Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease

Park

et al. 2019

Appl Biol Chem

Repeated reflux of gastric acid and stomach contents into the esophagus leads to esophagus damage, including inflammation, ulcer, and hemorrhage in the epithelium. In this study, we aimed to demonstrate the ameliorating effects of geraniin, a phytochemical in the geraniums, on esophagus damage in an acute reflux esophagitis (RE) rat model. The inflammatory effects of geraniinwas measured by nitric oxide (NO) production and pro-inflammatory protein levels in lipopolysaccharide (LPS)-induced RAW 264.7 cells. To evaluate the protective effects of geraniin on damaged esophagus tissue in RE rats, 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 pretreated with ranitidine 30 mg/ kg body weight as a positive control. The lesion area of esophagus was determined by the Image J program, and histological changes were examined by hematoxylin and eosin staining of rat esophageal tissue. The expression of proinflammatory proteins, cytokines, and tight junction proteins involved in esophagus damages was determined using western blotting of esophageal tissue. Geraniin revealed that anti-inflammatory effects against LPS-induced cells by significantly decreasing NO production and iNOS proteins level. Additionally, the results showed that improvement effects of geraniin on esophagus 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 claudin-5) was increased in esophageal tissue. We found the potential of geraniin as source of replacement therapy products source for inflammatory and reflux esophagitis disease.

Section: Discussionmentioning

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Geraniin ameliorate experimental acute reflux esophagitis via NF-κB regulated anti-inflammatory activities in rats

Park

et al. 2019

Appl Biol Chem

“…Claudin, one of the tight junction protein in the epithelium and endothelium, exert a critical barrier function of the tight junction. In particular, claudin-4 and claudin-5 play an important role because of their tightening or sealing functions in a tissue [ 21 , 30 ]. We observed the effects of DGK on tight junction proteins of the esophageal mucosa in an RE rat model ( Figure 6 a–c).…”

Section: Resultsmentioning

confidence: 99%

“…We observed the effects of DGK on tight junction proteins of the esophageal mucosa in an RE rat model ( Figure 6 a–c). In a previous study, as esophageal erosions decreased, the expression of claudin proteins increased in the esophageal mucosa of a rat model of with GERD [ 30 ]. However, the expression of claudin-4 and claudin-5 was increased in pre-treated DGK 200 mg/kg group in a concentration-dependent manner and was significantly higher than the expression in the RE control group.…”

Section: Resultsmentioning

confidence: 99%

“…LPS has been used to study induced infection, inflammation and biochemistry of inflammatory responses [ 30 ]. To demonstrate cytotoxicity and anti-inflammatory effects of different fractions, we cultured LPS-induced Raw 264.7 cells pre-treated with fraction samples were cultured for 24 h. All fractions of Geranium koreanum showed no significant cytotoxicity on Raw 264.7 cells ( Figure 1 b).…”

Section: Discussionmentioning

confidence: 99%

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Dichloromethane Extracts of Geranium Koreanum Kom. Alleviates Esophagus Damage in Acute Reflux Esophagitis-Induced Rats by Anti-Inflammatory Activities

Choo

2018

IJMS

Reflux esophagitis (RE) is a gastrointestinal disease caused by the reflux of gastric acid and stomach contents, and it leads to esophageal damage. Therefore, it is necessary to study the improvement of esophageal damage on a RE-induced model. The present study was accomplished to demonstrate the protective effects of a dichloromethane fraction of Geranium koreanum (DGK) plant on esophageal damage in an acute RE rat model. First, we examined the potential of anti-inflammatory effects of various fractions measured by cell cytotoxicity, morphological changes and nitric oxide (NO) production on lipopolysaccharide (LPS)-induced Raw 264.7 macrophage cells. Then, to evaluate the protective effects on RE, rats were partitioned into the following groups: normal control, RE-induced control and RE rats pre-treated with DGK 100 and 200 mg/kg body weight. The esophageal mucosal ulcer ratio was measured by the Image J program and histological changes were examined using a hematoxylin and eosin staining of the esophageal mucosa. The expression of pro-inflammatory proteins, cytokines and tight junction proteins involved in the esophageal mucosal damage were investigated using Western blotting and an enzyme-linked immunosorbent assay (ELISA) kit with esophagus tissue. DGK chemical profile and phenolic contents were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). The results showed that DGK exhibited anti-inflammatory effects against LPS-stimulated cells by significantly inhibiting NO production. Additionally, the results in vivo showed that improvement effects of DGK on esophageal mucosal damage. The expression of inflammatory proteins involved in nuclear factor κB (NF-κB) signaling pathways and tight junction protein (claudin-4 and -5) were significantly decreased in esophageal mucosa. We found the potential of DGK as source of replacement therapy products for inflammatory and RE disease.

Role ofSemisulcospira gottscheiextract as medicinal food on reflux esophagitis in rats

Food Science & Nutrition

Yang

Kim

et al. 2021

Gastroesophageal reflux disease (GERD) is a globally prevalent disease and results from a reflux of gastric contents into the esophagus. Existing synthetic drug‐based treatments for GERD have various drawbacks including refractory symptoms, relapse, or resistance due to long‐term use or may result in mucosal degeneration, polyps, and osteoporosis. Semisulcospira gottschei (SE), a freshwater snail, has been generally consumed as a food source due to its excellent flavor and nutritional value in Korea and considered to have therapeutic properties for various diseases including dyspepsia, stomachache, and hepatic diseases. The present study aims to investigate whether Semisulcospira gottschei extract (SGE) has a protective effect on reflux esophagitis‐induced rat models. The anti‐inflammatory effects of SGE were evaluated via NO production in LPS‐induced Raw 264.7 macrophage. And the protection effects of SGE were analyzed by assessing the amelioration of mucosal damage and expression of inflammation‐associated proteins in reflux esophagitis (RE) rats. Our results indicate that SGE significantly suppressed NO production in LPS‐induced raw 264.7 cells without any cytotoxicity. We observed mucosal lesions and histological changes in the esophagus of RE control rats. However, SGE treatment markedly ameliorated mucosal lesion ratio indicated through histological changes. SGE administration suppressed the expression of proteins related to inflammation, such as p‐NF‐κB, p‐IκBα, COX‐2, and TNF‐α, in esophageal tissue. Moreover, SGE elevated the expression of claudin‐5, which is a tight junction protein, involved in barrier function of epithelium and endothelium. The results suggest that SGE is useful as a medicinal food in esophagitis and may be helpful in developing effective treatment protocols for GERD.