• 대한본초학회지
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• 제36권3호
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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.

• 생약학회지
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• 제52권3호
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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.

• 대한본초학회지
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• 제34권2호
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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.

• 대한본초학회지
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• 제34권1호
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• pp.117-124
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• 2019

Objective : Chronic acid reflux esophagitis (CARE), one of gastroesophageal reflux disease (GERD) is increasing worldwide. Coptidis rhizoma extract (CRE) is a traditional herb that cures a variety of diseases. This study was conducted to evaluate the protective effect of CR on rats with chronic acid reflux esophagitis. Methods : The antioxidant activities were evaluated through radical scavenging assays using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) radical scavenging assays. CARE was surgically induced in 5-week-old male SD rats by ligating the border between forestomach and glandular portion with a 2-0 silk tie and covering the duodenum using 18-Fr $N{\acute{e}}laton$ catheter. To evaluate the esophageal protective effect of CRE, rats were divided into 3 groups: Nor (normal rats), Veh (chronic acid reflux esophagitis induced rats), CR (chronic acid reflux esophagitis induced rats treated with CRE 200 mg/kg body weight). Results : The administration of CRE significantly prevented the mucosal injury of the esophagus tissue and histological findings improved the esophageal lesion. It has been shown that inflammation is prevented by the increase of antioxidant-related factors (Nrf-2, HO-1, SOD, catalase, and GPx-1/2) through the antioxidant pathway of esophageal tissue. The administration of CRE reduced the increase of serum peroxynitrite ($ONOO^-$) and markedly reduced the protein expression of inflammatory mediator such as $NF-{\kappa}Bp65$, $p-I{\kappa}B{\alpha}$, iNOS, and IL-6. Conclusions : Overall, these results suggest that CRE administration confirmed the protective effect of esophageal mucosa, suggesting that it is a potential treatment for chronic acid reflux esophagitis.

• 대한의생명과학회지
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• 제27권2호
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• pp.77-87
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• 2021

Reflux esophagitis (RE) is a disease that stomach contents, stomach acid, and pepsin continually refluxing and is curently increasing worldwide. This study was conducted to find natural materials that can reduce side effects and effectively treat RE. Animal experiments were conducted with a 1:1 (EA1), 1:5 (EA5) ratio of Evodiae Fructus and Arecae Semen known to be effective against reflux esophagitis. As a result of confirming the total lesion of the esophageal mucosa after EA1 or EA5 treatment in reflux esophagitis animals, it showed superior improvement compared to the RE-control rats. In addition, by regulating the expression of MPO and NADPH oxidase, the activation of NF-κB was inhibited, and the expression of COX-1 and COX-2 was regulated. Moreover, its improved esophageal barrier function through regulating protein expressions of tight junction protein and MMPs/TIMPs. Taken together, a mixture of Evodiae Fructus and Arecae Semen can attenuate the damage to the esophageal mucosa that not only inactivationed the NF-κB through oxidative stress control, but also by regulating tight junctions and MMPs/TIMPs. This effect was more excellent in the 1:1 mixture (EA1) than in the Evodiae Fructus and Arecae Semen 1:5 mixture (EA5).

• 생약학회지
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• 제51권4호
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• pp.349-359
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• 2020

Gastroesophageal reflux disease (GERD) is a disease that stomach contents continually refluxing, and is currently on the rise worldwide. The purpose of this study is to find natural materials that can reduce side effects and effectively treat chronic acid reflux esophagitis (CARE), one of GERD. First, the antioxidant activity was confirmed by varying the mixing ratio of Coptidis Rhizoma and Evodiae Fructus, which are effective against chronic reflux esophagitis. After, animal experiments were conducted using a 1:1 (CE) and 1:2 (CEE) combination ratio of Coptidis Rhizoma and Evodiae Fructus, which had the best antioxidant efficacy. Gross lesion of esophageal mucosa after CE or CEE treatment showed a superior enhancement compared with that of CARE control rats. Additionally, its inhibited MAPK phosphorylation and led NF-κB inactivation through the suppression of IκBα phosporylation by regulating Nrf2/Keap-1, and NF-κB inactivation induced reduced protein expressions including inflammatory mediators and cytokines. Moreover, its improved esophageal barrier function through upregulating protein expressions of tight junction protein, whereas downregulating protein expressions of MMPs. Taken together, a mixture of Coptidis Rhizoma and Evodiae Fructus can attenuate the esophageal mucosal ulcer by inhibiting MAPK and NF-κB pathway, and upregulating proteins associated with tight junction.

