• The Korea Journal of Herbology
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• v.30 no.4
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• pp.37-44
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• 2015

Objectives : The present study was designed to evaluate the anti-inflammatory and anti-oxidative stress activities through regulation of Nrf2-mediated genes by Rhei rhizoma and Glycyrrhiza rhizoma combined extract (RGE) in reflux esophagitis.Methods : The antioxidant activity of RGE in vitro was measured in terms of radical scavenging capacity such as DPPH and ABTS. RGE was administered at 350 mg/kg body weight prior to induction of reflux esophagitis. Reflux esophagitis was induced that tied the pylorus and the transitional junction between the forestomach and the corpus in Sprague-Dawley rats.Results : RGE scavenged DPPH and ABTS effectively and IC₅₀of RGE each were 4.9 μg/ml and 45.6 μg/ml. Our results show that RGE administration markedly ameliorated mucosal damage upon histological evaluation. In serum and esophagus tissue, RGE significantly suppressed the oxidative stress biomarkers. Reflux esophagitis induced rats exhibited down-regulation of antioxidant-related proteins in the esophagus; however, the levels with treatment of RGE were significantly higher than those of vehicle reflux esophagitis rats. RGE treatment caused significant reductions in activation of NF-κB transcription factor. Thus, RGE significantly exhibited potent anti-inflammatory activities by suppressing the protein expression levels of pro-inflammatory proteins such as COX-2 and iNOS and inflammatory cytokines such as TNF-αin the esophagus tissue.Conclusions : Reflux esophagitis caused considerable levels of oxidative stress in the esophageal mucosa and the administration of RGE reduced the esophageal mucosa damage through the regulation of Nrf2 and NF-κB pathways. Our findings can considered as supplementary therapy in the prevention or treatment of reflux esophagitis.

• Korean Journal of Bronchoesophagology
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• v.8 no.1
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• pp.29-34
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• 2002

Background and Objectives : Sulfur dioxide gas is one of the major airborne Pollutants noxious to human in industrialized countries. The most vulnerable areas in the human respiratory system were the trachea and main bronchi and a gradient of decreasing damage was observed in the peripheral tracheobronchial tree. Induced functional alteration was increased mucosal permeability, and morphological changes were epithelial sloughing, intracellular edema, mitochondrial swelling, widened intercellular spaces, and ciliary cytoplamic extrusions. The laminins are a family of extracellular matrix glycoproteins localized in the basement membrane. Their primary role is cell-matrix attachment, but many additional biologic activities, including Promoting cell growth and migration, tumor growth and metastasis, wound repair, and graft survival, have been demonstrated. Materials and Methods : Histologic changes and expression of laminin in tracheal mucosa sacrificed at 1 day, 2 day, 3 day, 1 week, 2 weeks, and 3 weeks after continued SO2 exposure of 250 ppm for 30 minutes a day(to 7week) were studied in rats. In this study, mild immune reaction for laminin was noted at the apical cytoplasm of epithelial cells and basement membrane one day after a 7 week $SO_2$ exposure. The cilia and nucleoi of epithelial cells were normal and no immune reaction was noted in Goblet cells. The lamina propria of the tracheal tissue was infiltrated by monocytes and lymphocytes. Results : At 24 hours after exposure, all tracheal cells except Goblet cells revealed a mild immune reaction for laminin. No immune reactions were noted in the basement membrane. At 72 hours after exposure, mild or moderate immune reactions for laminin was seen in the tracheal cell cytoplasm. Irregular faint immune reaction for laminin was noted in the basement membrane. At 1 week after exposure, strong immune reaction for laminin was detected over all tracheal cells, and the basement membrane was seen clearly. At 2~3 weeks after exposure, strong immune reaction for laminin was seen in all tracheal epithelial cells except Goblet cells and a mild immune reaction was partly revealed in the basement membrane. Conclusion : Our study suggests that 502 produces histologic damage on the tracheal mucosa. Longer duration after exposure of $SO_2$ makes more progressive healing on the tracheal mucosa and increased immunoreactivity for laminin.

