• Journal of Pharmaceutical Investigation
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• v.27 no.2
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• pp.99-108
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• 1997

To evaluate the feasibility of mucosal delivery of thyrotropin releasing hormone (TRH) through various mucosae, enzymatic degradation and stabilization of TRH in the nasal, rectal and duodenal extracts of rabbits were studied. TRH in the extracts was assayed by HPLC and its degradation was found to follow apparent first-order kinetics. The residual concentrations of TRH in the mucosal extracts of nasal, rectal and duodenal segments after 24 hr of incubation were found to be $65.1({\pm}1.1),\;19.7({\pm}2.7)$ and 0%, and in the serosal extracts, $65.6({\pm}5.5),\;75.2({\pm}1.1)$ and $68.7({\pm}1.4)%$, respectively. This result suggests that there is a significant difference in the activity of TRH-degrading enzymes among the sites of administration. The inhibition of TRH degradation in the mucosa extracts was kinetically investigated using various additives such as thimerosal, benzalkonium chloride, disodium edetate, ${\sigma}-phenanthroline$, dithiothreitol and dithioerythritol, and $IC_{50}$ values of inhibitors were calculated. The results obtained showed that thimerosal (0.5 mM) and benzalkonium chloride (0.141 mM) protected TRH from the enzymatic degradation in all the mucosa extracts more than 95% after 24 hr of incubation.

• YAKHAK HOEJI
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• v.38 no.5
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• pp.530-543
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• 1994

To study the feasibility of transmucosal delivery of leucine enkephalin (Leu-Enk) and $[D-ala^2]$-leucine enkephalinamide (YAGFL), their degradation extents and pathways in various rabbit mucosa extracts were investigated by high performance liquid chromatography. The degradation of Leu-Enk and YAGFL was observed to follow the first-order kinetics. The degradation half-lives of Leu-Enk in the nasal, rectal and vaginal mucosal extracts were 1.62, 0.37 and 1.12 hrs and those of YAGFL were 30.55, 9.70 and 6.82 hrs, respectively, indicating Leu-Enk was degraded in a more extensive and rapid manner than YAGFL. But the mucosal and serosal extracts of the same mucosa showed the similar degradation rates for both pentapeptides. The degradation was most rapid in the neutral pH and increasing concentrations of substrates retarded the degradation rates. The maior hydrolytic fragments of Leu-Enk were Des-Tyr-Leu-Enk and tyrosine, indicating the enzymatic hydrolysis by aminopeptidases. However, the data also suggested endopeptidases such as dipeptidyl carboxypeptidase and dipeptidyl aminopeptidase could play some role in the degradation of Leu-Enk. On the other hand, the hydrolytic fragments of YAGFL in all the mucosa extracts were mainly Tyr-D-Ala-Gly and Phe-Leu-Amide, demonstrating the hydrolytic breakdown by endopeptidases. The degradation pathways were further explored by concomitantly determining the formation of smaller metabolites of primary hydrolytic fragments of Leu-Enk and YAGFL in the mucosa extracts.

• Toxicological Research
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• v.34 no.2
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• pp.97-102
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• 2018

The objective of this study was to determine the oral wound healing effects of acai berry water extracts (ABWE) in rat oral mucosa. To estimate the anti-oxidative effects of ABWE, the contents of phenolic compounds, and DPPH (1,1-diphenyl-2-picryl hydrazyl) and ABTS (2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) abilities were evaluated. Wound healing effects of ABWE were tested following 6-day exposure after induction of wound by applying 50% acetic acid to oral mucosa of Sprague-Dawley rats. Macroscopic and histopathological analyses were performed to determine wound healing effects of ABWE. Sodium fusidate (20 mg/g) was used as positive control. ABWE showed significantly high antioxidant effects in all assays, although its potency was weaker than the positive control. From day 3 after treatment, wound healing effects of ABWE were observed in oral mucosa. These wound healing effects were also consistent with histopathological evaluation results. Taken together, these results indicate that ABWE might have potential as an oral wound healing agent in the future.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.4
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• pp.257-265
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• 2016

