• Natural Product Sciences
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• v.22 no.4
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• pp.275-281
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• 2016

Perilla frutescens was empirically used for controlling airway inflammatory diseases in folk medicine. We investigated whether caffeic acid, myristicin and rosemarinic acid derived from Perilla frutescens significantly affect the gene expression and production of mucin from airway epithelial cells. Confluent NCI-H292 cells were pretreated with caffeic acid, myristicin or rosemarinic acid for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. The MUC5AC mucin gene expression and production were measured by reverse transcription - polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Additionally, we examined whether caffeic acid, myristicin or rosemarinic acid affects MUC5AC mucin production indued by epidermal growth factor (EGF) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), the other two stimulators of production of airway mucin. The results were as follows: (1) Caffeic acid, myristicin and rosemarinic acid inhibited the gene expression and production of MUC5AC mucin induced by PMA from NCI-H292 cells, respectively; (2) Among the three compounds derived from Perilla frutescens, only rosemarinic acid inhibited the production of MUC5AC mucin induced by EGF or $TNF-{\alpha}$, the other two stimulators of production of airway mucin. These results suggest that rosemarinic acid derived from Perilla frutescens can regulate the production and gene expression of mucin, by directly acting on airway epithelial cells and, at least in part, explains the traditional use of Perilla frutescens as remedies for diverse inflammatory pulmonary diseases.

• Korean Journal of Oriental Medicine
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• v.2 no.1
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• pp.314-326
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• 1996

Experimental studies were done to research the clinical effect of Insamyunpye-H wan on viscousity of mucin solution, pulmonary thromboembolism, oxygen consumption in $O_3$-exposed and Lung TBA in rats and mice. The result was obtained as follows : 1. In the effect of viscosity sampled from mucin, Insamyunpye-Hwan was revealed to have a significant effect of decrease in the rate of viscousity (p<0.01). 2. In the effect of sodium aracdonic acid induced pulmonary thromboembolism, I samyunpye-Hwan was revealed to have an effect of increasing the number of survival, but were not significant 3. In the effect of ADP induced pulmonary thrornboembolism, Insamyunpye-Hw an was revealed to have an effect of increasing the number of survival, but were not significant 4. In the effect of oxygen cansumption values in rats exposed-$O_3$, Insarnyunpye-Hwan was revealed to have a significant effect (p<0.05). 5. In the effect of the lung TBA values in rats exposed-$O_3$, Isamyunpye-Hwan was revealed to have a significant effect (p<0.05). In connection with the results of the studies, Insamyunpye-Hwan is concluded to be effective on the treatment of cough and lung and respiratory organ damages.

• Tuberculosis and Respiratory Diseases
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• v.78 no.3
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• pp.210-217
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• 2015

Background: Adenophora triphylla var. japonica is empirically used for controlling airway inflammatory diseases in folk medicine. We evaluated the gene expression and production of mucin from airway epithelial cells in response to lupenone, lupeol and taraxerol derived from Adenophora triphylla var. japonica. Methods: Confluent NCI-H292 cells were pretreated with lupenone, lupeol or taraxerol for 30 minutes and then stimulated with tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) for 24 hours. The MUC5AC mucin gene expression and production were measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Additionally, we examined whether lupenone, lupeol or taraxerol affects MUC5AC mucin production induced by epidermal growth factor (EGF) and phorbol 12-myristate 13-acetate (PMA), the other 2 stimulators of airway mucin production. Results: Lupenone, lupeol, and taraxerol inhibited the gene expression and production of MUC5AC mucin induced by TNF-${\alpha}$ from NCI-H292 cells, respectively. The 3 compounds inhibited the EGF or PMA-induced production of MUC5AC mucin in NCI-H292 cells. Conclusion: These results indicated that lupenone, lupeol and taraxerol derived from Adenophora triphylla var. japonica regulates the production and gene expression of mucin, by directly acting on airway epithelial cells. In addition, the results partly explain the mechanism of of Adenophora triphylla var. japonica as a traditional remedy for diverse inflammatory pulmonary diseases.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.303-310
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• 2021

