• The Korea Journal of Herbology
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• v.36 no.3
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• pp.1-8
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• 2021

Objective : Reflux esophagitis (RE), one of gastroesophageal reflux disease (GERD), is a disease that causes inflammation due to reflux of stomach contents such as stomach acid and pepsin due to the unstable gastroesophageal sphincter, and is currently increasing worldwide. The currently used treatment for reflux esophagitis has various side effects. Therefore, in this study the effect of Toosendan Fructus extract on chronic acid reflux esophagitis in rats was evaluated in order to find a new treatment material for reflux treatment. Methods : After inducing reflux esophagitis through surgery, the group was separated and the drug was administered for 2 weeks; Normal rats (Normal, n=8), chronic acid reflux esophagitis rats (Control, n=8), Toosendan Fructus 200 mg/kg body weight/day-treated chronic acid reflux esophagitis rats (TF, n=8). After, we were taken esophageal tissue and esophageal mucosa damage was identified, and analyzed the expression of NADPH oxidase, AP-1/MAPK-related proteins, and tight junction proteins by western blot in esophageal tissue. Results : Toosendan Fructus administration significantly protected the esophageal mucosal damage of reflux esophagitis. Also, Toosendan Fructus significantly reduced the expression of NADPH oxidases (NOX2 and p22^phox) and AP-1/MAPK-related proteins (c-Fos, c-Jun, p-p38, p-ERK, and p-JNK). In addition, it significantly increased the expression of tight junction proteins (Occludin, Claudin-3, and Claudin-4). Conclusions : These results suggest that Toosendan Fructus reduced damage to the esophageal mucosa by protecting the esophageal mucosa by upregulating tight junctions proteins as well as inhibiting the AP-1/MAPK pathway through reducing NADPH oxidases expression.

• Korean Journal of Pharmacognosy
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• v.52 no.3
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• pp.177-185
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• 2021

Gastroesophageal reflux disease (GERD) is a gastrointestinal disorder in which stomach contents reflux into the esophagus, causing complications such as mucosal damage. The purpose of this study was to determine the effect of Rhei Rhizoma and Scutellariae Radix mixture (RS) in chronic acid reflux esophagitis (CARE), one of the GERD. After inducing reflux esophagitis through surgery, the group was separated and the drug was administered for 2 weeks; Normal rats (Normal, n=8), chronic acid reflux esophagitis rats (Control, n=8), tocopherol 30 mg/kg-treated chronic acid reflux esophagitis rats (Toco, n=8), Rhei Rhizoma and Scutellariae Radix mixture 100 mg/kg-treated chronic acid reflux esophagitis rats (RSL, n=8), Rhei Rhizoma and Scutellariae Radix mixture 200 mg/kg-treated chronic acid reflux esophagitis rats (RSH, n=8). Gross lesion of esophageal mucosa after RS treatment showed a superior enhancement compared with that of Control group. Additionally, RS significantly decreased the levels of MPO and MDA, effectively inhibited NADPH oxidase, and regulated the expression of the AMPK/LKB1/NF-κB pathway. Moreover, it significantly increased the expression of tight junction proteins. Taken together, RS not only alleviates inflammation of the esophageal mucosa via the AMPK/LKB1/NF-κB pathway by reducing oxidative stress, but also improves esophageal function by modulating tight junction proteins.

• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.577-583
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• 2018

Background/Aims Potassium-competitive acid blockers are expected to be the next generation of drugs for the treatment of diseases caused by gastric acid. In 2015, vonoprazan fumarate, a novel potassium-competitive acid blocker, was approved by the Japanese health insurance system. Since its approval, patients refractory to vonoprazan can be encountered in clinical settings. We designed this study to clarify the pathophysiology of gastroesophageal reflux disease refractory to vonoprazan. Methods In this retrospective study, we involved patients who had refractory symptoms after administration of standard-dose proton pump inhibitors or vonoprazan and underwent diagnostic testing with esophageal high-resolution manometry and 24-hour multichannel intraluminal impedance and pH monitoring while using proton pump inhibitors or vonoprazan. Patients were diagnosed based on the Rome IV criteria for functional gastrointestinal disorders and diagnostic test results. Results Twenty-seven patients were analyzed during this study. Gastric pH ${\geq}4$ was sustained for a longer period of time, and the esophageal acid exposure time and number of acid reflux events were shorter in the vonoprazan group than in the proton pump inhibitor group. The percentage of patients diagnosed with acidic gastroesophageal reflux disease in the vonoprazan group was lower than that in the proton pump inhibitor group. Conclusions Intra-gastric pH and acid reflux were strongly suppressed by 20-mg vonoprazan. When patients with gastroesophageal reflux disease present symptoms after administration of 20-mg vonoprazan, the possibility of pathophysiologies other than acid reflux should be considered.

