-stimulated production of reactive oxygen species (ROS) and expression of inflammatory mediators in macrophages. We demonstrated that treatment of RAW 264.7 macrophages with YJI-7 significantly suppressed lipopolysaccharide (LPS)-stimulated ROS production. We also found that YJI-7 substantially decreased NADPH oxidase activity stimulated by LPS, indicating that YJI-7 regulates ROS production via modulation of NADPH oxidase in macrophages. Furthermore, YJI-7 strongly inhibited the expression of a number of inflammatory mediators in a gene-selective manner, suggesting that YJI-7 possesses potent anti-inflammatory properties, as well as anti-oxidative activity. In continuing experiments to investigate the mechanisms that could underlie such biological effects, we revealed that YJI-7 suppressed phosphorylation of p38MAPK and JNK stimulated by LPS, whereas no significant effect on ERK was observed. Furthermore, LPS-stimulated production of ROS, activation of NADPH oxidase and expression of inflammatory mediators were markedly suppressed by treatment with selective inhibitor of p38MAPK (SB203580) and JNK (SP600125). Taken together, these results demonstrated that YJI-7, a novel synthetic chalcone derivative, suppressed LPS-stimulated ROS production via modulation of NADPH oxidase and diminished expression of inflammatory mediators, at least in part, via down-regulation of p38MAPK and JNK signaling in macrophages.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

YJI-7 Suppresses ROS Production and Expression of Inflammatory Mediators via Modulation of p38MAPK and JNK Signaling in RAW 264.7 Macrophages

Magar

Pun

et al. 2018

Biomolecules & Therapeutics

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“…In this regard, the cytoprotective effect of 30 may be partly related to both the non-toxic activation and inhibition of the Nrf2/HO-1 and NF-κB pathways, respectively. The authors also evaluated the anti-inflammatory activity of 30 in RAW264.7 cells treated with LPS [ 58 ]. The results confirmed the ability of 30 to control several inflammatory parameters including the release of proinflammatory cytokines IL-1β, IL-6 and monocyte chemoattractant protein 1 (MCP-1), remarkably through the activation of Nrf2/HO-1.…”

Section: Targeting the Nrf2 Pathway By Synthetic Chalconesmentioning

confidence: 99%

The Keap1/Nrf2-ARE Pathway as a Pharmacological Target for Chalcones

et al. 2018

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Chalcones have shown a broad spectrum of biological activities with clinical potential against various diseases. The biological activities are mainly attributed to the presence in the chalcones of the α,β-unsaturated carbonyl system, perceived as a potential Michael acceptor. Chalcones could activate the Kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway through a Michael addition reaction with the cysteines of Keap1, which acts as a redox sensor and negative regulator of Nrf2. This modification allows the dissociation of Nrf2 from the cytoplasmic complex with Keap1 and its nuclear translocation. At this level, Nrf2 binds to the antioxidant response element (ARE) and activates the expression of several detoxification, antioxidant and anti-inflammatory genes as well as genes involved in the clearance of damaged proteins. In this regard, the Keap1/Nrf2–ARE pathway is a new potential pharmacological target for the treatment of many chronic diseases. In this review we summarize the current progress in the study of Keap1/Nrf2–ARE pathway activation by natural and synthetic chalcones and their potential pharmacological applications. Among the pharmacological activities highlighted, anti-inflammatory activity was more evident than others, suggesting a multi-target Michael acceptor mechanism for the chalcones involving key regulators of the Nrf2 and nuclear factor- κB (NF-κB) pathways.

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“…Recent reports, have also shown that the synthetic chalcones E‐α‐( p ‐methoxy phenyl)‐2′3,4,4′‐tetra methoxy chalcone and 2,3‐dimethoxy‐2′‐hydroxy chalcone having methoxy groups at para ‐ and ortho ‐ positions respectively exerts anti‐inflammatory activity. Molecular docking studies exposed that its compact skeleton is the basic reason of how it holds strong contacts with the important amino acid side chains inside the active site as well as adjoining sites of the enzyme thus preventing its pro‐inflammatory role.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Characterization, Docking and Study of Inhibitory Action of Some Novel C-Alkylated Chalcones on 5-LOX Enzyme

et al. 2017

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A series of C‐alkylated chalcones on ring ‘B’ of C6‐C3‐C6 system of the basic flavonoid skeleton were synthesized by taking different alkyl substituted aldehydes by conventional approaches. The compounds (5 a‐l) were obtained by condensing di‐O‐methylated phloroacetophenone with various alkylated (methyl, di‐methyl, ethyl and n‐propyl) substituted aromatic aldehydes (4 a‐l) and characterized by different spectroscopic methods (IR, NMR, LC–MS and elemental analysis) and further studied their inhibitory action on 5‐lipoxygenase (5‐LOX) enzyme. The compounds (E)‐3‐(4‐ethoxy‐5‐methoxy‐2‐methylphenyl)‐1‐(2‐hydroxy‐4,6‐dimethoxyphenyl) prop‐2‐en‐1‐one (5 k), (E)‐3‐(2,4‐dimethoxy‐5‐methylphenyl)‐1‐(2‐hydroxy‐4,6‐dimethoxy phenyl)prop‐2‐en‐1‐one (5 i), (E)‐3‐(4,5‐dimethoxy‐2‐methylphenyl)‐1‐(2‐hydroxy‐4,6‐dimethoxyphenyl)prop‐2‐en‐1‐one (5 j), and (E)‐1‐(2‐hydroxy‐4,6‐dimethoxyphenyl)‐3‐(2‐methoxy‐4,5‐dimethylphenyl)prop‐2‐en‐1‐one (5 l) showed a significant 5‐LOX enzyme inhibitory action with IC50 ranging between 49.1 and 52.3 μM, whereas positive control curcumin exhibited IC50 of 22 μM. The molecular docking simulation study revealed that the compounds were well accommodated in the allosteric site of the enzyme, 5‐LOX.

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The anti-inflammatory effects of E -α-( p -methoxyphenyl)-2′,3,4,4′-tetramethoxychalcone are mediated via HO-1 induction

Cited by 11 publications

References 53 publications

YJI-7 Suppresses ROS Production and Expression of Inflammatory Mediators via Modulation of p38MAPK and JNK Signaling in RAW 264.7 Macrophages

YJI-7 Suppresses ROS Production and Expression of Inflammatory Mediators via Modulation of p38MAPK and JNK Signaling in RAW 264.7 Macrophages

The Keap1/Nrf2-ARE Pathway as a Pharmacological Target for Chalcones

Synthesis, Characterization, Docking and Study of Inhibitory Action of Some Novel C-Alkylated Chalcones on 5-LOX Enzyme

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