The Review of Domestic Research on Traditional Korean Medicine for Gastroesophageal Reflux Disease

Nam Hyun seo; Nam, Hyun seo

doi:10.13048/jkm.23018

JKM > Volume 44(2); 2023 > Article

seo: The Review of Domestic Research on Traditional Korean Medicine for Gastroesophageal Reflux Disease

Original Article

The Journal of Korean Medicine 2023; 44(2): 70-105.

DOI: https://doi.org/10.13048/jkm.23018

The Review of Domestic Research on Traditional Korean Medicine for Gastroesophageal Reflux Disease

Nam Hyun seo

College of Oriental Medicine, Sangji University

Correspondence to: Hyun seo, Nam, Gangwon-do wonju city sangjidae-gil 83, College of Oriental Medicine, Sangji University, Tel: +82-10-9527-5568, E-mail: fpahs3366@naver.com

Received April 6, 2023 Revised April 20, 2023 Accepted May 10, 2023

Abstract

This study was conducted to examine the current status of traditional korean medicine studies on gastroesophageal reflux disease in Korea, identify deficiencies, and suggest the direction of future medicine research methods to lay the foundation for traditional korean medicine treatment. All domestic papers on the korean traditional treatment of gastroesophageal reflux disease were selected among the literature published until August 2022 in six domestic databases. A total of 52 selected research data were classified into experimental research papers, clinical research papers, and review papers. In experimental papers, to evaluate the effectiveness of treatment, improvement of esophageal mucosal lesions, anti-inflammatory mechanisms, antioxidant mechanisms, esophageal mucosal protection mechanisms, gastric peristalsis control, and gastric acid secretion inhibition mechanisms were used as evaluation measures. In the clinical research paper, the basis for diagnosis of cases was clinical symptoms through medical history listening and diagnosis through visits to hospitals in the past. The average treatment period was 40.7 days, and the duration of treatment was not significantly affected by the duration of the disease. The most widely used Korean medicine treatment intervention was herbal medicine. There were 3 literature review studies, 3 systematic literature review and meta-analysis studies, 1 comparative review study for clinical trial guideline development, all using Chinese papers. This study included all domestic papers on gastroesophageal reflux disease to identify the research trend of the Korean oriental medicine community, and based on this, it is meaningful to confirm areas that need to be supplemented in future research plans.

Keywords: Gastroesophageal reflux syndrome, Reflux gastritis, Herbal medicine, Acupuncture, Review

Fig. 1

Flow diagram of the selection process.

Table 1

The List of In Vivo/Vitro Studies

Author	Year	Title	Journal
Nam HH17)	2022	Crab Water Extrct Amelorates Reflux Esophagitis in Rats	Herbal Formula Science
Lee SH18)	2021	The Protective Effect of Arecae Semen and Coptidis Rhizoma in a Chronic Reflux Esophagitis Rat Model	J. Int. Korean Med
Lee JA19)	2021	Effects of a mixture of Citri Pericarpium and Scutellariae Radix on acuterefluxesophagitisinrats	J Nutr Health
Lee JA20)	2021	Effect of Toosendan Fructus on Chronic Acid Reflux Esophagitis Rats	Kor. J. Herbology
Lee JA21)	2020	Effect of a Mixture of Rhei Rhizoma and Scutellariae Radix Extract on Acute Reflux Esophagitis Rat	Kor. J. Herbol.
Lee SH22)	2020	The Protective Effect of Water Extract of Phellodendri Cortex in Chronic Reflux Esophagitis-induced Rats	Kor. J. Herbol.
Lee JA23)	2020	Effect of Coptidis Rhizoma and Evodiae Fructus Mixture on Esophageal Mucosa in Chronic Reflux Esophagitis	Kor. J. Pharmacogn.
Nam HH24)	2020	Effect on rat model of reflux esophagitis treated with Charybdis japonica extract	Kor. J. Herbol.
Shin MR25)	2020	The protective effect of Areca Semen and Toosendan Fructus mixture in a chronic model of reflux esophagitis	Kor. J. Herbol.
Lee SH26)	2019	A Comparative Study on the Effects of Pinellia ternata, Zingiber officinale and Sobanhatang on Reflux Esophagitis	J Korean Med
Lee JA27)	2019	Evaluation of Evodiae Fructus Extract on the Chronic Acid Reflux Esophagitis in Rat	Kor. J. Herbology
Kim SH28)	2019	Improving Effects on Rats with Chronic Acid Reflux Esophagitis Treated of Coptidis Rhizoma Extract	Kor. J. Herbology
Song CH29)	2018	A Comparative Study of Sepiae Os, Arcae Concha, Ostreae Concha and Esomeprazole in a Mouse Model of Reflux Esophagitis	J Korean Med
Kwon OJ30)	2016	Improving Effects on Rats with Reflux Esophagitis Treated with Combined Extract of Young persimmon fruit and Citrus peel	Kor. J. Herbol.
Shin MH31)	2016	Suppressive Effects of Ulmi Pumilae Cortex Extracts on the Reflux Esophagitis in Rat	Korean J. Oriental Physiology & Pathology
Lee JY32)	2016	Improving effect of Artemisiae Capillaris Herba extract in reflux esophagitis rats	Kor. J. Herbology
Shin MK33)	2016	Effects of Jwa Kum-Whan on Reflux Esophagitis in Rats	J. Int. Korean Med

