Inhibition of airway MUC5AC mucin production and gene expression induced by epidermal growth factor or phorbol ester by glycyrrhizin and carbenoxolone

Lee, Hyun Jae; Lee, Su Yel; Bae, Heung Seog; Kim, Jang-Hyun; Chang, Gyu Tae; Seok, Jeong Ho; Lee, Choong Jae

doi:10.1016/j.phymed.2010.11.003

Cited by 13 publications

(14 citation statements)

References 19 publications

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“…We have tried to investigate the possible activities of some flavonoids on mucin production (secretion) from airway epithelial cells. As a result of our trial, we previously reported that several compounds affected mucin production and/or secretion from airway epithelial cells4,5,6,7. According to folk medicine, Scutellaria baicalensis Georgi has been used for regulating airway allergic and inflammatory diseases8.…”

Section: Introductionmentioning

confidence: 85%

Apigenin and Wogonin Regulate Epidermal Growth Factor Receptor Signaling Pathway Involved in MUC5AC Mucin Gene Expression and Production from Cultured Airway Epithelial Cells

et al. 2014

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BackgroundWe investigated whether wogonin and apigenin significantly affect the epidermal growth factor receptor (EGFR) signaling pathway involved in MUC5AC mucin gene expression, and production from cultured airway epithelial cells; this was based on our previous report that apigenin and wogonin suppressed MUC5AC mucin gene expression and production from human airway epithelial cells.MethodsConfluent NCI-H292 cells were pretreated with wogonin or apigenin for 15 minutes or 24 hours and then stimulated with epidermal growth factor (EGF) for 24 hours or the indicated periods.ResultsWe found that incubation of NCI-H292 cells with wogonin or apigenin inhibited the phosphorylation of EGFR. The downstream signals of EGFR such as phosphorylation of MEK1/2 and ERK1/2 were also inhibited by wogonin or apigenin.ConclusionThe results suggest that wogonin and apigenin inhibits EGFR signaling pathway, which may explain how they inhibit MUC5AC mucin gene expression and production induced by EGF.

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Section: Introductionmentioning

confidence: 85%

Apigenin and Wogonin Regulate Epidermal Growth Factor Receptor Signaling Pathway Involved in MUC5AC Mucin Gene Expression and Production from Cultured Airway Epithelial Cells

et al. 2014

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“…This has led to efforts in the identification of new compounds that inhibit mucus production and gene expression. It was previously found that glycyrrhizin, derived from G. uralensis, inhibits MUC5AC gene expression (Lee et al, 2011). However, the present study found that 7,4′-DHF was 28 times more potent in inhibiting MUC5AC secretion than glycyrrhizin with IC 50 values of 1.4 and 38 μM, respectively, without detectable cytotoxicity; 10-μM 7,4′-DHF also significantly inhibited PMA-stimulated MUC5AC gene expression, whereas a tenfold higher concentration of glycyrrhizin (100 μM) was required (Lee et al, 2011).…”

Section: The Flavonoid 74′-dihydroxyflavone Inhibits Muc5acmentioning

confidence: 99%

“…It was previously found that glycyrrhizin, derived from G. uralensis, inhibits MUC5AC gene expression (Lee et al, 2011). However, the present study found that 7,4′-DHF was 28 times more potent in inhibiting MUC5AC secretion than glycyrrhizin with IC 50 values of 1.4 and 38 μM, respectively, without detectable cytotoxicity; 10-μM 7,4′-DHF also significantly inhibited PMA-stimulated MUC5AC gene expression, whereas a tenfold higher concentration of glycyrrhizin (100 μM) was required (Lee et al, 2011). Flavonoids are widely distributed secondary metabolites and currently consumed in large amounts in the daily diet with antiinflammatory, antilipidemic, antihyperglycemic, antiviral, hepatoprotective, gastric antiulcer, cardioprotective, neuroprotective, antioxidant, and anticancer actions (Romano et al, 2013).…”

Section: The Flavonoid 74′-dihydroxyflavone Inhibits Muc5acmentioning

confidence: 99%

The Flavonoid 7,4′‐Dihydroxyflavone Inhibits MUC5AC Gene Expression, Production, and Secretion via Regulation of NF‐κB, STAT6, and HDAC2