In the present study, kaempferol, a flavonoidal natural compound found in Polygonati Rhizoma, was investigated for its potential effect on the gene expression and production of airway MUC5AC mucin. A human respiratory epithelial NCI-H292 cells was pretreated with kaempferol for 30 min and stimulated with epidermal growth factor (EGF) or phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect on PMA-induced nuclear factor kappa B (NF-κB) signaling pathway or EGF-induced mitogen-activated protein kinase (MAPK) signaling pathway was investigated. Kaempferol suppressed the production and gene expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IκBα), and NF-κB p65 nuclear translocation. Also, kaempferol inhibited EGF-induced gene expression and production of MUC5AC mucin through regulating the phosphorylation of EGFR, phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These results suggest kaempferol regulates the gene expression and production of mucin through regulation of NF-κB and MAPK signaling pathways, in human airway epithelial cells.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.431-436
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• 2020

In this study, diclofenac, a non-steroidal anti-inflammatory drug, was investigated for its potential effect on the gene expression and production of airway MUC5AC mucin. The human respiratory epithelial NCI-H292 cells were pretreated with diclofenac for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of diclofenac on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated. Diclofenac suppressed the production and gene expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest diclofenac regulates the gene expression and production of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

• The Journal of Pediatrics of Korean Medicine
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• v.31 no.2
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• pp.1-13
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• 2017

Objectives In this study, the author intended to investigate whether Gami-cheongpetang (GCP), Gagam-jeongkitang (GJG), Gami-samooltang (GSM) and Gami-ijoongtang (GIJ) significantly affect in vivo (animal model) and in vitro (cultured cells) mucin secretion and MUC5AC gene expression in airway epithelial cells. Methods For in vivo experiment, the author induced hypersecretion of airway mucin in rats by introducing SO2 for 3 weeks. Enzyme-linked immunosorbent assay (ELISA) was used to assess the effects of orally-administered GCP, GJG, GSM and GIJ in vivo mucin secretion from tracheal goblet cells of rats after 1 week. Also, the effects of the agents on TNF- or EGF-induced MUC5AC gene expression in human airway epithelial cells (NCI-H292) were investigated. Possible cytotoxicities of the agents were assessed by examining the rate of survival and proliferation of NCI-H292 cells. Results (1) GCP and GJG significantly inhibited hypersecretion of in vivo mucin, although GSM and GIJ did not affect hypersecretion of in vivo mucin; (2) GCP and GJG significantly increased in vitro mucin secretion from cultured HTSE cells. However, GSM and GIJ did not affect in vitro mucin secretion from HTSE cells; (3) GCP and GJG significantly inhibited the expression levels of EGF-induced MUC5AC gene in NCI-H292 cells. However, GSM and GIJ increased the expression levels of EGF-induced MUC 5AC gene in NCI-H292 cells; (4) GCP, GJG, GSM and GIJ did not significantly inhibit the survival and proliferation of NCI-H292 cells. Conclusions These results suggest that GCP, GJG, GSM and GIJ can not only affect the secretion of mucin but also affect the expression of mucin gene. The author suggests that the effects of GCP, GJG, GSM and GIJ with their components should be further investigated by using animal experimental models that simulate the diverse pathophysiology of pulmonary diseases.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.293-301
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• 2020

Hypersecretion of pulmonary mucus is a major pathophysiological feature in allergic and inflammatory respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD). Overproduction and/or oversecretion of mucus cause the airway obstruction and the colonization of pathogenic microbes. Developing a novel pharmacological agent to regulate the production and/or secretion of pulmonary mucus can be a useful strategy for the effective management of pathologic hypersecretion of mucus observed in COPD and asthma. Thus, in the present review, we tried to give an overview of the conventional pharmacotherapy for mucus-hypersecretory diseases and recent research results on searching for the novel candidate agents for controlling of pulmonary mucus hypersecretion, aiming to shed light on the potential efficacious pharmacotherapy of mucus-hypersecretory diseases.

• Tuberculosis and Respiratory Diseases
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• v.57 no.6
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• pp.594-598
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• 2004

Signet ring cell carcinoma of lung is an unique variant of mucin producing adenocarcinoma which is characterized by abundant intracellular mucin accumulation. Only a few cases of primary signet ring cell carcinoma of lung have been reported in the world wide literature. And we have, recently experienced one case of primary signet ring cell carcinoma of lung. A 55 years old man was evaluated for paralysis of lower extremities and was found to have lung cancer in the left upper and lower lobe with pleural, multiple spinal, bone and liver metastases. Signet ring tumor cells were revealed by cytologic examination of pleural fluids. And there were no evidence of signet ring cell carcinoma of other organs. Primary signet ring cell carcinoma of lung seems to have an aggressive behavior and therapeutic modalities could be different from those for signet ring cell carcinomas from other organs. Therefore it is important to separate primary signet ring cell adenocarcinoma of lung from metastatic tumors.