Lee SK34)	2016	The Administration of Jeungmiyijin-tang to Rats with Induced Gastro Reflux Esophagitis	J. Int. Korean Med
Kim MY35)	2015	Improving Effect of a Combined Extract of Rhei Rhizoma and Glycyrrhizae Rhizoma through Anti-oxidative Stress in Reflux Esophagitis rats	Kor. J. Herbol.
Lee ST36)	2013	Effects of Individual Herbal Components of Yijintang-gamibang in the Rat Reflux Esophagitis	J. Int. Korean Med
Choi YJ37)	2013	Inhibitory Effects of Naegwan-acupuncture(PC6) on Acute Reflux Esophagitis Rat	Journal of Korean Acupuncture & Moxibustion Medicine Society
Jang MW38)	2013	Experimental Study for Effect of Banhasasim-tang on Mice with Reflux Esophagitis	J. Int. Korean Med
Kim DJ39)	2012	Effect on Acute reflux Esophagitis by Evodiae Fructus Aquous Extracts	Kor. J. Herbology

Kim HJ40)	2010	Effects of Yijintang-gamibang on Reflux Esophagitis Induced by Pylorus and Forestomach Ligation in Rats	J. Int. Korean Med
Lee YJ41)	2020	Effects on Rats with Reflux Esophagitis Treated with Lonicerae Flos Extract	Korean J. Oriental Physiology & Pathology
Park K42)	2010	Protective Effects of Yijin-tang-gamibang Aqueous Extracts on Reflux Esophagitis Mediated by Antioxidant Defense System	Korean J. Oriental Physiology & Pathology

Table 2

The List of Clinical Researches

Author	Year	Title	Journal
Case report
Kim MS43)	2021	A Case Report of Taeumin Patient with Gastroesophageal reflux disease Treated with Taeumin Cheongsimyeonja-tang	J. Sasang Constitut Med
Kim SW44)	2021	A Case Report on Reflux Esophagitis Treated with Korean Medicine in a Patient with Spinal Stenosis	J. Int. Korean Med
Jun HJ45)	2020	A Case Report of Non-cardiac Chest Pain in a Non-erosive Reflux Disease Patient Treated with Beewha-eum	J. Int. Korean Med
Na GY46)	2017	A Case Report on Soojeom-san plus Jeungmiyijin-tang for Treatment of Gastroesophageal Reflux Disease with Hiatal Hernia	J. Int. Korean Med
Lee JH47)	2017	Clinical Case Report of PPI-refractory Gastro-Esophageal Reflux Disease (GERD) with Korean Medicine Treatment - A Focus on Evaluation of the Abdominal Examination	J. Int. Korean Med
Yoon SH48)	2016	A Clinical Case Report of Endoscopic Reflux Esophagitis with Gastric Dysmotility Treated with Korean Traditional Medical Therapy	J. Int. Korean Med
Kim YJ49)	2016	A Case Report of Gastroesophageal Reflux Disease and Dysphagia Caused by Ingestion of Detergent	J. Int. Korean Med
Kim YH50)	2011	A Case Study of Taeumin Patient with Gastro-esophageal reflux disease(GERD) who Treated Successfully with Yeoldahanso-tang(Reduohanshao-tang)	J. Sasang Constitut Med
Park JW51)	2006	A Clinial Case Report of Non-erosive Reflux Disease Treated with Traditional Oriental Medicine	J. Int. Korean Med
Lee JE52)	2005	A Case Report of Gastroesophageal Reflux(GERD) with Hiatal Hernia	J. Int. Korean Med
Baek DG53)	2004	Clinical Study on 1 Case of Reflux Esophagitis	Korean J. Oriental Physiology & Pathology
Case series
Lee JH54)	2017	Case Study of Three Gastro-esophageal Reflux-induced Chronic Cough Patients Treated with Ojeok-san plus Saengmaek-san	J. Int. Korean Med
Ha NY55)	2017	Case Series of Refractory Gastroesophageal Reflux Disease Treated with Lijin-tang-gamibang	J. Int. Korean Med
Lim TH56)	2015	2 Case Reports of Gastroesophageal Reflux Disease Diagnosed as Soyangin Mangeum	J. Sasang Constitute Med
Kim MJ57)	2015	A Case Study of 4 Patients with Reflux Esophagitis Who Had Improved Gastroesophageal Reflux Disease after Treatment with SokPyeonAnGel	J. Int. Korean Med
Kim BS58)	2005	Seven Cases of Non-Erosive Gastroesophageal Reflux Disease Who were Treated by Lijintang-Gamibang and Acupuncture	J. Int. Korean Med
Assessment scales study
Han GJ59)	2015	Development of a Standard Tool for Pattern Identification of Gastroesophageal Reflux Disease(GERD)	J. Int. Korean Med
Choi YJ60)	2022	A Study of the Reliability and Validity of Standard Tools for the Pattern Identification of Gastroesophageal Reflux Diseas	J. Int. Korean Med
Comparative study
Baek SY61)	2019	Comparison of the Clinical Characteristics of Patients with Gastroesophageal Reflux Disease According to Globus Sensation	J. Int. Korean Med

Table 3

In Vivo/Vitro Studies about Gastroesophageal Reflux Disease on Traditional Medicine