Liu

Weir

Busse

et al. 2015

Phytotherapy Research

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Mucus overproduction is a significant component of the pathophysiology of obstructive lung diseases. Currently, there are only a few medications available that inhibit mucus production. Previous studies showed that glycyrrhizin, a triterpenoid in Glycyrrhiza uralensis (G. uralensis) inhibits mucin 5AC (MUC5AC) mRNA and protein expression. Other potential mucus production inhibitory compounds contained within in G. uralensis have not been fully investigated. The aim of the present study was to determine if the G. uralensis flavonoid 7,4'-dihydroxyflavone (7,4'-DHF), inhibits MUC5AC gene expression, mucus production and secretion and if so, to elucidate the mechanism of this inhibition. 7,4'-DHF significantly decreased phorbol 12-myristate 13-acetate (PMA) stimulated NCI-H292 human airway epithelial cell MUC5AC gene expression and mucus production, at a 28 fold lower concentration than glycyrrhizin (IC50 value of 1.4µM vs 38 µM, respectively), 7,4'-DHF also inhibited MUC5AC mucus secretion. Inhibition was associated with the suppression of NF-κB, STAT6 activation and enhanced HDAC2 expression. In a murine model of asthma, 7,4'-DHF treated mice exhibited a marked reduction in MUC5AC secretion in the bronchoalveolar lavage (BAL) fluid compared with control mice. These findings, together with previous findings linking NF-κB, STAT6 and HDAC2 modulation to the control of MUC5AC expression, demonstrate that 7,4'-DHF is a newly identified component of G. uralensis that regulates MUC5AC expression and secretion via regulation of NF-κB, STAT6 and HDAC2.

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“…We have tried to investigate the possible activities of some natural products on mucin production (secretion) from airway epithelial cells. As a result of our trial, we previously reported that several natural compounds affected mucin production and/or secretion from airway epithelial cells (Heo et al ., ; Lee et al ., ; Lee et al ., ; Lee et al ., ). According to folk medicine and a number of reports, Scutellariae Radix has been used to control airway allergic or inflammatory diseases, and one of its components, wogonin, was reported to have diverse biological activities including antioxidative, anti‐inflammatory and anticancer effects (Paoletti et al ., ; Zhong et al ., ; Clere et al ., ; Zhou et al ., ; McVean et al ., ; Yin et al ., ; Illek and Fischer, ).…”

Section: Introductionmentioning

confidence: 98%

Inhibition of TNF‐α‐Induced MUC5AC Mucin Gene Expression and Production by Wogonin Through the Inactivation of NF‐κB Signaling in Airway Epithelial Cells

Sikder

Lee

Mia

et al. 2013

Phytotherapy Research

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In this study, we investigated whether wogonin significantly affects MUC5AC mucin gene expression and production in human airway epithelial cells. Confluent NCI-H292 cells were pretreated with wogonin for 30 min and then stimulated with tumor necrosis factor-α (TNF-α) for 24 h or the indicated periods. The MUC5AC mucin gene expression and mucin protein production were measured by RT-PCR and ELISA, respectively. We found that incubation of NCI-H292 cells with wogonin significantly inhibited mucin production and down-regulated MUC5AC gene expression induced by TNF-α in a dose-dependent fashion. To elucidate the action mechanism of wogonin, effect of wogonin on TNF-α-induced NF-κB signaling pathway was investigated by western blot analysis. Wogonin inhibited NF-κB activation induced by TNF-α. Inhibition of IKK by wogonin led to the suppression of IκB phosphorylation and degradation, p65 nuclear translocation and NF-κB-regulated gene expression. This, in turn, led to the down-regulation of MUC5AC protein production in NCI-H292 cells. Wogonin also inhibited the gene products involved in cell survival (Bcl-2) and proliferation (cyclooxygenase-2). These results suggest that wogonin inhibits the NF-κB signaling pathway, which may explain its role in the inhibition of MUC5AC mucin gene expression and production.

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Inhibition of airway MUC5AC mucin production and gene expression induced by epidermal growth factor or phorbol ester by glycyrrhizin and carbenoxolone

Cited by 13 publications

References 19 publications

Apigenin and Wogonin Regulate Epidermal Growth Factor Receptor Signaling Pathway Involved in MUC5AC Mucin Gene Expression and Production from Cultured Airway Epithelial Cells

Apigenin and Wogonin Regulate Epidermal Growth Factor Receptor Signaling Pathway Involved in MUC5AC Mucin Gene Expression and Production from Cultured Airway Epithelial Cells

The Flavonoid 7,4′‐Dihydroxyflavone Inhibits MUC5AC Gene Expression, Production, and Secretion via Regulation of NF‐κB, STAT6, and HDAC2

Inhibition of TNF‐α‐Induced MUC5AC Mucin Gene Expression and Production by Wogonin Through the Inactivation of NF‐κB Signaling in Airway Epithelial Cells

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