• The Korea Journal of Herbology
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• v.35 no.4
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• pp.17-23
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• 2020

Objectives : In this study, we investigated the protective effects of Charybdis japonica (C. japonica) water extract on the acute reflux esophagitis in rat models. Methods : Twenty rats were divided into four groups for examination: normal control group (n=6), the reflux esophagitis group (n=6), reflux esophagitis treated with positive control group (ranitidine 40 mg/kg, n=6), reflux esophagitis treated with C. japonica group (100 mg/kg, n=6). All rats fasted for 18 hr and then were induced with reflux esophagitis by a pylorus and forestomach ligation operation. After 4 hr, the rats were sacrificed. The proinflammatory cytokine and proteins expression measured by western bolt assay, and the histopathological analysis of the esophageal mucosa measured by hematoxylin and eosin staining. Results : C. japonica administration significantly was protecting esophageal mucosal damage upon histological analysis of reflux esophagitis in rats. The C. japonica treatment confirmed the protection of the reduction of claudin-5, an evaluation index of the damage of tight junctions in the reflux esophagitis. C. japonica was also found to inhibit the expression of proteins such as COX-2 and TNF-α in the rat esophagus. C. japonica markedly attenuated the activation of NF-κB and phosphorylation of IκBα at the same time. Conclusion : These results indicated that C. japonica suppressed the development of esophagitis through the modulation of inflammation by regulating NF-κB activation. Based on these findings, we concluded that C. japonica can prevent reflux esophagitis.

• Gut and Liver
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• v.12 no.6
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• pp.682-693
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• 2018

Background/Aims: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. Methods: The effects of $17{\beta}$-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. Results: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p<0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-${\kappa}B$, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. Conclusions: E2 acts through the estrogen receptor ${\beta}$ signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.

• Journal of Nutrition and Health
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• v.54 no.3
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• pp.321-333
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• 2021

Purpose: Reflux esophagitis is a disease caused by the reflux of stomach contents and stomach acid etc. into the esophagus due to defect in the lower esophageal sphincter and is currently increasing worldwide. This study was conducted to evaluate the effect of a mixture of Citrus Reticulata and Scutellariae Radix (CS) extract on acute reflux esophagitis in rats. Methods: Rats were divided into five groups for examination: normal group (Normal, n = 8), water-treated acute reflux esophagitis rats (Control, n = 8), tocopherol 30 mg/kg body weight-treated acute reflux esophagitis rats (Toco, n = 8), CS 100 mg/kg body weight-treated acute reflux esophagitis rats (CS100, n = 8), CS 200 mg/kg body weight-treated acute reflux esophagitis rats (CS200, n = 8). The experimental groups were administrated of each treatment compounds and after 90 min, acute reflux esophagitis was induced through surgery. Rats were sacrificed 5 h after surgery. We measured the level of reactive oxygen species (ROS) in serum and analyzed the expression of nicotinamide adenine dinucleotide phosphate, inflammatory, and tight junction-related proteins by western blot in the esophageal tissues. Results: CS administration significantly protected the esophageal mucosal damage due to reflux esophagitis, and the level of ROS in the serum was significantly reduced with CS administration as compared to Control. In addition, CS administration significantly suppressed mitogen-activated protein kinase (MAPK or MAP kinase) and nuclear factor-kappa B (NF-κB) pathways and increased protein expressions of tight junction protein. Conclusion: These results suggest that the CS not only regulates the expression of inflammatory proteins by inhibiting oxidative stress, but also reduces damage to the esophageal mucosa by inhibiting the expression of tight junction proteins.