Author (year)	Animal	Medication	Route & period	main outcome measures	Results
Nam17) (2022) vitro, vivo	Sprague-Dawley Rats (n=18) Pylorus and forestomach ligation operation-induced RE lipopolysaccharide induced Raw 264.7 cell	crab water extract (CWE)	Oral pre-treated with 100 mg/kg CWE 1h before surgery	① NO production (cell) ② esophageal mucosa damage area ③ COX-2, TNF-α ④ NF-κB, IκB-α	① suppressed ② decreased ③ decreased ④ decreased
Lee18) (2021) vitro, vivo	Sprague-Dawley Rats (n=not reported)	Arecae Semen and Coptidis Rhizoma mixture (AC-mix) 1:2.5	Oral (1회/day), 2 weeks	① total polyphenol, total flavonoid ② DPPH, ABTS scavenging activity ③ esophageal mucosa damage area ④ NF-κBp65 ⑤ COX-2, iNOS ⑥ HO-1, Nrf2-Keap1 ⑦ MMP-2 ⑧ TIMP-1, TIMP-2	① showed a high content ② high antioxidant activities ③ reduced ④ inhibited ⑤ inhibited ⑥ increased ⑦ decreased ⑧ elevated
Lee19) (2021) vitro, vivo	Sprague-Dawley Rats (n=40) Pylorus and forestomach ligation operation-induced RE	Citri Pericarpium and Scutellariae Radix (CS) 1:1	Oral pre-treated 90 min before surgery	① esophageal mucosal damage area ② ROS ③ NADPH (NOX4, P47 phox) ④ MAPK (c-Fos, c-Jun, p-p38, p-ERK, p-JNK) ⑤ NF-κBp65, p-IκBα, COX-2, TNF-α, IL-6 ⑥ claudin-1, claudin-4	① reduced ② reduced ③ reduced ④ reduced ⑤ reduced ⑥ increased
Lee20) (2021) vitro, vivo	Sprague-Dawley Rats (n=16) Pylorus and forestomach ligation operation-induced RE	Toosendan Fructus	Oral (1회/day),2 weeks	① total polyphenol, total flavonoid ② esophageal mucosal damage area ③ NADPH oxidases, AP-1/MAPK (c-Fos, c-Jun, p-p38, p-ERK, p-JNK) ④ Occludin, Claudin-3, Claudin-4	① showed a high content ② reduced ③ reduced ④ increased
Lee21) (2020) vitro, vivo	Sprague-Dawley Rats (n=40) Pylorus and forestomach ligation operation-induced RE	Mixture of Rhei Rhizoma and Scutellariae Radix Extract 1:1	Oral pre-treated before surgery	① esophageal mucosal damage area ② ROS, AST, ALT ③ NADPH, MAPK, NF-κBp65, p-IκBα, COX-2, TNF-α, IL-6, IL-4, IL-10 ④ Claudin-1, Claudin-3, Claudin-4	① reduced ② reduced ③ reduced ④ increased
Lee22) (2020) vitro, vivo	Sprague-Dawley Rats (n=not reported) Pylorus and forestomach ligation operation-induced RE	Water Extract of Phellodendri Cortex	Oral (1회/day), 2 weeks	① esophageal mucosal damage area ② total polyphenol, total flavonoid ③ DPPH, ABTS radical scavenging activities ④ ROS, ONOO-, iNOS ⑤ NADPH oxidases : NOX4, p47phox, p22phox ⑥ TNF-α, IL-6, NF-κBp65, p-IκBα ⑦ HO-1, SOD, catalase, GPx-1/2, Nrf2	① reduced ② showed a high content ③ high antioxidant activities ④ reduced ⑤ reduced ⑥ reduced ⑦ increased
Lee23) (2020) vitro, vivo	Sprague-Dawley Rats (n=not reported) Pylorus and forestomach ligation operation-induced RE	Coptidis Rhizoma and Evodiae Fructus Mixture 1:1, 1:2	Oral (1회/day), 2 weeks	① DPPH, ABTS radical scavenging activities ② esophageal mucosal damage area. ③ NADPH Oxidase (NOX4, p47phox) ④ Nrf2, Keap-1 ⑤ MAPKs (c-Fos, c-Jun, p-p38, p-ERK, p-JNK) ⑥ NF-κBp65, p-IκBα iNOS, COX-2, TNF-α, IL-6 ⑦ MMP-2, MMP-8 ⑧ ZO-1, occludin, claudin-1, claudin-4	① high antioxidant activities ② reduced ③ reduced ④ increased ⑤ reduced ⑥ reduced ⑦ reduced ⑧ reduced
Nam24) (2020) vitro, vivo	Sprague-Dawley Rats (n=20) Pylorus and forestomach ligation operation-induced RE	Charybdis japonica extract	Oral pre-treated before surgery	① esophageal mucosal damage 4area ② claudin-5 ③ COX-2, TNF-, NF-κB, p-IκBα	① reduced ② protected ④ reduced
