• 대한한의학방제학회지
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• 제31권4호
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• pp.389-413
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• 2023

Objectives : This study aimed to review the current trends in experimental studies on the use of natural products for treatment of gastroesophageal reflux disease (GERD). Methods : Experimental studies assessing the efficacy of natural products against GERD were searched on PubMed. Articles were selected based on predefined inclusion and exclusion criteria and then analyzed for experimental methods, interventions, and result analysis techniques. Results : A total 37 studies were included in this review. Predominantly, in vivo experiments were conducted to induce GERD through surgery, involving the ligation of the pylorus and the transitional junction between the corpus and the forestomach using 7-week-old male Sprague-Dawley rats. The acute induction model, sacrificing animals after a single administration following GERD induction, was mainly used.The utilization of cell experiments was relatively infrequent, with a focus on assessing antioxidant and anti-inflammatory effects via the treatment of the RAW 264.7 cell line with lipopolysaccharides treatment. Glycyrrhizae Radix et Rhizoma, Pinelliae Tuber, Ginseng Radix and Zingiberis Rhizoma were used as single ingredients, and herbal formula, STW-5 (iberogast), Rikkunshito (六君子湯), Banhasasim-tang (半夏瀉心湯), and Hewei Jiangni granule (和胃降逆湯) were used. Outcome analysis methods encompassed Macroscopic evaluation, esophageal function assessment, blood biomarker analysis, histological examination, protein analysis, gene expression analysis, and gastric juice analysis. Proton pump inhibitors were predominantly employed as positive controls. Conclusions : This study revealed the current trends in non-clinical research evaluating natural products for GERD. Based on the results of this study, we expect that non-clinical research on clinically effective natural products will be revitalized.

• 대한본초학회지
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• 제30권4호
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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.

• 대한한방내과학회지
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• 제37권3호
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• pp.495-507
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• 2016

Objectives: This study was designed to investigate the effects of Jwa Kum-Whan (JKW) on reflux esophagitis in rats.Methods: Forty rats were divided into five groups: a sham group (with no medication and only treated with ventrotoby); a group with reflux esophagitis (RE); a pantoprazole group (treated with 30 mg/kg pantoprazole per day for two weeks); a JKW280 group (treated with 280 mg/kg JKW per day for two weeks); and a JKW560 group (treated with 560 mg/kg JKW per day for 2 weeks). All rats fasted for 24 hrs and then were induced with RE by the oral administration of indomethacin and by a pylorus and forestomach ligation operation. After 8 hrs, the rats were sacrificed. We measured body weight, gastric juice pH, gastric volume, antioxidant activity, and cytokine and made a histologic examination of the esophagus and the stomach.Results: The weights of the rats in each group were not significantly different. The gastric juice pH significantly increased in the JKW560 group and the pantoprazole group compared with the RE group. Gastric volume significantly decreased in the JKW560 group compared with the RE group and the pantoprazole group. SOD activities significantly increased in the JKW280 and JKW560 groups compared with the RE group. Catalase activities significantly increased in the pantoprazole group and the JKW560 group compared with the RE group. TNF-α significantly decreased in the JKW280 and JKW560 groups compared with the RE group. IL-6 significantly decreased in the pantoprazole group and the JKW280 and JKW560 groups compared with the RE group. Histologic examination of the esophagus and the stomach showed significant improvements in the pantoprazole, JKW280, and JKW560 groups compared with the RE group.Conclusion: Based on these results, it is concluded that JKW can prevent reflux esophagitis.

• 대한본초학회지
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• 제35권4호
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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.

• 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.

• 대한본초학회지
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• 제35권1호
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• pp.57-68
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• 2020

Objective : The aim of present study was to clarify the effect of Areca Semen and Toosendan Fructus Mixture (AT-mix) on chronic reflux esophagitis (CRE) in rats. Methods : The antioxidant activity of AT-mix was measured through DPPH and ABTS radical scavenging activities in vitro. CRE was induced in SD rats (5 weeks, male) by ligating the border forestomach and granular portion with 2-0 silk and the duodenum near the pyloric portion was covered with 2-mm wide piece of 18-Fr Nélaton catheter. And then rats were treated AT-mix 200 mg/kg one daily for 14 days. The anti-oxidant and inflammatory protein levels were evaluated using western blotting. Results : Gross lesion of esophageal mucosa after AT-mix treatment showed a superior enhancement compared with that of CRE control rats. AT-mix treatment strongly reduced both DPPH and ABTS radical scavenging activities (DPPH, IC₅₀ 8.15±0.14 ㎍/mL; ABTS, IC₅₀ 24.69±0.03 ㎍/mL, repspectively). Levels of the NADPH oxidase subunit including NOX4 and p22^phox increased in CRE control rats. Otherwise, AT-mix treatment significantly reduced. The activation of Nuclear factor-erythroid 2-related factor 2 (Nrf2) led to significantly the up-regulation of HO-1. The inhibition of IκBα phosphorylation led to NF-κB inactivation. Subsequently, NF-κB inactivation significantly induced the decrease of COX-2, iNOS, TNF-α, and IL-6 protein expressions. Conclusion : Taken together, these results suggest that AT-mix treatment can attenuate the esophageal mucosal ulcer though inhibiting NF-κB pathway and enhancing Nrf2/HO-1 pathway. Thus, the additional mechanism study about AT-mix would need for the development as a safe herbal therapy for CRE.