Expectorant and antitussive effect of Hedera helix and Rhizoma coptidis extracts mixture

PURPOSE: This study aims to investigate the additive effect of the Hedera helix (HH) and Rhizoma coptidis (RC) extracts mixture on antitussive and expectorant activities in animals. MATERIALS AND METHODS: The expectorant assay was performed with phenol red secretion in mice trachea. Mice or guinea pigs were randomly divided into groups of 8 each, including negative and positive control groups. After gastric administration of the test extracts in mice, 2.5% phenol red solution (0.2 mL) was intraperitoneally injected. Trachea was dissected and optical density of tracheal secretion was measured. After gastric administration of the test extracts in guinea pigs, the antitussive activities were assessed using a citric acid-induced cough measurement. RESULTS: The extracts of HH and RC significantly increased tracheal secretion and inhibited cough. The mixture of HH and RC extracts in a 1:1 concentration at a dose of 200 mg/kg showed a more potent effect on phenol red secretion (25.25±3.14) and cough inhibition (61.25±5.36) than the individual use of each extracts [phenol red secretion; HH 13.39±4.22 (p=0.000), RC 20.78±2.50 (p=0.010), cough inhibition; HH 9.89±4.14 (p=0.010), RC 30.25±7.69 (p=0.000)]. A 3:1 ratio mixture of HH to RC demonstrated an optimal expectorant effect (p<0.001), and this mixture showed expectorant and antitussive effects in a dose-dependent manner. CONCLUSION: This study provides evidence for antitussive and expectorant effect of a 3:1 mixture of HH and RC, which may be a useful therapeutic option for respiratory diseases.ope

Cholesterol Depletion in Cell Membranes of Human Airway Epithelial Cells Suppresses MUC5AC Gene Expression

PURPOSE: If cholesterol in the cell membrane is depleted by treating cells with methyl-β-cyclodextrin (MβCD), the activities of transmembrane receptors are altered in a cell-specific and/or receptor-specific manner. The proinflammatory cytokines, IL-1β is potent inducers of MUC5AC mRNA and protein synthesis in human airway epithelial cells. Cells activated by IL-1β showed increased phosphorylation of extracellular signal regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). Thus, we investigated the effects of cholesterol depletion on the expression of MUC5AC in human airway epithelial cells and whether these alterations to MUC5AC expression were related to MAPK activity. MATERIALS AND METHODS: After NCI-H292 cells were pretreated with 1% MβCD before adding IL-1β for 24 hours, MUC5AC mRNA expression was determined by reverse transcription- polymerase chain reaction (RT-PCR) and real time-PCR. Cholesterol depletion by MβCD was measured by modified microenzymatic fluorescence assay and filipin staining. The phosphorylation of IL-1 receptor, ERK and p38 MAPK, was analyzed by western blot. RESULTS: Cholesterol in the cell membrane was significantly depleted by treatment with MβCD on cells. IL-1β-induced MUC5AC mRNA expression was decreased by MβCD and this decrease occurred IL-1-receptor- specifically. Moreover, we have shown that MβCD suppressed the activation of ERK1/2 and p38 MAPK in cells activated with IL-1β. This result suggests that MβCD-mediated suppression of IL-1β-induced MUC5AC mRNA operated via the ERK- and p38 MAPK-dependent pathway. CONCLUSION: Cholesterol depletion in NCI-H292 cell membrane may be considered an anti-hypersecretory method since it effectively inhibits mucus secretion of respiratory epithelial cells.ope

Effects of dietary polyphenols on expression of MUC5AC gene in respiratory epithelial cell

의학과/석사[한글]식이 폴리페놀(Polyphenol)이란 우리가 섭취하는 음식 특히 식물에 포함되어 있는 폴리페놀을 일컫는데 최근 먹거리에 대한 관심이 높아지면서 이에 대한 연구가 활발하다. 이들은 항염증 (anti-inflammatory), 항산화(anti-oxidative), 항돌연변이(anti-mutagenic), 항암, 세포고사 유도 등의 작용을 하지만 폴리페놀이 코점막에서 발생하는 점액과분비나 섬모운동에 어떤 영향을 미치는가에 대해서는 연구가 미미한 실정이다. 이에 본 연구의 목적으로 첫째, 사람 호흡기 상피세포인 NCI-H292 세포에 여러 식이 폴리페놀([6]-gingerol, EGCG, curcumin, quercetin)을 처치하여 폴리페놀이 MUC5AC 유전자 발현을 억제하는 가를 알아보고자 하였다. 다음으로 세포의 증식을 억제하지 않고 MUC5AC 유전자 발현을 억제하는 농도로 폴리페놀을 사람 코점막에 처치하여 폴리페놀이 섬모운동에 미치는 영향을 보고자 하였다. NCI-H292 세포주에 4종의 폴리페놀([6]-gingerol, EGCG, curcumin, quercetin)을 각각 투여하였다. 이들이 MUC5AC 유전자 발현을 억제하는 최소농도를 real-time PCR법으로 알아본 결과, [6]-gingerol은 1 μM, EGCG 20 μM, quercetin 40 μM, curcumin은 10 μM이었으며, 실험한 폴리페놀들은 이 농도에서 세포증식을 억제하지 않았다. 정상 사람 코점막에서의 섬모운동 변화는 [6]-gingerol, quercetin, EGCG의 경우 대조군과 유의한 차이를 보이지 않았으나 curcumin에서는 유의하게 감소하는 것을 확인할 수 있었다. 결론적으로 [6]-gingerol, quercetin, EGCG 등은 호흡기 상피세포의 점액분비를 효과적으로 억제하며 코점막 섬모운동은 정상적으로 유지하므로 임상적으로 이용 가능한 점액분비 억제물질로 생각된다. [영문]1. Background and objective Dietary polyphenols have been widely consumed in food, and their anti-inflammatory, anti-oxidative and anti-mutagenic activities have been recently studied. However, the effect on mucin hypersecretion or mucociliary movement of dietary polyphenol has not been elucidated yet. Therefore, this study was to investigate whether dietary polyphenols ([6]-gingerol, EGCG, curcumin, quercetin) inhibit MUC5AC gene expression, and if so, whether they would have effect on the ciliary movement of human nasal mucosa. 2. Material and method After NCI-H292 cells had been treated with IL-1β (10 ng/ml) and pretreated with 4 different dietary polyphenols ([6]-gingerol, EGCG, curcumin, quercetin), the mRNA expression of MUC5AC was determined by real-time polymerase chain reaction. Normal nasal mucosa was obtained during sphenoid sinusotomy and treated with minimal inhibitory concentration of each polyphenol. Ciliary movement was assessed via inverted microscope and computerized program. 3. Result Minimal inhibitory concentration of MUC5AC gene expression in each polyphenol was found as following; [6]-gingerol 1 μM, EGCG 20 μM, quercetin 40 μM, and curcumin 10 μM. Each polyphenol did not influence cell proliferation at this minimal inhibitory concentration. In assessment of ciliary movement, [6]-gingerol, quercetin, EGCG did not show any difference between control group and experiment group, but curcumin showed decrease of ciliary movement. 4. Conclusion [6]-gingerol, quercetin, and EGCG suppress MUC5AC gene expression and maintain normal ciliary movements. Therefore, these polyphenols may be used as anti-hypersecretory agents and the further clinical study will be needed.ope