Shin25) (2020) vitro, vivo	Sprague-Dawley Rats (n=not reported) Pylorus and forestomach ligation operation-induced RE	Areca Semen and Toosendan Fructus mi5xture	Oral (1회/day), 2 weeks	① DPPH, ABTS radical scavenging activity ② esophageal mucosal damage area ③ NADPH oxidase (NOX4, p22phox) ④ Nrf2, HO-1, SOD, Catalase, GPx-1/2 ⑤ NF-κB(p-IκBα, NF-κBp65), COX-2, iNOS, TNF-α, IL-6	① high antioxidant activities ② reduced ③ reduced ④ increased ⑤ decreased
Lee26) (2019) vitro, vivo	Sprague-Dawley Rats (n=60) Pylorus and forestomach ligation operation-induced RE	Pinellia ternata (PT), Zingiber officinale (ZE), Sobanhatang water extract (SBT)	Oral (1회/day), 2 weeks	① DPPH radical scavenging activity ② HO-1 ③ ghrelin ④ gastrin ⑤ substance P ⑥ mucosal barrier damage ⑦ distribution of mast cells and inflammatory cells	① increased, Ascorbic acid > ZE > PT > SBT ② increased, ZT > SBT > PT ③ increased, ZT> ET > SBT ④ decreased, PT > SBT ⑤ decreased, PT > SBT ⑥ decreased, PT > SBT > ZT ⑦ decreased, ZT > SBT > PT
Lee27) (2019) vitro, vivo	Sprague-Dawley Rats (n=not reported) Pylorus and forestomach ligation operation-induced RE	Evodiae Fructus Extract	Oral (1회/day), 2 weeks	① Total polyphenol, total flavonoid ② DPPH, ABTS radical scavenging activity ③ esophagus mucosal damage area ④ ROS, ONOO- ⑤ NF-κBp65, p-IκBα, iNOS, TNF-α, IL-6 ⑥ Nrf2, HO-1, SOD, catalase, GPx-1/2	① showed high contents ② high antioxidant activities ③ reduced ④ decreased ⑤ reduced ⑥ increased
Kim28) (2019) vitro, vivo	Sprague-Dawley Rats (n=not reported) Pylorus and forestomach ligation operation-induced RE	Coptidis Rhizoma Extract	Oral (1회/day), 2 weeks	① DPPH, ABTS radical scavenging activity ② esophagus mucosal damage area ③ Nrf-2, HO-1, SOD, catalase, GPx-1/2 ④ ONOO-, NF-κBp65, p-IκBα, iNOS, IL-6.	① high antioxidant activities ② improved ③ increased ④ reduced
Song29) (2018) vitro, vivo	RAW 264.7 cell BALB/c Rats (n=50) induced by gastric juice	Sepiae Os, Arcae Concha, Ostreae Concha	Oral (1회/day), 2 weeks	① NO production, iNOS mRNA expression level(vitro) ② iNOS, p-IκB, TNF-α ③ serotonin ④ esophagus mucosal damage area ⑤ IL-6	① decreased ② suppressed (SOT,OCT) ③ increased (ACT,MT,OCT) ④ less (SOT,ACT,OCT) ⑤ suppressed (SOT,OCT)
Kwon30) (2016) vitro, vivo	Sprague-Dawley Rats (n=24) Pylorus and forestomach ligation operation-induced RE	Combined Extract of Young persimmon fruit and Citrus peel	Oral pre-treated before surgery	① esophageal mucosa damage area ② ROS, ONOO- ③ SOD, catalase, GPx ④ COX-2, iNOS, TNF-α, IL-6 ⑤ NFκB, p-IκBα	① decreased ② decreased ③ increased ④ reduced ⑤ decreased
Shin31) (2016) vitro, vivo	Sprague-Dawley Rats (n=40) Pylorus and forestomach ligation operation-induced RE	Ulmi Pumilae Cortex Extracts	Oral (1회/day), 2 weeks	① Gastric volume ② Mucosa damage ③ SOD, catalase	① decreased ② decreased ③ increased.
Lee32) (2016) vitro, vivo	Sprague-Dawley Rats (n=24) Pylorus and forestomach ligation operation-induced RE	Artemisiae Capillaris Herba extract	Oral pre-treated before surgery	① Total polyphenol and total flavonoid ② DPPH, ABTS radical scavenging activity ③ ROS, p-IκBα, NF-κBp65, COX-2, iNOS, TNF-α ④ esophageal mucosa damage area.	① high contents ② high antioxidant activities ③ decreased ④ decreased
Shin33) (2016) vitro, vivo	Sprague-Dawley Rats (n=40) Pylorus and forestomach ligation operation-induced RE	Jwa Kum-Whan (Coptidis Rhizoma 240g, Evodiae Fructus 40g)	Oral (1회/day), 2 weeks	① gastric juice pH ② gastric volume ③ SOD, Catalase ④ TNF-α, IL-6 ⑤ esophageal mucosa damage area	① increased ② decreased ③ increased ④ decreased ⑤ decreased