The aim of this study was to investigate the effects of Ulmi Pumilae cortex extracts on acute reflux esophagitis rats induced by pylorus and forestomach ligation operation. 40 rats were divided into five groups; Normal group, Sham group, Control group, T1 group and T2 group. 4 groups has a laparotomy after controled 2weeks and sham group, T1 group, T2 group has ligation in stomach. After laparotomy, all group`s body weight, gastric volume, gastric juice PH, SOD activities, catalase activities, lipid peroxidation, total glutathione, the effects on esophageal and stomach mucosa damage were checked. There was significant statistical differences between control group and Ulmi Pumilae cortex extracts adminitration groups(T1 and T2 group) in terms of gastric volume decreasing. Also, adminitration groups has significant effect than control group in decreasing mucosa damage. SOD(superoxide dismutase) and catalase activities has a significant statistical differences between control group and T2 group not in T1 group. These results suggest that the medication of Ulmi Pumilae cortex extracts is effective for the treatment of acute reflux esophagitis in terms of decerasing gastric volume and mucosa damage. Especially, the results were shown to be more positive in High-dose administration group (T2 group) than in Low-dose administration group (T1 group) in SOD and catalase activities.

• The Journal of Pediatrics of Korean Medicine
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• v.34 no.4
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• pp.31-42
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• 2020

Objectives The purpose of this study is to perform a review on recent researches of Hataedock, a traditional method of removing fetal toxin by dropping herbal extracts in the mouth, to appraise its preventive and therapeutic effects of diseases. Methods Studies of Hataedock were extracted from both Chinese and Korean medical journals published within 10 years, from January 2010 to January 2020. Clinical studies and experimental researches were analyzed and categorized to skin disease, allergic rhinitis, intestinal mucosa inflammation and anal fistula for further evaluation. Results Among 194 studies were searched and screened, 22 met designated criteria. Hataedock showed the effectiveness in treating skin disease, allergic rhinitis, intestinal mucosa inflammation and anal fistula by maintaining skin barrier and regulating immune system. Coptis japonica, Glycyrrhiza uralensis, and Fermented Glycine max were mainly used as herbal extracts in Hataedock. Conclusion This study shows the recent research trends of Hataedock and suggests that Hataedock can be considered as a method of treatment or prevention to some of the incurable chronic diseases.

• The Journal of Pediatrics of Korean Medicine
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• v.29 no.3
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• pp.54-64
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• 2015

Objectives : This study was to investigate the anti-oxidative and anti-inflammatory effect of Lonicera japonica water extracts (LE) on Ulcerative Colitis Induced by DSS (Dextran Sulfate Sodium) in Mice. Methods : Colitis was induced by DSS in Balb/c mice. The sample group was divided into three. The mice in control group were not inflammation-induced. The pathological group was composed of untreated colitis elicited mice. The experimental group was administered Lonicera japonica water extracts (LE) after colitis elicitation. The effects on ulcerative colitis were evaluated the anti-oxidant effect, inhibition of COX-2 mRNA expression, the morphological change of colonic mucosa, decrease effect of HSP 70 and COX-2 in mucosa. Results : The SOD ability of LE was dose-dependently increased and the LPS-induced COX-2 mRNA expression of LE was dose-dependently decreased. LE showed the protective effects on DSS-induced experimental colitis. LE inhibited shortening of colon length, the hemorrhagic erosion in colonic mucosa. LE also showed the decrease effect for HSP70 and COX-2 in mucosa. Conclusions : The current results demonstrate the clinical utility of LE in traditional medicine and indicate the possible treatments for ulcerative colitis from natural products. Further investigations for exact mechanisms will be needed.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.1
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• pp.71-77
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• 2011