• Korean Journal of Agricultural Science
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• v.46 no.1
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• pp.85-92
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• 2019

This study was intended to provide basic data for a health functional food study by exploring antioxidant activity of reflux extract according to the concentration of ethanol and the extract of ultrasonic waves extracted and reflux extracted under the same solvent conditions. In the same solvent condition, the reflux extract ($75.10{\pm}1.99mg$) showed a higher total phenol content than the ultrasonic wave extract ($51.74{\pm}2.28mg$). Flavonoids also had a higher reflux extract ($25.05{\pm}1.53mg$) than did ultrasonic extracts ($16.23{\pm}1.95mg$). Reflux extract according to ethanol concentration was found to have a higher phenol content than the 70% ethanol extract ($40.60{\pm}1.49mg$) in 60% ethanol extract. Flavonoid content was also similar to phenol content in reflux extract as determined by ethanol concentration from 60% ethanol ($25.05{\pm}1.53mg$) to 70% ethanol extract ($6.60{\pm}0.46mg$). In addition, the antioxidant activity (DPPH, TEAC, FRAP, ORAC) of the reflux extract in the same solvent conditions tended to be higher than that of ultrasonic extracts. Also, 60% ethanol extract had better antioxidant activity than 70% ethanol extract. However, an analysis of phenolic acid content through HPLC showed that the ultrasonic extract had a higher content in the same solvent condition than did the reflux extract. Not only the presence of phenolic acid, but also those of other compounds are believed to be attributed to the activity of antioxidants. Therefore, further studies are needed to clarify this phenomenon.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.17 no.1
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• pp.13-22
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• 2014

Esophageal pH monitoring is considered the gold standard for the diagnosis of gastroesophageal reflux disease because of the normal ranges across the pediatric age range. However, this method can only detect acid reflux. Multichannel intraluminal impedance-pH (MII-pH) monitoring has recently been used for the detection of bolus reflux in infants and children. This method allows for the detection of liquid, gas or mixed reflux in addition to acid, weakly acidic or weakly alkaline reflux. MII-pH monitoring can record the direction of flow and the height of reflux, which are useful parameters to identify an association between symptoms and reflux. However, the technique is limited by its high cost and the lack of normative data of MII-pH in the pediatric population. Despite certain limitations, MII-pH monitoring will become more common and gradually replace pH monitoring in the future, because pH monitoring is part of MII-pH.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.4 no.2
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• pp.133-141
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• 2001

Purpose: Gastroesophageal reflux (GER) has been found to be the causative factors of apnea, stridor, feeding intolerance, poor weight gain, and sudden infants death syndrome (SIDS) in infants. GER is a well-described in infants and children, but only scant mention of the premature infants with GER can be found in the literature. Methods: Esophageal pH was measured during 24 hour in 21 healthy preterm infants, using a silicone microelectrode with an external reference electrode connected to a portable recorder. The mean age of the patients was $29{\pm}8$ days, mean gestational age was $30^{+5}{\pm}2^{+0}$ weeks, mean birth weight was $1,468{\pm}329$ g, mean postconceptional age was $34^{+6}{\pm}1^{+4}$ weeks and mean weight was $1,750{\pm}329$ g. We evaluated the following reflux parameters; number of acid reflux, number of long acid reflux, longest acid reflux minutes, and reflux index. Results: Pathologic GER was detected in 12 (57%) subjects and most interesting parameters are reflux index and number of episodes with a pH<4 during 24 hour (high correlation with postprandial reflux index). Reflux was not correlated to gestational age, birth weight, age, postconceptional age, weight, sex and medication of the theophylline. Conclusion: Gastroesophageal reflux is common in preterm infants, but it is usually not apparent, even with severe reflux.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.18 no.2
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• pp.102-107
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• 2007

Laryngopharyngeal reflux disease (LPRD) is the result of retrograde flow of gastric contents to the laryngopharynx. Laryngoscopic findings and special questionnaires are first step of diagnosis of LPRD. Empiric trials of Proton pump inhibitor' test (PPI test) is recommended as treatment and diagnosis. However confirmation of reflux is then recommended primarily in patients with persistent symptoms despite acid-suppressive therapy. The 24 hour ambulatory double pH monitoring has been a gold standard method in diagnosis of LPRD even though it has some limitation. The combined multichannel intraluminal impedance and pH monitoring is a new-rising test tool. It can detect acid/non-acid, liquid/gaseous reflux and clearance of refluxate. The water siphon test is also used for diagnosis of LPRD.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.420-425
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• 2014

