• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.114.2-114.2
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• 2000

• 대한한방소아과학회지
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• 제30권2호
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• pp.31-46
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• 2016

Objectives In this study, the effects of Ja-eum-gang-hwa-tang (JGT) on the increase in airway epithelial mucosubstances of rats and ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells were investigated. Materials and Methods Hypersecretion of airway mucus was produced by exposure of $SO_2$ to rats for 3 weeks. The effect of orally-administered JGT for 2 weeks on increased epithelial mucosubstances from tracheal goblet cells of rats was assessed by using histopathological analysis after staining the epithelial tissue with Hematoxylin-eosin and PAS-alcian blue. Possible cytotoxicity of JGT was assessed by investigating the potential damage on kidneys and liver functions by measuring serum GOT/GPT activities and serum BUN concentration of rats and the body weight gain during experiment. Also, the effect of JGT on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of JGT and treated with ATP ($200{\mu}M$) or PMA ($10ng/ml$) or EGF ($25ng/ml$) or TNF-${\alpha}$ (0.2 nM) for 24 hrs to assess the effect of JGT both on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production by using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). Results (1) JGT decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) JGT did not show any renal and hepatic toxicities, and did not affect body weights either. (3) JGT significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions from NCI-H292 cells. (4) JGT inhibited EGF-, and PMA-induced expression levels of MUC5AC gene in NCI-H292 cells. However, ATP- and TNF-${\alpha}$-induced MUC5AC gene expression levels were not affected in NCI-H292 cells. Conclusions The result from the present study suggests that JGT might control the production and gene expression of airway mucin observed in various respiratory diseases which accompanied by mucus hypersecretion. Also, JGT did not show liver toxicity or impact on kidney functions. The effect of JGT should be further studied by using animal experimental models which can show proper pathophysiology of airway diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제10권5호
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• pp.251-254
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• 2006

Schizandrae Fructus has been used for controlling respiratory allergic or inflammatory diseases in folk medicine and their components, schizandrin, schizandrin-A and gomisin-A were reported to have diverse biological effects. In this study, we investigated whether schizandrin, schizandrin-A and gomisin-A affect adenosine triphosphate (ATP)-induced mucin secretion from cultured airway epithelial cells. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radio labeled using $^{3}H-glucosamine$ for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on $^{3}H-mucin$ secretion. The results were as follows: 1) schizandrin significantly inhibited ATP-induced mucin secretion; 2) However, schizandrin-A and gomisin-A did not affect ATP-induced mucin secretion, significantly. We conclude that schizandrin can inhibit ATP-induced mucin secretion by directly acting on airway mucin-secreting cells. Therefore, schizandrin should further be investigated for the possible use as mucoregulators in the treatment of inflammatory airway diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제10권6호
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• pp.317-321
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• 2006

In this study, we investigated whether glycyrrhizin, prunetin and morroniside affect mucin secretion from cultured airway epithelial cells and compared the possible activities of these agents with the inhibitory action on mucin secretion by poly-L-lysine (PLL) and the stimulatory action by adenosine triphosphate (ATP). Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled using $^{3}H-glucosamine$ for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on $^{3}H-mucin$ secretion. The results were as follows: 1) glycyrrhizin and morroniside increased basal mucin secretion from airway; 2) prunetin did not affect basal mucin secretion; 3) glycyrrhizin did not inhibit ATP-induced mucin secretion. We conclude that glycyrrhizin and morroniside can increase basal mucin secretion, by directly acting on airway mucin-secreting cells and suggest that two compounds be further investigated for the possible use as mild expectorants during the treatment of inflammatory airway diseases.

• Biomolecules & Therapeutics
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• 제14권4호
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• pp.202-206
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• 2006

Angelicae Dahiricae Radix has been used for controlling inflammatory respiratory diseases in oriental medicine and their components, phellopterin, isoimperatorin and byakangelicol were reported to have various biological effects. In this study, we investigated whether phellopterin, isoimperatorin and byakangelicol affect adenosine triphosphate(ATP)-induced mucin secretion from cultured airway epithelial cells. Confluent primary hamster tracheal surface epithelial(HTSE) cells were metabolically radiolabeled using $^3H$-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on $^3H$-mucin secretion. The results were as follows: 1) phellopterin significantly inhibited ATP-induced mucin secretion; 2) However, isoimperatorin and byakangelicol did not affect ATP-induced mucin secretion, significantly. This result suggests that phellopterin can regulate 'mucin secretion induced by ATP'-a phenomenon simulating mucus overproduction from inflamed airway epithelial cells-by directly acting on airway mucin-secreting cells. Therefore, phellopterin should further be investigated for the possible use as mucoregulators in the treatment of inflammatory airway diseases.

• Biomolecules & Therapeutics
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• 제14권4호
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• pp.235-239
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• 2006

Angelicae Koreanae Radix has been used for controlling inflammatory respiratory diseases in folk medicine and their components, imperatorin, marmesinin and oxypeucedanin were reported to have diverse biological effects. In this study, we investigated whether imperatorin, marmesinin and oxypeucedanin affect adenosine triphosphate(ATP)-induced mucin secretion from cultured airway epithelial cells. Confluent primary hamster tracheal surface epithelial(HTSE) cells were metabolically radiolabeled using $^3H$-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on $^3H$-mucin secretion. The results were as follows: 1) imperatorin significantly inhibited ATP-induced mucin secretion; 2) However, marmesinin and oxypeucedanin did not affect ATP-induced mucin secretion, significantly. We conclude that imperatorin might inhibit ATP-induced mucin secretion by directly acting on airway mucin-secreting cells. Therefore, imperatorin should further be investigated for the possible use as mucoregulators in the treatment of inflammatory airway diseases.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.94-94
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• 1997