Lee34) (2016) vitro, vivo	Sprague-Dawley Rats (n=12) Pylorus and forestomach ligation operation-induced RE	Jeungmiyijin-tang (Pinelliae Rhizoma 4 Citri Pericarpium 4 Holelen 4 Gardeniae Fructus 4 Coptidis Rhizoma 4 Cyperi Rhizoma 4 Ponciri Fructus Immaturus 3 Cnidii Rhizoma 3 Atractylodis Rhizoma 3 Paeoniae Radix 3 Massa Medicata Fermentata 2 Glycyrrhizae Radix 1)	Oral (1회/day), 2 weeks	① esophageal mucosa damage area ② mast cells, IL-1β, TNF-α, MMP-9. ③ Apoptosis	① decreased ② reduced ② decreased
Kim35) (2015) vitro, vivo	Sprague-Dawley Rats (n=18) Pylorus and forestomach ligation operation-induced RE	Combined Extract of Rhei Rhizoma and Glycyrrhizae Rhizoma 15g	Oral pre-treated before surgery	① DPPH, ABTS scavenging activity ② esophageal mucosa damage area ③ ROS, ONOO-, TABARS ④ Nrf2, HO-1 ⑤ IκBα, NF-κB p65, COX-2, iNOS, TNF-α, IL-6	① high antioxidant activities ② reduced ③ decreased ④ increased ⑤ decreased
Lee36) (2013) vitro, vivo	Sprague-Dawley Rats (n=88) Pylorus and forestomach ligation operation-induced RE	Individual Herbal Components of Yijintang-gamibang (Pinella Rhizoma, Citri Pericarpium, Holelen, Atractylodis Rhizoma, Massa Meicata Fermentata, Hordei Fructus Germiniatus, Coptidis Rhizoma, Glycyrrhizae Radix)	Oral pre-treated twice (1hr before and 6hrs after surgery)	①esophageal mucosa damage area ②gastric volumes ③gastric acid and pepsin outputs ④MDA, SOD, GSH ⑤total hexose, sialic acid	① decreased ② decreased ③ decreased ④ increased ⑤ increased (only in CP,H, AR,HFG,CR,GR)
Choi37) (2013) vivo	Sprague-Dawley Rats (n=27) Pylorus and forestomach ligation operation-induced RE	Naegwan-acupuncture(PC6)	Four times an hour after surgery	① death rate ② gastric volume, gastric juice pH, gastric injury, esophageal mucosa injury ③ TNF-α, IL-6, MCP-1	① decreased ② decreased ③ decreased
Jang38) (2013) vitro, vivo	ICR Rats (n=30) 50% ethyl alcohol-induced RE	Banhasasim-tang (Pinelliae Rhizoma 12 Scutellariae Radix 6 Zingiberis Rhizoma 6 Ginseng Radix 6 Glycyrrhizae Radix 6Jujubae Fructus 6 Coptidis Rhizoma 2)	Oral (1회/day), 3 days	① The migration of inflammation-related cells in GEJ ② ghrelin, substance P, iNOS ③ esophageal mucosa damage area	① decreased ② decreased ③ decreased
Kim39) (2012) vitro, vivo	Sprague-Dawley Rats (n=24) Pylorus and forestomach ligation operation-induced RE	Evodiae Fructus Aquous Extract	Oral pre-treated before surgery	① esophageal damage percentage. ② TNF-α, IL-1, IL-1β, and IL-6	① decreased ② decreased
Park40) (2010) vitro, vivo	Sprague-Dawley Rats (n=56) Pylorus and forestomach ligation operation-induced RE	Yijin-tang-gamibang Aqueous Extract ( Ephedrae Herba 16 Cinnamomi Ramulus 8 Platycodi Radix 8 Fritillariae Bulbus 8 Armeniacae Semen 8 Schizandrae Fructus 8 Gelatinum 8 Aurantii Immaturi Pericarpium 4)	Oral (1회/day), 28 days	①Esophageal Lipid Peroxidation ② SOD, catalase, GSH ③ total hexose, sialic acid ④ histamine, collagen content ⑤ esophageal mucosa damage area	① suppressed ② increased ③ increased ④ decreased ⑤ decreased
Kim41) (2010) vivo	Sprague-Dawley Rats (n=56) Pylorus and forestomach ligation operation-induced RE	Yijintang-gamibang (Pinelliae Tube 16 Aurantii nobilis Pericarpium 8 Poria 8 Atractylodis Rhizoma 8 Massa Medicata Fermentat 8 Hordei Fructus Germinatus 8 Coptidis Rhizoma 8Glycyrrhizae Radix 4)	Oral (1회/day), 28 days	① esophageal mucosa damage area ② gastric volume ③ acid and pepsin output.	① decreased ② decreased ③ decreased
Lee42) (2010) vitro, vivo	Sprague-Dawley Rats (n=18) Pylorus and forestomach ligation operation-induced RE	Lonicerae Flos Extract	Oral (1회/day), 2 weeks	① gastric volume ② gastric acid and pepsin output ③ hexose ④ sialic acid ⑤ serume histamine	① decreased ② decreased ③ increased ④ increased ⑤ decreased

