Clinical efficacy of Yukgunja-tang combined with a proton pump inhibitor for refractory gastroesophageal reflux disease: study protocol for randomized, double-blind, double-dummy clinical trial.

BACKGROUND: Yukgunja-tang (YGJ) is an herbal prescription used to treat the symptoms of gastroesophageal reflux disease (GERD). Although many preclinical and clinical studies on YGJ have been conducted on GERD, there is a lack of evidence from blinded studies to exclude placebo effects. Therefore, this protocol proposes a clinical trial that is single-centered, randomized, double-blinded, double-dummy to objectively evaluate the efficacy and safety of co-administered YGJ and rabeprazole (RPZ) in patients with GERD previously treated with proton pump inhibitors (PPIs) and still experiencing symptoms. METHODS: A total of 86 participants with refractory GERD (rGERD) will be randomized in a 1:1 ratio to the treatment [YGJ and RPZ (10 mg/d)] and control groups [double-dose RPZ (20 mg/d)] for 4 weeks of treatment (weeks 0-4) followed by 4 weeks of follow-up (weeks 4-8). The Frequency Scale for the Symptoms of GERD will be analyzed for the primary endpoint. Reflux Disease Questionnaire, Reflux Symptom Score, GERD-Health Related Quality of Life, Overall Treatment Evaluation, Spleen Qi Deficiency Questionnaire, Damum Questionnaire, and dyspepsia Visual Analogue Scale will be used to evaluate treatment effects on GERD related symptoms and quality of life and to compare treatment effects by subgroups. Safety tests will be analyzed by investigating adverse events. DISCUSSION: This clinical trial will be the first rigorous double-blind, double-dummy, placebo-controlled study to precisely evaluate the efficacy and safety of the combination of YGJ and PPIs in the treatment of rGERD. The results of this study will provide a reliable clinical basis for selecting botanical drug treatments for patients with rGERD. TRIAL REGISTRATION: Clinical Research Information Service (registration number: KCT0008600, July 13, 2023, https://cris.nih.go.kr ).

Herbal Medicine Yukgunja-Tang for Functional Dyspepsia: A Protocol for a Randomized, Controlled, Multicenter Clinical Trial.

The herbal medicine Yukgunja-tang has been widely used for the treatment of functional dyspepsia (FD) in the clinical setting of East Asian traditional medicine. This paper presents a protocol for a randomized, assessor-blind, controlled, multicenter, three-arm parallel clinical trial comparing the effectiveness, safety, and cost-effectiveness of Yukgunja-tang with Pyeongwi-san and usual care. A total of 140 participants with Rome IV-diagnosed FD will be randomly assigned to either the Yukgunja-tang (n = 56), Pyeongwi-san (n = 56), or usual care (n = 28) groups. All participants will be educated on dietary guidelines for FD patients. Participants in the Yukgunja-tang and Pyeongwi-san groups will take investigational products for 6 weeks. All participants will be assessed for clinical parameters at weeks 0, 3, 6, 9, and 24. The primary outcome will be measured on the total dyspepsia symptom scale, and the secondary outcome will include the single dyspepsia symptom scale, overall treatment effect, the visual analog scale for dyspepsia, FD-related quality of life, hospital anxiety and depression scale, EuroQol-5 dimension, pattern identification, and serum levels of acyl-ghrelin and deacyl-ghrelin. Adverse events and laboratory tests will be monitored for safety assessment. The results will provide evidence of the effectiveness, safety, and cost-effectiveness of Yukgunja-tang in the treatment of FD.