• The Journal of Pediatrics of Korean Medicine
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• v.21 no.2
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• pp.69-88
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• 2007

Objectives In this study, we investigated the clinical effect of Imoyongsutang and Imoyongsutang plus Maduryong on the viscosity of mucin solution, the instantly type allergy, the delayed type allergy, the carbon clearance, the pulmonary thromboembolism for the lung damaged rats and mice. Methods The gastric mucin and incubation time, pulmonary thromboembolism induced by sodium arachidonic acid, the pulmonary thromboembolism induced by ADP, vascular permeability response, non inhibitory effects, the delayed type hypersensitivity response to picryl chloride, serum $Na^+$ level, $K^+$ and $Cl^-$ level, ${\alpha}-index$ in phagocytic activity were measured. Results 1. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong gave some high significance results on the gastric mucin and incubation time on the viscosity of mucin solution in rats, and both groups had similar result. 2. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were revealed feeble effect on the pulmonary thromboembolism induced by sodium arachidonic acid in mice, and both groups had similar result. 3. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were revealed feeble effect on the pulmonary thromboembolism induced by ADP in mice, and after medication, the value was increased than the before one. 4. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were recognized. significance on vascular permeability response induced by histamine in rats. And the significance of the Imoyongsutang plus Maduryong is rather higher than that of Imoyongsutang. 5. The extract of Imoyongsutang recognized no significance symptoms on vascular permeability response induced by serotonin in rats, but the solid extract of Imoyongsutang plus Maduryong resulted recognized significance. 6. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were revealed non inhibitory effects on the 48 hour homologous PCA in rats provoked by the IgE-like antibody against the egg albumin. 7. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were remarkably revealed inhibitory effect on the delayed type hypersensitivity response to picryl chloride in mice. And the significance of the latter is rather higher than that of the former. 8. The solid extract of Imoyongsutang was revealed inhibitory eects on the delayed type hypersensitivity response to SRBC in mice, but thffe solid extract of Imoyongsutang plus Maduryong recognized significance. 9. The solid extract of Imoyongsutang was recognized significance on the lung TBA value of $O_3$ intoxicated rats, but the solid extract of Imoyongsutang plus Maduryong recognized no significance. 10. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong was recognized significance on serum $Na^+$ level in $O_{3}-intoxicated$ rats. And the significance of the latter is rather higher than that of the former. 11. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were revealed non inhibitory effects on serum $K^+$ and $CL^-$ level $O_{3}-intoxicated$ Rats 12. The solid extracts Imoyongsutang was recognized significance on K-index in phagocytic activity in mice, but the solid extract of Imoymgsutang plus Maduryong recognized no significance. 13. The solid extract Imoyongsutang was recognized on significance on ${\alpha}-index$ in phagocytic activity in mice. but the solid extract of Imoyongsutang plus Maduryong recognized significance. Conclusions According to the above findings, it is suggested that the sold extract of Imoyongsutang and Imoyongsutang plus Maduryong were revealed effects on asthma cough or dyspnea caused by the abnormal rising of lung-allergy and throat discomfort so that they retain effectiveness on the instantly and delayed type allergy, the pulmonary thromboembolism and the lung damages in rats and mice.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.770-780
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• 2002

The airway surface liquid (ASL), often referred to as mucus, is a thin layer of fluid covering the luminal surface of the airway. The major function of mucus is to protect the lung through mucociliary clearance against foreign particles and chemicals entering the lung. The mucus is comprised of water, ions, and various kinds of macromolecules some of which possess the protective functions such as anti-microbial, anti-protease, and anti-oxidant activity. Mucus glycoproteins or mucins are mainly responsible for the viscoelastic property of mucus, which is crucial for the effective mucociliary clearance. There are at least eight mucin genes identified in the human airways, which will potentially generate various kinds of mucin molecules. At present, neither the exact structures of mucin proteins nor their regulation are understood although it seems likely that different types of mucins are involved in different functions and might also be associated with certain airway diseases. The fact that mucins are tightly associated with various macromolecules present in ASL seems to suggest that the defensive role of ASL is determined not only by these individual components but rather by a combination of these components. Collectively, mucins in ASL may be compared to aircraft carriers carrying various types of weapons in defense of airborne enemies.