Table 4

Clinical Research about Gastroesophageal Reflux Disease

Author	Sample size	Treatment period	Intervention	Result
Case report
Kim43) (2021)	M/30 (n=1)	22 days	herbal decoction (Taeumin Cheongsimyeonja-tang), acupuncture (BL18, BL13, BL20, CV12, ST36, PC6, LR3)	GSRS improved from 4.8 to 2.6. Clinical symptoms of sore throat, cough, phlegm and bowel sound were improved.
Kim44) (2021)	F/69 (n=1)	13 days	herbal decoction (Jeonjeonggamiijin-tang Ga Cheongpi, Moryeobun, Baekjakyak), herbal extracts (Jakyakgamcho-tang, Opae-san), acupuncture, electroacupuncture (ST36-SP6)	RSI and EQ-5d scores improved, but VAS scores showed that only heartburn, acid reflux, and chest pain symptoms were relieved.
Jun45) (2020)	M/54 (n=1)	8 days	herbal decoction (Beewha-eum), herbal extracts (Banhasasim-Tang), acupuncture (Ex-HN05, LI04, LR03, SP04, ST36, SP06), electroacupuncture(ST36-ST37), moxibustion (CV12, CV04)	The severity of chest pain was decreased. The self-reported dyspepsia degree also decreased. KGSRS and GIS score was decreased. FD-QOL score was increased.
Na46) (2017)	M/34 (n=1)	12 days	herbal decoction (Soojeom-san plus Jeungmiyijin-tang), acupuncture (CV13(上脘), CV12(中脘), CV10(下脘), ST36(足三里), SP6(三陰交), SP04(公孫), PC6(內關), moxibustion (CV12, CV4), cupping (BL20, BL21)	Symptoms of GERD such as chest pain, heartburn, and acid regurgitation are almost disappeared. The patient don’t need to take the proton pump inhibitor therapy. There was significant increase of % bradygastria parameters in fed EGG. And significant increase of the power ratio was shown.
Lee47) (2017)	M/60 (n=1)	19 days	herbal decoction (Gyejibanhasaenggang-tang, Guibi-tang), herbal extracts (Banhasasim-Tang), acupuncture (LI4, LR3, ST 36, EX-HN5), moxibustion (CV12, CV4)	clinical symptoms were improved. VAS, GIS, and GSRS scores were improved.
Kim49) (2016)	F/51 (n=1)	26 days	herbal decoction (Anjoongsan-gami-bang, Samchulkunbi-tang-gami-bang, Banhahubak-tang-gami-bang), acupuncture (LI4, LR3, CV12, ST36, PC4, SP6, ST41), pharmacopuncture (Hwangnyeonhaedok-tang 0.4 cc ST9, ST10), moxibustion (CV12)	the patient’s food intake increased and Numeric rating scale (NRS) scores of heart burning pain and dysphagia were diminished.
Yoon48) (2016)	F/28 (n=1)	2012.4.10.~2012.8.9 (122 days) 2013.7.20.~2013.12.14 (148 days)	herbal decoction (pyeongyoe san-gami-bang), herbal extracts (Sojukgunbi-hwan), acupuncture (CV13, CV12, CV10, ST36), electroacupuncture(ST36), moxibustion (CV12)	All the patients’symptoms had disappeared, and the mucosa of the esophagus had returned to normal.
Kim50) (2011)	F/74 (n=1)	11 weeks	herbal decoction (Yeoldahanso-tang), acupuncture (Ganseunggyeok), medication (proton pump inhibitor, first 3 weeks)	Symptoms of GERD such as chest pain, heartburn, and acid regurgitation are almost disappeared. The patient don’t need to take the proton pump inhibitor therapy. There was significant increaseof % bradygastria parameters in fed EGG. And significant increase of the power ratio was shown.
Park51) (2006)	F/39 (n=1)	2 months	herbal decoction (Bokryungyeum-tang), Herbal Formulae (Banhasasim-tang, Hyangsayangyi-tang, Opae-san, Sojukgunbi-hwan), acupuncture (LI4, ST36), moxibustion (CV4, CV12)	Severe symptoms and lower quality of life which have not responded to more than 6 months’ western medical therapy (acid suppression) were improved.
Lee52) (2005)	F/78 (n=1)	57 days	herbal decoction (Daebowonjeon, Sameumjeon, Oeumjeon)	Clinical symptoms (nausea, vomitting) were improved. Hematologic findings and biochemistry findings got in normal range.
Baek53) (2004)	M/65 (n=1)	50 days	herbal decoction (Yanggyuksan, Yanggyuksanhwa-tang, Jaeumganghwa-tang plus Seongsimsan, Hwangnyeonsobi-hwan, Banhasasim-tang), acupuncture (CV12, ST25, LI4, LR3, SP36, PC6, SP4), moxibustion (CV12, CV8, CV4), cupping (Back-Shu Points, GV9), aromatherapy	clinical symptoms were improved.
Case series
Lee54) (2017)	① F/75 ② F/50 ③ F/53	2 weeks	herbal decoction (Ojeok-san plus Saengmaek-san), acupuncture (LI4, LR3, CV13, CV12, CV10, CV17, PC6, LI11, ST36, SP6)	Cough VAS decreased. LCQ-K increased.
Ha55) (2017)	n=12	4 weeks	herbal decoction (Lijin-tang-gamibang)	Clinical characteristics were improved (acid regurgitation and heartburn). Each symptom score of NDI-K, KGSRS, NRS, SQDQ, and PGIC showed significant advances.
Lim56) (2015)	① F/51 ② M/60	① 20 days ② 16 days	① herbal decoction (Soyangin Hyeongbangjihwang-tang), acupuncture (CV12, BL21, ST40, ST36, ST43, ST44, HT7, SP4, PC6), cupping (BL20, BL21, BL18, BL19), medication (4 days) ② herbal decoction (Soyangin Hyeongbangjihwang-tang), acupuncture (CV12, BL21,ST40, ST36, ST43, ST44)	A female patient’s symptoms such as dyspepsia, chest discomfort were almost cured. But they increased with patient’s emotional state repeatedly. A male patient’ symptoms such as abdominal pain, dyspepsia, nausea, heart burn were successfully disappeared.
Kim57) (2015)	① F/49 ② F/52 ③ F/44 ④ F/66	① 26 days ② 31 days ③ 15 days ④ 13 days	① herbal decoction (Insambaekhab-tang), Herbal Formulae (Opaesan plus Jakyakgamcho-tang-gagam-bang, SokPyeonAnGel, SPAG) ② herbal decoction (Pyeongyoesan-gagam), Herbal Formulae (Opaesan plus Jakyakgamcho-tang-gagam-bang, SokPyeonAnGel, SSPAG) ③ herbal decoction (Bojungikgi-tang, GwakHyang-JungGiSan), Herbal Formulae (Opaesan plus Jakyakgamcho-tang-gagam-bang, SokPyeonAnGel, SPAG), acupuncture, pharmacoacupuncture (junggihaham) ④herbal decoction (Danchisoyosan), Herbal Formulae (Opaesan plus Jakyakgamcho-tang-gagam-bang, SokPyeonAnGel, SPAG), acupuncture, pharmacoacupuncture (junggihaham)	GerdQ scores decreased.
Kim58) (2005)	① M/43 ② M/35 ③ F/29 ④ M/28 ⑤ M/28 ⑥ F/28 ⑦ F/36	3 months	herbal decoction (lijintang-gamibang), acupuncture (ST40, CV12, CV14, ST36, GB28, LR4, BL21, BL23)	The clinical progress (Ordinal Scales VI Grade and VAS) were improved.
Assessment scales study
Han59) (2015)	n=23			The study developed a standard tool for pattern identification of gastroesophageal reflux disease (PIGERD) for standardized diagnosis. Four pattern identifications [pattern/syndrome of liver qi invading the stomach (肝胃不和), spleen-stomach weakness (脾胃虛弱), spleen-stomach dampness-heat (脾胃濕熱), and stomach yin deficiency (胃陰不足)] and 49 symptoms were then selected.
Choi60) (2022)	n=50			The questionnaire showed that the reorganized standard tool had high reliability and moderate validity.(Cronbach alpha=0.834, intra class correlation coefficient of 0.907)
Comparative study
Baek61) (2019)	n=29	1 year	the GERD with globus senstion group (GS group) the GERD without globus senstion grou p (non-GSgroup)	The duration of the symptom in the GS group was significantly longer than that in the non-GS group. In HRV parameters, the non-GS group showed a significantly higher value of total power and high frequency than the GS group.