Clinical Observation of Effects of Modified Xiangsha Liujunzi Tang Application on Adverse Reaction of Moderately/Highly Emetogenic Chemotherapy for Gastrointestinal Tumors / 中国实验方剂学杂志

Objective:To investigate the effects of external application of modified Xiangsha Liujunzi Tang in improving gastrointestinal reaction，immune function， and quality of life in patients with gastrointestinal tumors after moderately/highly emetogenic chemotherapy. Method:A total of 140 inpatients （from January 2018 to May 2021） with gastrointestinal malignancies diagnosed by the Oncology Department of Integrated Traditional Chinese and Western Medicine of China-Japan Friendship Hospital and treated with moderately/highly emetogenic chemotherapy were randomly divided into an experimental group （<italic>n</italic>=70） and a control group （<italic>n</italic>=70） according to the Good Clinical Practice （GCP）. Participants were given routine antiemetic treatment once 20 minutes before chemotherapy （tropisetron 5 mg + dexamethasone 5 mg or methylprednisolone 40 mg）. On this basis， the patients in the experimental group were treated with external application of modified Xiangsha Liujunzi Tang for 1 week on the second day after chemotherapy （the selected points were Zhongwan， Neiguan and Zusanli， 6 hours a day， and the application was changed every day）， and the patients in the control group were applied with comfort patch at the same time. The gastrointestinal reaction grade， subset concentration of lymphocytes， and Karnofsky score in two groups before and one week after chemotherapy were recorded， and all data were analyzed by SPSS 19.0 statistical software. Result:The grades of chemotherapy-related gastrointestinal reaction in two groups after treatment decreased as compared with that before treatment （<italic>P</italic><0.05）. The experimental group was superior to the control group after treatment in terms of grade decrease （<italic>P</italic><0.05）. The total response rate of the experimental group was 81.43% （57/70）， higher than 62.86% （44/70） in the control group （<italic>χ</italic>²=9.73， <italic>P</italic><0.05）. Stratified analysis was performed on the experimental group. Compared with the conditions before treatment， the grade of gastrointestinal reaction in patients with esophageal cancer and colorectal cancer of the experimental group decreased after treatment （<italic>P</italic><0.05）， and that in patients of different genders decreased after treatment （<italic>P</italic><0.05）. The results of immune function showed that there was no significant difference in the concentrations of CD3⁺， CD4⁺， CD8⁺， and NK cell subsets of the control group before and after treatment， while the concentrations of CD3⁺， CD4⁺， and NK cell subsets of the experimental group were higher than those before treatment and even superior to those in the control group （<italic>P</italic><0.05）. The Karnofsky score of quality of life in the experimental group was higher than that in the control group， with quality of life improved （<italic>P</italic><0.05）. Conclusion:External application of modified Xiangsha Liujunzi can improve the gastrointestinal reaction，immune function， and quality of life of patients with gastrointestinal tumors after moderately/highly emetogenic chemotherapy.

Liujunzi Tang, a famous traditional Chinese medicine, ameliorates cigarette smoke-induced mouse model of COPD.

ETHNOPHARMACOLOGICAL RELEVANCE: Liujunzi Tang is a traditional herbal medicine widely used in East Asia and clinically applied to treat Phlegm-Heat Syndrome. The purpose of the present study was to investigate the protective effects of Liujunzi Tang on cigarette smoke-induced (CS) mouse model of chronic obstructive pulmonary disease (COPD) and explore its potential molecular mechanism. MATERIALS AND METHODS: The mice received 1h of cigarette smoke for 8 weeks. The serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA) kits. Superoxide dismutase (SOD) and malondialdehyde (MDA) were tested by biochemical methods. Histopathological alteration was observed by hematoxylin-eosin (H&E) staining. Additionally, the expressions of nuclear transcription factor-κB (NF-κBp65) and (inhibitor of NF-κB)IκB-α were determined by western blot and immunohistochemistry analysis. RESULTS: Liujunzi Tang enhanced the activities of antioxidant enzymes and attenuated the levels of lipid oxidative production, meanwhile significantly inhibited the generations of inflammatory cytokines by inhibiting the phosphorylation of IκB-α and NF-κB. CONCLUSION: Our findings indicated that Liujunzi Tang exhibited the protective effect on cigarette smoke-induced COPD mice by anti-inflammatory and anti-oxidative properties through the inhibition of NF-κB activation.