Anti-adhesive effect of a thermosensitive poloxamer applied after the removal of nasal packing in endoscopic sinus surgery: a randomised multicentre clinical trial

OBJECTIVE: To compare the efficacies of a thermosensitive poloxamer (TPX) and Merogel in preventing adhesion applied after the removal of nasal packing in endoscopic sinus surgery as a non-inferiority trial. DESIGN: Randomised, multicentre, single-blind, active-controlled, matched-pair study. SETTING: Yonsei University Gangnam Severance Hospital, Korea University Guro Hospital. PARTICIPANTS: A total of 70 patients were enroled and underwent endoscopic sinus surgeries. Four of the patients did not complete their follow-up. Analysis of the 66 enroled patients having completed postoperative assessment was performed. The severity of rhinosinusitis was graded with a Lund-McKay CT score, and only those with bilateral disease and a CT score difference ≤2 between sinuses were included. MAIN OUTCOME MEASURES: An independent rhinologist from a third institution through a blinded assessment with digital photoendoscopy of the middle meati bilaterally taken postoperatively. RESULTS: In the blinded assessment, thermosensitive poloxamer (anti-adhesion rate: 92%) was similar to Merogel (anti-adhesion rate: 89%). Evaluation of the presence and grade of adhesion, oedema, and infection in the middle meatus revealed no significant differences between the thermosensitive poloxamer group and the Merogel group at all postoperative periods. CONCLUSION: Anti-adhesive effects of thermosensitive poloxamer are similar to those of Merogel. Therefore, thermosensitive poloxamer can be considered a safe alternative to Merogel for preventing adhesion in patients undergoing endoscopic sinus surgeries, and further evaluation of thermosensitive poloxamer as an anti-adhesive and primary packing material compared with the control using no packing is needed.ope

Chronic cholesterol depletion by lovastatin suppresses MuC5AC gene expression in human airway epithelial cells

BACKGROUND: We recently showed that acute cholesterol depletion in the plasma membrane of NCI-H292 cells by methyl-β-cyclodextrin suppressed IL-1beta-induced MUC5AC gene expression. Because cholesterol depletion is clinically used as an antihypersecretory method, chronic cholesterol depletion by lovastatin is more rational and safe than acute depletion. Therefore, we sought to investigate whether chronic cholesterol depletion by lovastatin is feasible and, if so, suppresses the expression of GMUC5AC in NCI-H292 cells. We also considered whether this alteration of MUC5AC expression is related to IL-1 receptor and mitogen-activated protein kinase (MAPK) activity. METHODS: After NCI-H292 cells were pretreated with 10 μM of lovastatin for 1 hour, 10 ng/mL of IL-1β was added and cotreated with lovastatin for 24 hours. MUC5AC mRNA expression was then determined by real-time polymerase chain reaction. Cholesterol depletion by lovastatin was measured by modified microenzymatic fluorescence assay and filipin staining. The phosphorylation of IL-1 receptor, ERK, and p38 MAPK was analyzed by Western blot. RESULTS: Cholesterol in the plasma membrane was significantly depleted by lovastatin treatment for 24 hours. IL-1beta0-induced MUC5AC mRNA expression was decreased by lovastatin and this decrease occurred IL-1 receptor specifically. Lovastatin suppressed the activation of p38 MAPK but not ERK1/2 in cells activated with IL-1beta. This result suggests that lovastatin-mediated suppression of IL-1beta-induced MUC5AC mRNA operated only viathe p38 MAPK-dependent pathway. CONCLUSION: Chronic cholesterol depletion in the plasma membrane of NCI-H292 cells may be considered an antihypersecretory method, because it effectively inhibits mucin gene expression of human airway epithelial cells.ope