Table 5

Clinical Symptoms of Gastroesophageal Reflux Disease

Author (year)	case number	clinical symptoms
		heartburn	regurgitation	chest pain	abdominal pain	dysphagia	cough	globus	nausea
Kim43) (2021)	1	1			1		1	1
Kim44) (2021)	1	1			1			1	1
Jun45) (2020)	1	1			1
Na46) (2017)	1	1			1
Lee47) (2017)	1	1	1		1			1
Yoon48) (2016)	1				1			1
Kim49) (2016)	1	1	1		1	1		1
Kim50) (2011)	1	1	1	1	1
Park51) (2006)	1		1	1	1
Lee52) (2005)	1								1
Baek53) (2004)	1			1	1		1	1	1
Lee54) (2017)	3						3
Ha55) (2017)	12	7	9		4		3	4	4
Lim56) (2015)	2	1		2	1				1
Kim57) (2015)	4	4	4		2			1	2
Kim58) (2005)	7	7	7	7	7	6	6	7
Baek61) (2019)	29		20	5	9				3
total		26	44	17	33	7	14	18	13

Table 6

The Pattern Identification of Gastroesophageal Reflux Disease

Frequency (time)	Pattern identification
4	脾胃虛弱(脾氣虛, 氣虛, 脾氣虛), 氣鬱痰阻(肝氣鬱結, 中焦痰火, 食積痰)
3	脾胃濕熱(胃熱)
2	瘀血(血瘀)
1	胃陰虛, 肝胃不和, 少陽人身寒腹痛亡陰證, 少陽人身熱頭痛亡陰證, 太陰人燥熱證 (太陰人肝受熱裡熱病肺燥肝熱證), 少陰人太陰病痞滿證, 少陰人裡寒病

Table 7

List of Herbal Medication in Clinical Treatments of Study Case

Frequency (time)	Herb medication
4	半夏瀉心湯
2	芍藥甘草湯, 平胃散, 消積健脾丸, 二陳湯
1	太陰人淸心蓮子湯, 正傳加味二陳湯, 比和飮桂枝半夏生薑湯, 歸脾湯, 安中散, 蔘出健脾湯, 半夏厚朴湯茯苓飮, 香砂養胃湯大補元煎三陰煎, 五陰煎, 涼膈散, 凉膈散火湯滋陰降火湯合醒心散, 黃連消痞丸, 五積散合生脈散, 少陽人荊防地黃湯, 人參百合湯, 藿香正氣散, 丹梔消遙散, 熱多寒少湯, 手拈散合增味二陳湯

Table 8

List of Herbal Name

Frequency (time)	Herb name
22	甘草 (Glycyrrhizauralensis)
15	茯苓 (Poria cocas Wolf.)
14	白朮 (Atractylodes japonica Koidzumi)
13	生薑 (Zingiberofficinale)
12	陳皮 (CitrusunshiuMarkovich)
11	人蔘 (Panaxginseng)
9	半夏 (Pinelliaternate), 大棗(Zizyphusjujuba Mill)
8	白芍藥 (Paeoniajaponica)
6	厚朴1 (Machilusthunbergii), 當歸 (Angelica gigas Nakai), 砂仁 (Amomumxanthoides)
5	蒼朮 (Atractylodes japonica), 黃芩 (Scutellariabaicalensis), 地黃 (Rehmannia glutinosa (Gaertn.) Libosch.)
4	藿香(Agastacherugosa), 桂枝 (Cinnamomi Ramulus), 乾薑(Zingiber officinale), 神麯 (Massa Medicata Fermentata)
3	桔梗 (Platycodon grandiflorum A. De Candolle), 薄荷(Mentha canadensis L.), 梔子(Gardenia jasminoides Ellis), 麥門冬 (Liriope platyphylla), 木香 (Aucklandialappa Decaisne), 白芷 (Angelicae Dahuricae Radix), 山楂 (Crataeguspinnatifida Bunge), 麥芽 (Hordeum vulgare Linné), 山藥(Disocoreabatatas), 遠志 (Polygala tenuifolia), 酸棗仁 (Ziziphi Spinosae Semen), 枳實(Poncirustrifoliata Rafinesque), 五味子 (Schisandra chinensis)
2	連翹 (Forsythiae Frucus), 川芎 (Cnidiumofficinale), 香附子 (Cyperusrotundus L.), 枳殼 (poncirus trifoliata), 紫蘇葉 (Perilla frutescens Britton var. acuta Kudo), 黃連 (Coptis japonica), 蘿蔔子(Raphanus sativus L.), 葛根(Puerarialobata), 白豆蔲 (Amomum cadamomum), 知母 (Anemarrhena asphodeloides Bunge), 天門冬 (Asparagus cochinchinensis), 石菖浦 (Acorus gramineus), 龍眼肉 (Longanae Arillus)