• Radiation Oncology Journal
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• v.19 no.1
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• pp.45-52
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• 2001

Purpose : Granulocyle-colony stimulating factor (G-CSF) has been widely used to treat neutropenia caused by chemotherapy or radiotherapy. The efficacy of recombinant human hematopoietic growth factors in improving oral mucositis after chemotherapy or radiotherapy has been recently demonstrated in some clinical studies. This study was designed to determine whether G-CSF can modify the radiation injury of the intestinal mucosa in mice. Materials and Methods : One hundred and five BALB/c mice weighing 20 grams were divided into nine subgroups including G-CSF alone group $(I:10\;{\mu}g/kg\;or\;II:100\;{\mu}g/kg)$, radiation alone group (7.5 or 12 Gy on the whole body), combination group with G-CSF and radiation (G-CSF I or II plus 7.5 Gy, G-CSF I or II plus 12 Gy), and control group. Radiation was administered with a 6 MV linear accelerator (Mevatron Siemens) with a dose rate of 3 Gy/min on day 0. G-CSF was injected subcutaneously for 3 days, once a day, from day -2 to day 0. Each group was sacrificed on the day 1, day 3, and day 7. The mucosal changes of jejunum were evaluated microscopically by crypt count per circumference, villi length, and histologic damage grading. Results : In both G-CSF I and II groups, crypt counts, villi length, and histologic damage scores were not significantly different from those of the control one (p>0.05). The 7.5 Gy and 12 Gy radiation alone groups showed significantly lower crypt counts and higher histologic damage scores compared with those of control one (p<0.05). The groups exposed to 7.5 Gy radiation plus G-CSF I or II showed significantly higher crypt counts and lower histologic damage scores on the day 3, and lower histologic damage scores on the day 7 compared with those of the 7.5 Gy radiation alone one (p<0.05). The 12 Gy radiation plus G-CSF I or II group did not show significant difference in crypt counts and histologic damage scores compared with those of the 12 Gy radiation alone one (p>0,05). Most of the mice in 12 Gy radiation with or without G-CSF group showed intestinal death within 5 days. Conclusion : These results suggest that G-CSF may protect the jejunal mucosa from the acute radiation damage following within the tolerable ranges of whole body irradiation in mice.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.97-104
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• 1997

of $PLC-\gamma$ 1 activity. Results : In the immunohistochemistry, the expression of $PLC-\beta$ was negative for all grnups. The expression of $PLC-\gamma$ 1 was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of PKC-01 was strong1y positive in group I followed by group II in the damaged surface epithelium. The above findings were also confirmed in the immunoblotting study. In the irnrnunoblotting study, the expressions of $PLC-\beta,\;PLC-\gamma\;1,\;and\;PLC-\delta$ were the same as the results of immunohistochemistry The expression of ras oncoprotein was weakly Positive in groups II, III and IV. The of EGFR was the highest in the group II, III, followed by group W and the expression of PKC was weakly positive in the group II and III. Conclusion : $PLC-\gamma$ 1 mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role irL mucosal regeneration after irradiation. $PLC-\delta$ 1 mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PLC-\delta$ 1.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.79-95
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• 1997

Purpose : Phospholipase C(PLC) isozymes play significant roles in signal transduction mechanism. $PLC-\gamma$ 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. Ras oncoprotein, EGFR, and PKC are also known to be involved in cell growth. The exact mechanisms of these signal transduction following irradiation, however, were not clearly documented Thus, this study was Planned to determine the biological significance of PLC, ras oncoprotein, EGFR, and PKC in damage and regeneration of rat intestinal mucosa following irradiation. Material and Method : Sixty Sprague-Dawley rats were irradiated to entire body with a single dose of 8Gy. The rats were divided into S groups according to the sacrifice days after irradiation. The expression of PLC, ras oncoprotein, EGFR and PKC in each group were examined by the immunoblotting and immunohistochemistry. The histopathologic findings were observed using H&I stain, and the mitoses for the evidence of regeneration were counted using the light microscopy & PCNA kit. The Phosphoinositide(PI) hydrolyzing activity assay was also done for the indirect evaluation of $PLC-\gamma$ 1 activity. Results: In the immunohistochemistry , the expression of $PLC-{\beta}$ was negative for all grøups. The expression of $PLC-{\gamma}1$ was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of $PKC-{\delta}1$ was strongly positive in group 1 followed by group II in the damaged surface epithelium. The above findings were also confirttled in the immunoblotting study. In the immunoblotting study, the expressions of $PLC-{\beta}$, $PLC-{\gamma}1$, and $PKC-{\delta}1$ were the same as the results of immunohis-tochemistry. The expression of ras oncoprctein was weakly positive in groups II, III and IV. The of EGFR was the highest in the group II, III, follwed by group IV and the expression of PKC was weakly positive in the group II and III. Conclusion: $PLC-{\gamma}1$ mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role in mucosal regeneration after irradiation. $PLC-{\delta}1$ mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PKC-{\delta}1$.