Gastric ulcer has multifactorial etiology, and the development of ulcer is known to be caused by gastric acidity, pepsin secretion, gastric motility and gastric mucosal blood flow. The ulcer results from the tissue necrosis and apoptotic cell death triggered by mucosal ischemia, free radical formation and cessation of nutrient delivery. The gastric mucosa is usually exposed to a wide range of aggressive insults, and has developed efficient mechanisms to repair tissue injury. The apoptotic process of gastric mucosa is triggered by the induction of such proapoptotic gene expression, such as BAX. The Bcl-2 family of proteins plays a pivotal role in the regulation of apoptosis. The maintenance of gastric mucosa integrity depends upon the ratio between cell proliferation and cell death. Stress-inducing factors may affect Bcl-2/BAX ratio and thus the rate of apoptosis through modulation of the expression of both proteins depends upon the experimental model. In addition to the regulation of apoptosis, new vessels have to be generated in order to ensure an adequate supply of oxygen and nutrients to the healing gastric mucosa. This events are regulated by several factors. Among them, such polypeptide growth factors, such as vascular endothelial growth factor (VEGF) regulates essential cell functions involved in tissue healing including cell proliferation and differentiation. The purpose of this study was carried to investigate whether Rhei Rhizoma administration might protect apoptotic cell death and promote angiogenesis in gastric mucosa. Sprague-Dawley rats were randomly divided into 4 groups; normal, saline, cimetidine and Rhei Rhizoma-treated group. The saline, cimetidine and Rhei Rhizoma extracts were orally administrated to each group and gastric ulcer was induced by HCl-EtOH solution. After 1 hour, the stomachs were collected for histological observation and immunohistochemistry. In results, Rhei Rhizoma proves to promote to heal wound in gastric ulcer in conclusion and the significant changes of BAX, Bcl-2 and VEGF quantity in gastric mucosa were observed. These results suggest that Rhei Rhizoma extract may promote incision wound healing and has protective effects on gastric ulcer in rats.

• Korean Journal of Food Science and Technology
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• v.37 no.1
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• pp.84-89
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• 2005

Mongolian dandelion (Taraxacum mongolicum H.) extracted with solvents having different polarities were prepared to investigate protection activity of gastric mucosa. Ethanol extracts were successively reextracted with methylene chloride, and n-butanol. Concentrations of total flavonoids and luteolin in n-butanol extracts were 27.75 and 1.14%, respectively, much higher than those of other solvent extracts. Results of anti-microbial acitivity test against Helicobacter pylori and urease inhibition test revealed n-butanol extract exerted higher inhibition (13.16%) than other solvent extracts. Based on 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, n-butanol extract showed the highest efficiency of free radical-scavenger activity among the extracts ($SC_{50}\;47{\mu}g/mL$). Erythrocytic photohemolysis tests, for the protection of cell membrane showed that half-life of human erythrocytes was increased by the addition of n-butanol extract $({\tau}_{50}=172min;C=5.0{\mu}g/mL)$. These results indicate n-butanol extract of Mongolian dandelion may be useful as a adjuvant for gastric diseases.

• Journal of Pharmaceutical Investigation
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• v.26 no.3
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• pp.175-185
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• 1996