Esophageal reflux of gastric contents causes esophageal mucosal damage and inflammation. Recent studies show that oxygen-derived free radicals mediate mucosal damage in reflux esophagitis (RE). Chlorogenic acid (CGA), an ester of caffeic acid and quinic acid, is one of the most abundant polyphenols in the human diet and possesses anti-inflammatory, antibacterial and anti-oxidant activities. In this context, we investigated the effects of CGA against experimental RE in rats. RE was produced by ligating the transitional region between the forestomach and the glandular portion and covering the duodenum near the pylorus ring with a small piece of catheter. CGA (10, 30 and 100 mg/kg) and omeprazole (positive control, 10 mg/kg) were administered orally 48 h after the RE operation for 12 days. CGA reduced the severity of esophageal lesions, and this beneficial effect was confirmed by histopathological observations. CGA reduced esophageal lipid peroxidation and increased the reduced glutathione/oxidized glutathione ratio. CGA attenuated increases in the serum level of tumor necrosis factor-${\alpha}$, and expressions of inducible nitric oxide synthase and cyclooxygenase-2 protein. CGA alleviates RE-induced mucosal injury, and this protection is associated with reduced oxidative stress and the anti-inflammatory properties of CGA.

• The Korea Journal of Herbology
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• v.34 no.2
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• pp.15-23
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• 2019

Objective : Reflux esophagitis (RE) is a disease that caused gastric acid reflux and inflammation due to unstable gastroesophageal sphincter, as increasing worldwide respectively. This study was conducted to evaluate the effect of Evodiae Fructus (EF) extract on chronic reflux esophagitis in rats. Methods : The EF was measured antioxidant activity, such as total polyphenol and total flavonoid contents, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethyl-enzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity. Rats were divided into 3 groups; Nor (normal group), Con (chronic acid reflux esophagitis rats treatment with water), EF (chronic acid reflux esophagitis rat treatment with EF 200 mg/kg body weight group). A surgically-induced chronic acid reflux esophagitis (CARE) model was established in SD rats, and treated with water or EF 200 mg/kg body weight for 14 consecutive days. Results : Administration of EF to rats of induction of chronic acid reflux esophagitis was found to reduce esophagus tissues injury. Reactive oxygen species (ROS) and produces peroxynitrite ($ONOO^-$) levels of esophagus tissues were significantly decreased in EF compared to Con group. As results of esophagus protein analyses, EF effectively reduce inflammatory-related factors ($NF-{\kappa}Bp65$, $p-I{\kappa}B{\alpha}$, iNOS, $TNF-{\alpha}$, IL-6), and increase anti-oxidant enzyme (Nrf2, HO-1, SOD, catalase, GPx-1/2). Conclusions : These results suggest that EF administration comfirmed that decreased esophagus tissues injury, oxidantive stress, anti-inflammation effect, and increased anti-oxidant effect. Therefore, EF was the potential to be used as a natural therapeutic drug.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.14 no.1
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• pp.26-29
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• 2003

Background and Objectives : Gastric acid reflux has been suggested to have an association with sleep apnea(SA). This study's aim is to evaluate the relationship between reflux laryngitis and SA through the fact that the treatment of reflux laryngitis may impact the snoring and SA related symptoms in selective individuals. Methods : Population consist of 24 males and 10 female aged 34 to 66 years(mean age 50 years) confirmed by Reflux Finding Score(RFS) of PC Belafsky. Thirty four patients with reflux laryngitis and associated symptoms of SA were treated with proton pump inhibitor(Rabeprazole sodium 10mg/day) for 60 days. The degree of snoring and apnea related symptoms were evaluated using questionnaires, and palatine tonsillar hypertropy(PTH) and RFS were compared preoperatively and postoperatively. Results : After antireflux treatment for 60 days, the snoring(p=0.039), daytime sleepiness(p=0.002), and concentration(p=0.011) were significantly improved(p<0.05) and RFS was significantly decreased(p=0.000), but morning headache(p=0.057) and sleep apnea(p=0.083) were not significantly improved(p>0.05) and PTH was not significantly decreased(p=0.328). Conclusion : Treatment of reflux laryngitis significantly impacted the snoring, daytime sleepiness, and concentration in selective individuals. These results suggest some close relationship between reflux laryngitis and SA, and the treatment of reflux laryngitis may be some effective in those with both disorders.