• Journal of Pharmacopuncture
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• v.17 no.3
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• pp.40-49
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• 2014

Objectives: The gastric ulcer is a common disorder of the stomach and duodenum. The basic physiopathology of a gastric ulcer results from an imbalance between some endogenous aggressive and cytoprotective factors. This study examined whether Ganoderma lucidum pharmacopuncture (GLP) would provide protection against acute gastric ulcers in rats. Methods: Sprague-Dawley rats were divided randomly into 4 groups of 8 rats each: normal, control, normal saline (NP) and GLP groups. The experimental acute gastric ulcer was induced by using an EtOH/HCl solution and the normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated once with injections of saline and GLP, respectively. Two local acupoints were used: CV12 (中脘) which is the alarm point of the Stomach Meridian, and ST36 (足三里), which is the sea point of the Stomach Meridian. The stomachs from the rats in each group were collected and analyzed for gross appearance and histology. Also, immunohistochemistry staining for BAX, Bcl-2 and TGF-${\beta}1$ was performed. Results: Histological observations of the gastric lesions in the control group showed comparatively extensive damage of the gastric mucosa and necrotic lesions had penetrated deeply into the mucosa. The lesions were long, hemorrhagic, and confined to the glandular portions. The lesions were measured microscopically by using the clear depth of penetration into the gastric mucosal surface. The length and the width of the ulcer were measured and the inhibition percentage was calculated. Wound healing of the acute gastric ulcer was promoted by using GLP, and significant alterations of indices in gastric mucosa were observed. Such protection was shown by gross appearance, histology and immunohistochemistry staining for BAX, Bcl-2 and TGF-${\beta}1$. Conclusion: These results suggest that GLP administered at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol-induced acute gastric ulcer.

• Nutrition Research and Practice
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• v.9 no.6
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• pp.619-627
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• 2015

BACKGROUND/OBJECTIVES: Colitis is a serious health problem, and chronic obesity is associated with the progression of colitis. The aim of this study was to determine the effects of natural raw meal (NRM) on high-fat diet (HFD, 45%) and dextran sulfate sodium (DSS, 2% w/v)-induced colitis in C57BL/6J mice. MATERIALS/METHODS: Body weight, colon length, and colon weight-to-length ratio, were measured directly. Serum levels of obesity-related biomarkers, triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), insulin, leptin, and adiponectin were determined using commercial kits. Serum levels of pro-inflammatory cytokines including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, and IL-6 were detected using a commercial ELISA kit. Histological study was performed using a hematoxylin and eosin (H&E) staining assay. Colonic mRNA expressions of TNF-${\alpha}$, IL-$1{\beta}$, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were determined by RT-PCR assay. RESULTS: Body weight and obesity-related biomarkers (TG, TC, LDL, HDL, insulin, leptin, and adiponectin) were regulated and obesity was prevented in NRM treated mice. NRM significantly suppressed colon shortening and reduced colon weight-to-length ratio in HFD+DSS induced colitis in C57BL/6J mice (P < 0.05). Histological observations suggested that NRM reduced edema, mucosal damage, and the loss of crypts induced by HFD and DSS. In addition, NRM decreased the serum levels of pro-inflammatory cytokines, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 and inhibited the mRNA expressions of these cytokines, and iNOS and COX-2 in colon mucosa (P < 0.05). CONCLUSION: The results suggest that NRM has an anti-inflammatory effect against HFD and DSS-induced colitis in mice, and that these effects are due to the amelioration of HFD and/or DSS-induced inflammatory reactions.