Nuclear Factor .KAPPA.B Inhibition by Dibenzoylmethane Derivatives

Matsuura, Nobuo; Murakami, Rika; Katayama, Tomoyuki; Hibino, Satoshi; Choshi, Tominari; Yamada, Masashi

doi:10.1248/jhs.55.311

Cited by 10 publications

(9 citation statements)

References 5 publications

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“…Echinalides A-G (1-7) were subjected to this assay system at 20 µM and 5 µM, and the value was determined from at least three individual experiments. Echinalides C (3) and D (4) showed potent activities [for C (3), 20 µM: 100%, 5 µM: 70% inhibition and for D (4), 20 µM: 100%, 5 µM: 78% inhibition] nearly equivalent to that of parthenolide 26) [5 µM: 98%], a known potent inhibitor of NF-κB; the inhibitory activities of echinalides E (5), F (6) and G (7) [for E (5), 20 µM: 100%, 5 µM: 32%, for F (6), 20 µM: 100%, 5 µM: 16%, for G (7), 20 µM: 100%, 5.0 µM: 27% inhibition] were weaker than that of parthenolide. In contrast, inhibitory activity was not observed for echinalides A (1) and B (2) [for A (1); 20 µM: 0%, for B (2), 20 µM: 23% inhibition].…”

Section: Resultsmentioning

confidence: 99%

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New Cassane-Type Diterpenoids of Caesalpinia echinata (Leguminosae) Exhibiting NF-κB Inhibitory Activities

Mitsui

Ishihara

Hayashi

et al. 2014

CHEMICAL & PHARMACEUTICAL BULLETIN

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Seven new cassane-type diterpenoids, echinalides A-G (1-7), were isolated from the stem of Caesalpinia echinata LAM. (Leguminosae). The structures were established on the basis of their chemical properties and spectroscopic evidence, including two dimensional (2D)-NMR analysis. These compounds were assessed for inhibitory activity against nuclear factor κB (NF-κB). Echinalides C and D, in particular, significantly inhibited NF-κB-responsive reporter gene expression at 5.0 µM, an effect almost equivalent to that of parthenolide, a known potent inhibitor of NF-κB.

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Section: Resultsmentioning

confidence: 99%

“…26) In brief, 0.5×10 4 cells were seeded in a 96-well tissue culture plate. After 2 h, an aliquot of a test sample solution was added to each well.…”

Section: Methodsmentioning

confidence: 99%

New Cassane-Type Diterpenoids of Caesalpinia echinata (Leguminosae) Exhibiting NF-κB Inhibitory Activities

Mitsui

Ishihara

Hayashi

et al. 2014

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…16) In brief, 0.5×10 4 cells were seeded into a 96-well tissue culture plate. After 2 h, an aliquot of a test sample solution was added to each well.…”

Section: Assay For Nf-κb Inhibitory Activitymentioning

confidence: 99%

Culcitiolides E–J, Six New Eremophilane-Type Sesquiterpene Derivatives from Senecio culcitioides

Mitsui

Hayashi

Kawai

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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Culcitiolides E-J (1-6), six new eremophilane-type sesquiterpenes, were isolated from the stem of Senecio culcitioides Sch. Bip. (Asteraceae). The structures were determined by detailed NMR spectral analysis. The inhibitory activities of these compounds against nuclear factor κB (NF-κB)-dependent gene expression were assessed. Culcitiolides E, H, and I potently inhibited NF-κB-induced gene expression at 20 µm.Key words Senecio culcitioides; eremophilane; culcitiolide; nuclear factor κB Senecio culcitioides Sch. Bip. is distributed throughout the Peruvian Andes in South America at an altitude of 4500-5000 m. S. culcitioides belongs to the family Asteraceae and has been used as a traditional folk medicine to treat cough, bronchitis and asthma.1-3) Nuclear factor κB (NF-κB) is a transcription factor and functions as a key regulatory element in inflammatory and immune responses and in cancer. During our search for new classes of inhibitors of NF-κB derived from natural products, we previously isolated culcitiolides A-D, eremophilane-type sesquiterpenoids from the stem of the previously uninvestigated plant S. culcitioides, and we showed that culcitiolides C and D are potent NF-κB inhibitors. 4) Our continuous effort to identify NF-κB inhibitors in S. culcitioides led to the isolation of six new eremophilane-type sesquiterpenoids exhibiting potent NF-κB inhibitory activity. Herein, we describe the isolation and structural elucidation of culcitiolides E-J and the evaluation of their inhibitory activities against NF-κB-dependent gene expression.