To inhibit the enzymatic degradation of leucine enkephalin (Leu-Enk) and its synthetic analog. $[D-ala^2]$-leucine enkephalinamide (YAGFL), in the nasal, rectal and vaginal mucosal and serosal extracts of rabbits, effects of enzyme inhibitors such as amastatin (AM), puromycin (PM), thiorphan (TP), thimerosal (TM), EDTA, N-carboxymethyl-Phe-Leu (CPL), phenylethyl alcohol (PEA), phenylmercuric acetate (PMA), benzalkonium chloride (BC) and modified cyclodextrins, alone or in combination, were observed by assaying the pentapeptides staying intact during incubation. Mucosa extracts were prepared by exposing freshly-excised mucosal specimens mounted on Valia-Chien cells to isotonic phosphate buffer while stirring. The degradation of Leu-Enk and YAGFL followed the apparent first-order kinetics. The half-lives (mean) in the nasal, rectal and vaginal mucosal extracts were found to be 1.07, 0.33 and 1.14 hr for Leu-Enk, and 16.9, 6.2 and 6.8 hr for YAGFL, respectively. AM or PM, which is an aminopeptidase inhibitor, did not show a sufficient inhibition of Leu-Enk $(50\;{\mu}g/ml)$ degradation in all kinds of extracts. $Dimethyl-{\beta}-cyclodextrin\;(DM-{\beta}-CyD)$ decreased the degradation rate constants of Leu-Enk about 2 or 3 times, comparing with no additive. However, the use of mixed inhibitors of AM $(50\;{\mu}M)$/TM (0.25 mM)/EDTA (5 mM) resulted in a full stabilization of Leu-Enk by decreasing the degradation rate constants 67.3, 161.3 and 113.8 times far the nasal, rectal and vaginal mucosal extracts, respectively, comparing with no inhibitor. With mixed inhibitors, Leu-Enk remained intact more than 90% after 6 hr-incubation. In the stabilization of YAGFL, hM, TP or CPL alone showed little efffct, and some additives demonstrated a considerable inhibition of YAGFL degradation in the rank order of TM > BC > EDTA. However, the addition of mixed inhibitors such as TM (0.5 mM) and EDTA (5 mM) into the extracts protected YAGFL from the degradation by more than 85% even after 24 hr-incubation, suggesting almost complete inhibition of YAGFL degradation in the extract. On the other hand, $DM-{\beta}-CyD\;or\;hydroxypropyl-{\beta}-cyclodextrin$ (10%) were also found to retard enzymatic degradation rates of YAGFL markedly, and resulted in staying intact more than 80% of YAGFL in the nasal and vaginal mucosal extracts, and more than 60% in the rectal mucosal extract after 16 hr-incubation.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.173-183
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• 1992

To study the feasibility of transmucosal delivery of $[D-ala^2]-methionine$ enkephalinamide (YAGFM), its enzymatic degradation and stabilization in various rabbit mucosal extracts were investigated by HPLC method. The degradation of YAGFM was observed to follow the first-order kinetics and the half-lives of YAGFM in the nasal, rectal and vaginal mucosal extracts were found to be 25.7, 3.0 and 7.8 hr, respectively. However, there was no significant difference in degradation rates of YAGFM between the mucosal and serosal extracts obtained from the same mucosal membrane. This finding suggests that even a synthetic enkephalin analog, which is designed to be resistent to aminopeptidases, needs to be fully protected from the enzymatic degradation in mucosal sites for the delivery of the analog through mucosal routes. To inhibit the degradation of YAGFM in various mucosal extracts, effects of enzyme inhibitors such as bestatin (BS), amastatin (AM), thiorphan (TP), thimerosal (TM) and EDTA, alone or in combination, and modified cyclodextrins were observed by assaying YAGFM staying intact during 24 hr-incubation at $37^{\circ}C$. It was found from the results that mixed inhibitors such as TM (0.5 mM)/EDTA (5 mM) or AM $(50{\mu}M)/TM$ (0.5 mM)/EDTA (5 mM) provided very useful means for the stabilization in various mucosal extracts. The latter was found to protect YAGFM from the degradation in the nasal, rectal, and vaginal mucosal extracts by 90.9, 90.4 and 91.3%, respectively, after 24 hr-incubation, suggesting almost complete inhibition of YAGFM-degrading enzymes present in the incubation mixture. However, BS $(50{\mu}M)$, AM 50 $(50{\mu}M)$ or TP$(50{\mu}M)$ alone did not reveal sufficient inhibition except TM (0.5 mM) or EDTA (5 mM). The adddition of $2-hydroxylpropyl-{\beta}-cyclodextrin$(10%) to the nasal mucosal extract, and $dimethyl-{\beta}-cyclodextrin$(10%) to the rectal and vaginal mucosal extracts reduced the first-order rate constants for the degradation of YAGFM by 5.8, 17.3 and 8.9 times, respectively, compared to those with no additive.