Reflux esophagitis (RE), one of the gastroesophageal reflux disease (GERD), has recently come to be considered as a critical clinical problem it caused by the repeated reflux of gastric acid and stomach contents into the esophagus. Histamine type (H2) antagonists and proton pump inhibitors (PPIs) ar...
Reflux esophagitis (RE), one of the gastroesophageal reflux disease (GERD), has recently come to be considered as a critical clinical problem it caused by the repeated reflux of gastric acid and stomach contents into the esophagus. Histamine type (H2) antagonists and proton pump inhibitors (PPIs) are the most conventionally used healing for RE disease. These drugs have an obvious effect and easy accessibility, though it were limited by the relapse, incomplete mucosal treatment, symptoms and several side effects such as hepatotoxicity and degradation of bacteriocidal actions in long-time administration. The phytoconstituents from plant have a various benefic activity and plant-derived bio-medicines are recently regarded to be the safety replacement therapy to treat various diseased conditions. Therefore, the study was conducted to demonstrate the anti-inflammatory and protective effects of Geranium koreanum extracts (in Chapter Ⅰ), and the fraction isolated from Geranium koreanum (in Chapter Ⅱ) and the Geraniin (in Chapter Ⅲ) on esophagus in RE induced rats.
CHAPTER Ⅰ Ameliorating Effects of Geranium koreanum Kom. on Esophageal Damage in Reflux Esophagitis via NF-kB Signaling-mediated Anti-inflammatory Activities
Geranium koreanum, an herbaceous perennial plant, is widely used as a Chinese herbal medicine to treat various diseases. To demonstrate the anti-inflammatory effects of Geranium koreanum extracts on esophageal mucosal damage in acute reflux esophagitis (RE)-induced rats. The anti-inflammatory effects of Geranium koreanum were first examined on lipopolysaccharide (LPS)-induced Raw 264.7 macrophage cells. Also, the contents of Geraniin compound in Geranium koreanum measured by HPLC analysis. To evaluate the improvement of RE, rats were divided into the following groups: normal, RE-induced, and RE rats pre-treated with Geranium koreanum 100 and 200 mg/kg body weight. The esophageal mucosal ulcer ratio and histological changes were examined using the Image J program and hematoxylin and eosin staining of the rat esophageal mucosa, respectively. Geranium koreanum exhibited anti-inflammatory effects against LPS-stimulated cells by significantly inhibiting nitric oxide (NO) production and inducible NO synthase (iNOS) protein expression. Additionally, the LPS-induced morphological transformation of cells was recovered following pre-treatment with Geranium koreanum. The Geranium koreanum 200 mg/kg extract-treated group was protected against LPS-stimulation. The inflammatory mechanism (nuclear factor [NF]-kB and mitogen-activated protein kinases [MAPK] signaling pathways) involved in the esophageal damage was investigated using western blotting with esophagus tissue, and Geranium koreanum clearly inhibited the inflammatory response in esophagitis-induced rats. This study demonstrates the anti-inflammatory and ameliorating effects of Geranium koreanum in acute RE.
CHAPTER Ⅱ Ameliorating Effects of Dichloromethane Fraction of Geranium koreanum Kom. on Esophageal Damage in Reflux Esophagitis via NF-kB Signaling-mediated Anti-inflammatory Activities
Reflux esophagitis is a gastrointestinal disease caused by the reflux of gastric acid and stomach contents. In this study, we demonstrate the protective effects of dichloromethane (DICHO) fraction of the Geranium koreanum plant on esophageal mucosal damages in an acute reflux esophagitis (RE) rat model. Four different solvent fractions (hexane, dichloromethane, ethyl acetate and butanol) were extracted from Geranium koreanum 70% ethanol extracts. DICHO’s chemical profile and phenolic contents were analyzed using liquid chromatography-mass spectrometry. We also examined whether various fractions had anti-inflammatory effects by measuring cell cytotoxicity, morphological changes, and nitric oxide (NO) production in lipopolysaccharide (LPS)-induced Raw 264.7 macrophage cells. Rats were divided into the following groups to evaluate the protective effects on RE: normal control, RE-induced control, and RE rats pre-treated with DICHO fraction of Geranium koreanum 100 and 200 mg/kg body weight. The esophageal mucosal ulcer ratio was measured using the Image J program, and histological changes were examined using hematoxylin and eosin staining of the rat esophageal mucosa. We evaluated the expression of pro-inflammatory proteins, cytokines, and tight junction proteins involved in esophageal damage using western blotting with esophagus tissue. DICHO fraction of Geranium koreanum exhibited anti-inflammatory effects against LPS-stimulated cells by significantly inhibiting NO production. We also found that it improved esophageal tissue damage. The expression of inflammatory proteins involved in nuclear factor NF-kB signaling pathway was significantly decreased and tight junction proteins (claudin-4 and -5) were increased in the esophageal mucosa.