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“…15) In brief, 0.5ϫ 10 4 cells of HeLa NF-kB -3 were seeded on a 96-well tissue culture plate. After 2 h, aliquots of test sample solution (20, 200 mM) were added into each well.…”

Section: Analysis Of the Protective Effects Against Er Stressmentioning

confidence: 99%

“…Moreover, some DBM derivatives inhibited NF-kB activity. 15) However, it remains unclear whether DBM derivatives that have NF-kB inhibitory activity are effective against colitis.…”

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confidence: 99%

Efficacy of Dibenzoylmethane Derivatives in Protecting against Endoplasmic Reticulum Stress and Inhibiting Nuclear Factor Kappa B on Dextran Sulfate Sodium Induced Colitis in Mice

Murakami¹,

Uchida²,

Hori

et al. 2010

Biological & Pharmaceutical Bulletin

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Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, comprises a group of multifactorial disorders of unknown etiology but has a high incidence that is widely distributed throughout the human population.1) Although the etiology of IBD is not clear at present, recent studies suggest that IBD is a disorder involving activation of leukocytes (macrophages, lymphocytes, and neutrophils) and their infiltration into the inflamed intestine. [2][3][4][5] Enhanced endoplasmic reticulum (ER) stress has been implicated in various pathological situations including inflammation. Several reports have shown that the ER stress response is induced in association with the development of IBD. Bertlotti et al. 6) reported that when dextran sulfate sodium (DSS) was administered to mice deficient in the eukaryotic inositol-requiring transmembrane kinase-endoribonuclease-1b (IRE1b) gene to induce colitis, the time to onset was shorter (early onset) than that in the wild species. The IRE1b gene is known to be involved in signal transmission in ER stress. In addition, Kaser et al. 7) reported that the transcription factor X-box binding protein 1 (XBP1), which is an important key to ER stress response, is involved in the genetic risk of onset of IBD in humans. These findings suggest a possible correlation between IBD and ER stress.We reported that dantrolene, an antagonist of ryanodine receptors in the ER, and some antioxidants such as a-tocopherol, partly prevented tunicamycin-induced cell death in F9 homocystein-induced ER protein null cells.8) Using this cell line, our group and others have reported that 103 plantderived compounds 9,10) and 200 synthetic compounds including dibenzoylmethane (DBM) derivatives, 11) carbazole derivatives, 12) and pyrimidine derivatives were screened previously, and some DBM derivatives improved cell viability after tunicamycin treatment at a level similar to that achieved by dantrolene in F9 Herp null cells.11) However, it remains unclear whether DBM derivatives that have protective effects against ER stress are effective against colitis.Nuclear factor kB (NF-kB) is a dimeric transcription factor that induces the expression of genes involved in the inflammatory process. Activation of NF-kB has been observed in the mucosa of patients with ulcerative colitis, 13) and butyrate has been shown to inhibit NF-kB activation in lamina propia macrophages of patients with ulcerative colitis.14) Previously, our group reported that HeLa NF-kB -3 cells, which are stable transformants with a NF-kB response element, obtained a reporter gene. These cells showed an approximately 6-fold higher activation of NF-kB with tumor necrosis factor alpha (TNF-a) stimulation. Moreover, some DBM derivatives inhibited NF-kB activity.15) However, it remains unclear whether DBM derivatives that have NF-kB inhibitory activity are effective against colitis.Zhang and Kaufman suggest that an enhanced ER stress response contributed to the progression of inflammation through the activation of NF-kB. 16)T...

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Nuclear Factor .KAPPA.B Inhibition by Dibenzoylmethane Derivatives

Cited by 10 publications

References 5 publications

New Cassane-Type Diterpenoids of <i>Caesalpinia echinata</i> (Leguminosae) Exhibiting NF-κB Inhibitory Activities

New Cassane-Type Diterpenoids of <i>Caesalpinia echinata</i> (Leguminosae) Exhibiting NF-κB Inhibitory Activities

Culcitiolides E–J, Six New Eremophilane-Type Sesquiterpene Derivatives from <i>Senecio culcitioides</i>

Efficacy of Dibenzoylmethane Derivatives in Protecting against Endoplasmic Reticulum Stress and Inhibiting Nuclear Factor Kappa B on Dextran Sulfate Sodium Induced Colitis in Mice

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