• 대한한방내과학회지
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• 제42권5호
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• pp.800-807
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• 2021

Objectives: This study investigated the efficacy of Korean medical treatment for reflux esophagitis. Methods: We used Korean medical treatment (herbal medicines, acupuncture, herbal acupuncture, and therapy) to treat a hospitalized patient with reflux esophagitis. To evaluate the treatment, we measured the symptoms using the Reflux Symptom Index (RSI) and the Visual Analogue Scale (VAS) for heartburn, acid reflux, chest pain, foreign body sensations in the throat, chronic cough, hoarseness, and bronchial asthma. The generic health status was evaluated using the European Quality of Life Five-Dimension (EQ-5d) Scale. Results: The RSI and EQ-5d scores improved following treatment, but the VAS scores showed that only heartburn, acid reflux, and chest pain symptoms were relieved. Conclusions: This study suggests that Korean medicine may be effective for treating reflux esophagitis.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 추계학술대회
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• pp.41-46
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• 1997

Lower esophageal sphincter (LES) is characterized by the ability to maintain a sustained pressure, and to relax allowing the passage of a bolus, whereas the esophagus is normally relaxed and contracts only briefly when required to produce peristalsis (fig. 1). The neuromuscular mechanisms that participate in the physiological regulation of these functions are not well understood, but it is thought that LES tone is spontaneous and regulated mostly through myogenic mechanisms, whereas LES relaxation and esophageal contraction are induced by neural mechanisms. Gastroesophageal reflux represents the effortless movement of gastric contents from stomach to esophagus. Because this phenomenon occurs in virtually everyone multiple times every day and in the majority of people without clinical consequences, the reflux per se is not disease. However in some cases, it can be pathologic, producing symptoms and signs called gastroesophageal reflux disease (GERD), which mechanism is not well known. It may result in heart burn, chronic esophagitis, aspiration pneumonia, esophageal strictures, and Barrett's esophagus.

• 대한본초학회지
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• 제35권4호
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• pp.25-36
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• 2020

Objective : Reflux esophagitis is a disease caused by the reflux of gastric acid and inflammation due to unstable gastroesophageal sphincter. The aim of the present study was to clarify the effect of Phellodendri Cortex (PC) on chronic reflux esophagitis (CRE) in rats. Methods : The anti-oxidant activity of PC was measured by total polyphenol, total flavonoid contents, 1, 1-diphenyl-2-picrylhydrazyl (DPPH), and 2, 2'-azinobis-3-ethyl-enzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity. A CRE was established surgically in SD rats. And then CRE rats were treated with water or PC 200 mg/kg body weight for 14 days. Besides, the anti-oxidant and inflammatory protein levels were evaluated using western blotting. Results : PC reduced esophagus tissues injury. The total polyphenol (36.05 ± 0.25 mg/g) and total flavonoid (72.90 ± 0.61 mg/g) of PC showed a high content. PC strongly reduced radical scavenging activities (DPPH IC₅₀ 43.58 ± 1.54 ㎍/㎖; ABTS IC₅₀ 36.75 ± 0.35 ㎍/㎖). Moreover, reactive oxygen species (ROS) and peroxynitrite (ONOO^-) levels in serum, the protein expression of inducible nitric oxide synthases (iNOS) were significantly reduced. In addition, the protein expression of NADPH oxidases related to oxidative stress were significantly reduced in PC compared to CRE control. PC effectively reduced inflammatory factors including, TNF-α, and IL-6 via NF-κBp65 inactivation through the inhibition of p-IκBα and increased anti-oxidant enzyme such as HO-1, SOD, catalase, and GPx-1/2 via Nrf2 activation. Conclusions : Taken together, these results show that PC can alleviate the esophageal mucosal ulcer though the inhibition of NF-κB inflammatory and the enhancement of Nrf2 anti-oxidant pathway.

• 대한한방내과학회지
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• 제42권6호
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• pp.1245-1254
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• 2021

Objectives: This study investigated the clinical characteristics and symptoms of patients with reflux esophagitis (RE) visiting a Korean medicine hospital. Methods: We retrospectively reviewed the medical records of patients with an RE diagnosis who visited a Korean medicine hospital from June 15, 2020, to April 15, 2021. We analyzed the clinical characteristics and the results of a symptoms questionnaire. Results: Our sample included 1,151 patients (711 females). The median age was 58 years; the most common age bracket was 60-69 years. A total of 837 patients (72.7%) presented with symptoms lasting more than one year, and 1,035 (89.9%) had been prescribed medications for more than three months before visiting a Korean medicine hospital. Belching (77.6%) and acid regurgitation (70.9%) were the most frequent symptoms, followed by epigastric pain (61.6%) and throat globus (58.5%). Throat globus was the most bothersome symptom, and 72.4% of the patients experienced the symptom on more than five days in the preceding two weeks. Patients with a longer symptom duration were older (p<0.01) and more likely to be overweight (p=0.03). Patients experiencing symptoms for more than five years were more likely to report throat globus (p=0.02), hoarseness (p<0.01), and coughing (p<0.01). Conclusions: Most RE patients visiting a Korean medicine hospital were females in their sixties with chronic and refractory RE. Atypical symptoms (belching, epigastric pain, and throat globus) were common. Throat globus was highly prevalent in severe cases, suggesting that it warrants attention when treating RE patients.