The objective of this study was to generate and characterize monoclonal antibodies against rat airway mucins, and therefore, should serve as a useful tool in studying the regulation of airway mucins using various in vivo rat models that are currently available. As an antigen, we used a high molecular mass mucin preparation purified from the spent media of rat tracheal surface epithelial cells in primary culture. Seven hybridomas were obtained which secrete monoclonal antibodies against the rat mucin among which mAbRT03 showed the highest immunoreactivity against the mucin based on ELISA. All of the antibodies secreted by these hybridomas recognized carbohydrate epitopes but not sialic acid residues since their immunoreactivity was completely abolished by treatment of the mucin with 20 mM periodate but not with neuraminidase. Further characterization of mAbRT03 showed that: (1) it belongs to the IgM type, (2) it binds to high molecular mass mucins based on both Western blot analysis and indirect immunoprecipitation, (3) it binds to the luminal side of tracheal epithelium as well as some goblet cells based on immunohistochemistry, and (4) it also recognizes in vive airway mucins from rats but not from human nor hamsters which have been purified from the airway lavage fluids. This is the first anti-rat airway mucin monoclonal antibody which has been developed against purified rat airway mucins. Therefore, mAbRT03 should be able to serve as an invaluable tool in studying the regulation of airway mucins using various intact rat models that are currently available.

• Biomolecules & Therapeutics
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• 제9권4호
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• pp.263-269
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• 2001

In this study, we tried to investigate whether poly-L-arginine (PLA) (MW 10,800) significantly affect mucin release from cultured hamster airway goblet cells and the mucosubstances of hypersecretory air-way goblet cells of rats. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with $^3$H-glucosamine for 24 hr and chased for 30 min in the presence of varying concentrations of PLA to assess the effects on $^3$H-mucin release. Possible cytotoxicities of PLA were assessed by measuring both Lactate Dehydrogenate (LDH) release and by checking the possible changes on the morphology of HTSE cells during treatment. For in vivo experiment, hyperplasia of rat airway goblet cells and increase in intraepithelial mucosubstances were induced by exposing rats to SO$_2$ for 3 weeks and varying concentrations of PLA were administered inhalationally to assess the effects on the mucosubstances of airway goblet cells of rats. The results were as follows : (1) PLA significantly inhibited mucin release from cultured HTSE cells in a dose-dependent manner; (2) there was no significant release of LDH and no significant change on the morphology of cultured HTSE cells during treatment; (3) PLA also affected the intraepithelial mucosubstances of hypersecretory rats and restored them to the levels of control animals. We conclude that PLA inhibit mucin release from airway goblet cells without significant cytotoxicity and possibly normalize the hypersecretion of airway mucosubstances in vivo. This finding suggests that PLA might function as an airway mucoregulative agent.

• 대한한의학회지
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• 제29권3호
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• pp.76-87
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• 2008

Objectives: In this study, the author investigated whether Haengso-tang (HST) and Chwiyeon-tang (CHT) affect both in vitro mucin secretion and MUC5AC gene expression in airway epithelial cells and in vivo mucin secretion from animal model for airway mucus hypersecretion. Materials and Methods: Confluent HTSE cells (non-labeled) were chased for 30 min in the presence of HST and CHT to assess the effects of the agents on mucin secretion by enzyme-linked immunosorbent assay (ELISA), with removal of oriental herbal medicine extract from each agent-treated sample by centrifuge microfilter. Also, the effects of the agents on TNF- or EGF-induced MUC5AC gene expression in human airway epithelial cells (NCI-H292) were investigated. The author also induced hypersecretion of airway mucus by exposure of rats to SO2 for 3 weeks. Effects of orally-administered HST and CHT during 1 week on in vivo mucin secretion from tracheal goblet cells of rats were assessed using ELISA. Results: (1) HST significantly decreased in vitro mucin secretion from cultured HTSE cells. However, CHT did not affect in vitro mucin secretion from HTSE cells; (2) CHT significantly inhibited the expression levels of EGF- or TNF-alpha-induced MUC5AC gene in NCI-H292 cells. However, HST did not affect the expression levels of EGF- or TNF-alpha-induced MUC5AC gene in NCI-H292 cells; (3) CHT significantly inhibited hypersecretion of in vivo mucin. However, HST did not affect hypersecretion of in vivo mucin. Conclusion: These results suggest that CHT can not only affect the secretion of mucin but also the expression of the mucin gene and could be helpful for treating pulmonary disease caused by secretion of mucin.

• 대한한방소아과학회지
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• 제29권3호
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• pp.65-79
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• 2015

Objectives : In this study, effects of haepyoijintang (HIJ) on the increase in airway epithelial mucosubstances of rats and ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells were investigated. Methods : Hypersecretion of airway mucus was induced by exposure of rats to $SO_2$ during 3 weeks. Effect of orally-administered HIJ during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was evaluated using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of HIJ was evaluated by examining the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN and creatinine concentrations of rats and the body weight gain during experiment, after administering HIJ orally. At the same time, the effect of HIJ on ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of HIJ and treated with ATP ($200{\mu}M$), PMA (10 ng/ml), EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24 hrs, to evaluate the effect of HIJ both on ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). Results : (1) HIJ decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) HIJ did not show renal and hepatic toxicities and did not affect body weight gain of rats during experiment. (3) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions from NCI-H292 cells. (4) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin gene expression from NCI-H292 cells. Conclusions : The result from the present study suggests that HIJ might control the production and gene expression of airway mucin observed in various respiratory diseases accompanied by mucus hypersecretion and do not show in vivo toxicity to liver and kidney functions after oral administration. Effect of HIJ with their diverse components should be further investigated using animal experimental models that can reflect the pathophysiology of airway diseases through future studies.