CHAPTER Ⅲ Geraniin Ameliorate Experimental Acute Reflux Esophagitis via NF-kB Regulated Anti-inflammatory Activities in Rats
Repeated reflux of gastric acid and stomach contents into the esophagus leads to mucosal damage, including inflammation, ulcer, and hemorrhage in the epithelium. In this study, we aimed to demonstrate the ameliorating effects of geraniin, a phytochemical derived from geraniums, on esophageal mucosal damage in an acute reflux esophagitis (RE) rat model. The inflammatory effects of geraniin was measured by nitric oxide (NO) production and pro-inflammatory protein levels in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. In addition, we observed cytotoxicity and morphological alterations in macrophage cells. To evaluate the protective effects of geraniin on damaged esophageal mucosa in RE rat model, the rats were divided into the following groups: normal control; RE-induced control; RE rats pretreated with geraniin 15 and 30 mg/kg body weight; and RE rats pre-treated with ranitidine 30 mg/kg body weight as a positive control. The lesion area of esophageal mucosa was determined by the Image J program, and histological changes were examined by hematoxylin and eosin staining of rat esophageal tissue. The expression of pro-inflammatory proteins, cytokines, and tight junction proteins involved in esophageal damages was determined using western blotting of esophageal tissue. Geraniin revealed that anti-inflammatory effects against LPS-stimulated cells by significantly decreasing NO production iNOS proteins level. Additionally, the results showed that improvement effects of Geraniin on esophageal damages in RE induced rats. The expression of inflammatory proteins involved in nuclear factor NF-kB signaling pathways significantly decreased and tight junction protein (claudin-4 and -5) was increased in esophagus. We found the potential of Geraniin as source of replacement therapy products source for inflammatory and reflux esophagitis disease.
Reflux esophagitis (RE), one of the gastroesophageal reflux disease (GERD), has recently come to be considered as a critical clinical problem it caused by the repeated reflux of gastric acid and stomach contents into the esophagus. Histamine type (H2) antagonists and proton pump inhibitors (PPIs) are the most conventionally used healing for RE disease. These drugs have an obvious effect and easy accessibility, though it were limited by the relapse, incomplete mucosal treatment, symptoms and several side effects such as hepatotoxicity and degradation of bacteriocidal actions in long-time administration. The phytoconstituents from plant have a various benefic activity and plant-derived bio-medicines are recently regarded to be the safety replacement therapy to treat various diseased conditions. Therefore, the study was conducted to demonstrate the anti-inflammatory and protective effects of Geranium koreanum extracts (in Chapter Ⅰ), and the fraction isolated from Geranium koreanum (in Chapter Ⅱ) and the Geraniin (in Chapter Ⅲ) on esophagus in RE induced rats.
CHAPTER Ⅰ Ameliorating Effects of Geranium koreanum Kom. on Esophageal Damage in Reflux Esophagitis via NF-kB Signaling-mediated Anti-inflammatory Activities
Geranium koreanum, an herbaceous perennial plant, is widely used as a Chinese herbal medicine to treat various diseases. To demonstrate the anti-inflammatory effects of Geranium koreanum extracts on esophageal mucosal damage in acute reflux esophagitis (RE)-induced rats. The anti-inflammatory effects of Geranium koreanum were first examined on lipopolysaccharide (LPS)-induced Raw 264.7 macrophage cells. Also, the contents of Geraniin compound in Geranium koreanum measured by HPLC analysis. To evaluate the improvement of RE, rats were divided into the following groups: normal, RE-induced, and RE rats pre-treated with Geranium koreanum 100 and 200 mg/kg body weight. The esophageal mucosal ulcer ratio and histological changes were examined using the Image J program and hematoxylin and eosin staining of the rat esophageal mucosa, respectively. Geranium koreanum exhibited anti-inflammatory effects against LPS-stimulated cells by significantly inhibiting nitric oxide (NO) production and inducible NO synthase (iNOS) protein expression. Additionally, the LPS-induced morphological transformation of cells was recovered following pre-treatment with Geranium koreanum. The Geranium koreanum 200 mg/kg extract-treated group was protected against LPS-stimulation. The inflammatory mechanism (nuclear factor [NF]-kB and mitogen-activated protein kinases [MAPK] signaling pathways) involved in the esophageal damage was investigated using western blotting with esophagus tissue, and Geranium koreanum clearly inhibited the inflammatory response in esophagitis-induced rats. This study demonstrates the anti-inflammatory and ameliorating effects of Geranium koreanum in acute RE.
