Relationship between the structures of flavonoids and their NF-κB-dependent transcriptional activities

Shin, Soon Young; Woo, Yoonkyung; Hyun, Jiye; Yong, Yeonjoong; Koh, Dongsoo; Lee, Young Han; Lim, Yoongho

doi:10.1016/j.bmcl.2011.08.077

Cited by 50 publications

(34 citation statements)

References 29 publications

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“…Fisetin, showing the greatest ability to activate AMPK, is a well-documented AMPK activator (Shin et al 2011). However, the AMPK activation ability of the second ranked flavonoid among the test compounds, kaempferide, has not been reported.…”

Section: Resultsmentioning

confidence: 98%

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Flavonoids activating adenosine monophosphate-activated protein kinase

Yong

Shin

Jung

et al. 2015

J Korean Soc Appl Biol Chem

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Eighteen flavonoids were tested as adenosine monophosphate-activated protein kinase (AMPK) activators. The AMPK activation induced by kaempferide was 1.75 times better than the value obtained at 100 % AMPK phosphorylation. Western blotting analysis of kaempferide demonstrated that it increased the phosphorylation of AMPK in vitro. In silico docking results carried out to elucidate the binding mode between kaempferide and AMPK showed the docking pose of kaempferide in the binding site of AMPK was similar to that of the substrate contained in the crystallographic structure of AMPK. Flavonoids, including kaempferide, are promising potential AMPK activators.

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Section: Resultsmentioning

confidence: 98%

“…1), decrease activity in sinensetin. Further experiments for quantitative SAR are required (Shin et al 2011).…”

Section: Resultsmentioning

confidence: 99%

Flavonoids activating adenosine monophosphate-activated protein kinase

Yong

Shin

Jung

et al. 2015

J Korean Soc Appl Biol Chem

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“…All calculations were carried out on an Intel Core 2 Quad Q6600 (2.4 GHz) Linux PC with the molecular modeling package SYBYL 7.3 (Tripose, St. Louis, MO, USA) [11]. The 3D structures of synthetic polyphenols 10 – 19 were constructed based on the X-ray crystallographic structure of 2′,3,5-trimethoxychalcone, which was determined by the authors (Figure S3A) [30].…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, the test set can be used to validate whether the QSAR models in this experiment are reliable. The QSAR calculations were performed using CoMFA and CoMSIA and the experimental procedures followed reported methods [11]. …”

Section: Methodsmentioning

confidence: 99%

Structural Properties of Polyphenols Causing Cell Cycle Arrest at G1 Phase in HCT116 Human Colorectal Cancer Cell Lines

Shin

Yoon

Ahn

et al. 2013

IJMS

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Plant-derived polyphenols are being tested as chemopreventive agents; some polyphenols arrest the cell cycle at G1 phase, whereas others inhibit cell cycle proliferation at G2/M phase. Therefore, polyphenols have been proposed to inhibit cell cycle progression at different phases via distinct mechanisms. Indeed, our previous studies showed that small structural differences in polyphenols cause large differences in their biological activities; however, the details of the structural properties causing G1 cell cycle arrest remain unknown. In this study, we prepared 27 polyphenols, including eight different scaffolds, to gain insight into the structural conditions that arrest the cell cycle at G1 phase in a quantitative structure–activity relationship study. We used cell cycle profiles to determine the biophores responsible for G1 cell cycle arrest and believe that the biophores identified in this study will help design polyphenols that cause G1 cell cycle arrest.

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“…The cells were then fixed and permeabilized as described previously (Shin et al, 2011b). Antibodies against Iba1 (microglial marker) or phospho-p65/RelA (Ser468) were added for 2 h, and then an Alexa Fluor 488-conjugated (Invitrogen; green signal for Ibai) or Alexa Fluor 555-conjugated (Invitrogen; red signal for phospho-RelA) secondary antibody, respectively, was added for 30 min.…”

Section: Methodsmentioning

confidence: 99%

A new synthetic chalcone derivative, 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139), suppresses the Toll-like receptor 4-mediated inflammatory response through inhibition of the Akt/NF-κB pathway in BV2 microglial cells

et al. 2012

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Microglial cells are the resident innate immune cells that sense pathogens and tissue injury in the central nervous system (CNS). Microglial activation is critical for neuroinflammatory responses. The synthetic compound 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139) is a novel chalcone-derived compound. In this study, we investigated the effects of DK-139 on Toll-like receptor 4 (TLR4)-mediated inflammatory responses in BV2 microglial cells. DK-139 inhibited lipopolysaccharide (LPS)-induced TLR4 activity, as determined using a cell-based assay. DK-139 blocked LPS-induced phosphorylation of IκB and p65/RelA NF-κB, resulting in inhibition of the nuclear translocation and trans-acting activity of NF-κB in BV2 microglial cells. We also found that DK-139 reduced the expression of NF-κB target genes, such as those for COX-2, iNOS, and IL-1β, in LPS-stimulated BV2 microglial cells. Interestingly, DK-139 blocked LPS-induced Akt phosphorylation. Inhibition of Akt abrogated LPS-induced phosphorylation of p65/RelA, while overexpression of dominant-active p110CAAX enhanced p65/RelA phosphorylation as well as iNOS and COX2 expression. These results suggest that DK-139 exerts an anti-inflammatory effect on microglial cells by inhibiting the Akt/IκB kinase (IKK)/NF-κB signaling pathway.

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Relationship between the structures of flavonoids and their NF-κB-dependent transcriptional activities

Cited by 50 publications

References 29 publications

Flavonoids activating adenosine monophosphate-activated protein kinase

Flavonoids activating adenosine monophosphate-activated protein kinase

Structural Properties of Polyphenols Causing Cell Cycle Arrest at G1 Phase in HCT116 Human Colorectal Cancer Cell Lines

A new synthetic chalcone derivative, 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139), suppresses the Toll-like receptor 4-mediated inflammatory response through inhibition of the Akt/NF-κB pathway in BV2 microglial cells

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