Table 9

List of Acupoints in Clinical Treatments

Frequency (time)	Acupoints
11	足三里 (ST36)
8	中脘 (CV12)
5	合谷 (LI4) 太衝 (LR3) 內關 (PC6)
4	孔孫4 (SP4)
3	三陰交 (SP6) 上脘 (CV13) 下院 (CV10)
2	太陽 (EX-HN5) 中封 (LR4) 豊隆 (ST40) 胃兪 (BL21)
1	巨闕 (CV14) 人迎 (ST9) 水突 (ST10) 上巨虛 (ST37) 解谿 (ST41) 內庭 (ST44) 陷谷 (ST43) 勞宮 (PC8) 大陵 (PC7) 少府 (HT8) 行間 (LR2) 經渠 (LU8) 膻中(CV7) 曲池 (LI11) 維道 (GB28) 腎兪 (BL23) 脾兪 (BL20) 肝兪 (BL18) 肺兪 (BL13)

Table 10

Clinical Progress

Author (year)	Case number	Clinical symptoms
Author (year)	Case number	heartburn	regurgitation	chest pain	abdominal pain	dysphagia	cough	globus	nausea
Kim43) (2021)	1	GSRS5 →3	GSRS5 →3		GSRS6 →3		+ →−	++ →−	GSRS3 →2
Kim44) (2021)	1	VAS6.1 →2.6			VAS5.5 →2.1			VAS4.2 →3.4	VAS4.4 →2.2
Kim44) (2021)	1	RSI 27 →14, EQ-5d 0.553 →0.712
Jun45) (2020)	1	100% →65%		NRS8 →0	100% →65%
Jun45) (2020)	1	KGSRS 49 →35, GIS 16 →9, FD-QoL 20 →25
Na46) (2017)	1	VAS10 →0			VAS10 →1
Na46) (2017)	1				FSSG 39 →5
Lee47) (2017)	1	++ →+	+++ →+		++ →+			++ →+
Lee47) (2017)	1	VAS80 →35, GSRS (improved/unknown) GIS(improved/unknown)
Yoon48) (2016)	1				+++ →−			++ →−
Yoon48) (2016)	1	endoscopy, electrogastrography, enterotachography findings: normal
Kim49) (2016)	1	NRS10 →1	loss			NRS10 →7		loss
Kim50) (2011)	1	loss	loss	loss	unchanged
Kim50) (2011)	1	electrogastrography: normal
Park51) (2006)	1	+ →−	+ →−	+++ →±	++ →−
Lee52) (2005)	1								loss
Lee52) (2005)	1	Hematologic findings(HGB, HCT, MCV, MCH, MCHC) and biochemistry findings (Protein, total albumin, total bilirubin: normal
Baek53) (2004)	1			+++ →±	+++ →±		++ →+	++ →+	++ →−
Lee54) (2017)	①						Cough VAS 80 →20
Lee54) (2017)	①				LCQ-K 54 →84
	②						Cough VAS 90 →20
	②				LCQ-K 40 →94
	③						Cough VAS 60 →20
	③				LCQ-K 78→106
Ha55) (2017)	12	NDI-K 57.4±39.9 → 21.5±12.9 KGSRS 25.9±6.0 → 17.6±3.9 NRS 5.8±2.2 → 2.3±1.8 KPSS-10 18.75±3.2 → 16.0±4.0 QSQ 34.3±22.9 → 19.1±11.6 SQDQ 175.0±71.4 → 101.0±53.3 PGIC improved
Lim56) (2015)	①			improved	improved
	②	improved		improved					improved
Kim57) (2015)	①	improved
Kim57) (2015)	①				GerdQ 7 →4
	②	improved	unchanged		improved				improved
	②				GerdQ 8 →5
	③	unchanged	unchanged		improved				improved
	③				GerdQ 8 →6
	④		improved					improved
	④				GerdQ 5 →4
Kim58) (2005)	①	VAS10 →0	VAS10 →2	VAS10 →4	VAS10 →7	VAS10 →5		VAS10 →7
	②	VAS10 →3	VAS10 →2	VAS10 →8	VAS10 →6	VAS10 →7	VAS10 →8	VAS10 →5
	③	VAS10 →2	VAS10 →0	VAS10 →7	VAS10 →6	VAS10 →7	VAS10 →5	VAS10 →4
	④	VAS10 →3	VAS10 →2	VAS10 →6	VAS10 →8		VAS10 →2	VAS10 →8
	⑤	VAS10 →6	VAS10 →0	VAS10 →8	VAS10 →5	VAS10 →8	VAS10 →7	VAS10 →0
	⑥	VAS10 →3	VAS10 →1	VAS10 →3	VAS10 →3	VAS10 →5	VAS10 →4	VAS10 →3
	⑦	VAS10 →2	VAS10 →0	VAS10 →5	VAS10 →5	VAS10 →6	VAS10 →0	VAS10 →0

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