CHAPTER Ⅱ Ameliorating Effects of Dichloromethane Fraction of Geranium koreanum Kom. on Esophageal Damage in Reflux Esophagitis via NF-kB Signaling-mediated Anti-inflammatory Activities
Reflux esophagitis is a gastrointestinal disease caused by the reflux of gastric acid and stomach contents. In this study, we demonstrate the protective effects of dichloromethane (DICHO) fraction of the Geranium koreanum plant on esophageal mucosal damages in an acute reflux esophagitis (RE) rat model. Four different solvent fractions (hexane, dichloromethane, ethyl acetate and butanol) were extracted from Geranium koreanum 70% ethanol extracts. DICHO’s chemical profile and phenolic contents were analyzed using liquid chromatography-mass spectrometry. We also examined whether various fractions had anti-inflammatory effects by measuring cell cytotoxicity, morphological changes, and nitric oxide (NO) production in lipopolysaccharide (LPS)-induced Raw 264.7 macrophage cells. Rats were divided into the following groups to evaluate the protective effects on RE: normal control, RE-induced control, and RE rats pre-treated with DICHO fraction of Geranium koreanum 100 and 200 mg/kg body weight. The esophageal mucosal ulcer ratio was measured using the Image J program, and histological changes were examined using hematoxylin and eosin staining of the rat esophageal mucosa. We evaluated the expression of pro-inflammatory proteins, cytokines, and tight junction proteins involved in esophageal damage using western blotting with esophagus tissue. DICHO fraction of Geranium koreanum exhibited anti-inflammatory effects against LPS-stimulated cells by significantly inhibiting NO production. We also found that it improved esophageal tissue damage. The expression of inflammatory proteins involved in nuclear factor NF-kB signaling pathway was significantly decreased and tight junction proteins (claudin-4 and -5) were increased in the esophageal mucosa.
CHAPTER Ⅲ Geraniin Ameliorate Experimental Acute Reflux Esophagitis via NF-kB Regulated Anti-inflammatory Activities in Rats
Repeated reflux of gastric acid and stomach contents into the esophagus leads to mucosal damage, including inflammation, ulcer, and hemorrhage in the epithelium. In this study, we aimed to demonstrate the ameliorating effects of geraniin, a phytochemical derived from geraniums, on esophageal mucosal damage in an acute reflux esophagitis (RE) rat model. The inflammatory effects of geraniin was measured by nitric oxide (NO) production and pro-inflammatory protein levels in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. In addition, we observed cytotoxicity and morphological alterations in macrophage cells. To evaluate the protective effects of geraniin on damaged esophageal mucosa in RE rat model, the rats were divided into the following groups: normal control; RE-induced control; RE rats pretreated with geraniin 15 and 30 mg/kg body weight; and RE rats pre-treated with ranitidine 30 mg/kg body weight as a positive control. The lesion area of esophageal mucosa was determined by the Image J program, and histological changes were examined by hematoxylin and eosin staining of rat esophageal tissue. The expression of pro-inflammatory proteins, cytokines, and tight junction proteins involved in esophageal damages was determined using western blotting of esophageal tissue. Geraniin revealed that anti-inflammatory effects against LPS-stimulated cells by significantly decreasing NO production iNOS proteins level. Additionally, the results showed that improvement effects of Geraniin on esophageal damages in RE induced rats. The expression of inflammatory proteins involved in nuclear factor NF-kB signaling pathways significantly decreased and tight junction protein (claudin-4 and -5) was increased in esophagus. We found the potential of Geraniin as source of replacement therapy products source for inflammatory and reflux esophagitis disease.
주제어
#Esophagus Geraniin Geranium koreanum Inflammation in vitro in vivo Reflux esophagitis
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