Efficacy and Safety of Ojeok-San Plus Saengmaek-San for Gastroesophageal Reflux-Induced Chronic Cough: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial.

Introduction: Gastroesophageal reflux-induced chronic cough (GERC) is one of the most common etiologies of chronic cough. Despite the growing prevalence and interest in GERC, no effective treatment is currently available. In our study, we used a combination of herbal medicines, Ojeok-san (OJS) plus Saengmaek-san (SMS), for the treatment of GERC. Methods: We conducted a pilot, randomized, placebo-controlled, parallel-arm, single-center clinical trial to assess the feasibility of our study protocol, as our study is the first herbal medicine trial for GERC. All enrolled participants were randomly assigned to either the intervention or placebo group in a 1:1 ratio and were administered trial drugs three times a day for 6 weeks, with an evaluation visit performed every 2 weeks for their efficacy and safety assessment until the follow-up visit (week 8). We evaluated the severity and frequency of cough, cough-specific quality of life, airway hypersensitivity, and reflux-related gastrointestinal symptoms, as well as pattern identification, to investigate the complex mechanisms of reflux cough syndrome. Results: A total of 30 participants were enrolled, and 25 completed the study at Kyung Hee University Korean Medicine Hospital from 26 December 2018 to 31 May 2021. OJS plus SMS significantly improved the cough diary score (CDS), cough visual analog scale, Korean version of the Leicester Cough Questionnaire, Hull Airway Reflux Questionnaire, and Gastrointestinal Symptom Rating Scale after the treatment compared to the baseline. Notably, OJS plus SMS showed significant efficacy in the daytime and total CDS compared with the placebo. Only one adverse event was observed during the trial, and no serious adverse events occurred. Additionally, we achieved successful results in feasibility outcomes by exceeding the ratio of 80%. Conclusion: We confirmed the feasibility of our trial design and demonstrated the potential of OJS plus SMS in relieving the severity of cough and GI symptoms in GERC patients with safe and successful feasibility results. We anticipate that our study results will be used as the basis for further large-scale, well-designed, confirmatory trials to evaluate the safety and efficacy of OJS plus SMS in GERC. Clinical Trial Registration: [https://cris.nih.go.kr], identifier WHO International Clinical Trials Registry Platform, Clinical Research Information Service [KCT0003115].

Efficacy and safety of Ojeok-san plus Saengmaek-san for gastroesophageal reflux-induced chronic cough: protocol for a pilot, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a major cause of chronic cough. GERD-induced chronic cough is difficult to diagnose because some patients do not complain of any gastrointestinal (GI) reflux symptoms. Although chronic cough due to GERD is highly prevalent, no effective treatment is currently available, especially for GERD-related cough without GI symptoms. Because the herbal medicines Ojeok-san and Saengmaek-san can effectively treat GERD and cough, we aim to evaluate the efficacy and safety of a combination of these components for relieving chronic cough due to GERD. METHODS/DESIGN: This is a study protocol of a randomized, double-blind, placebo-controlled, single-center pilot trial. After a 1-week run-in period, a total of 30 patients with GERD-induced chronic cough will be randomly allocated to an intervention group (n = 15) or a placebo group (n = 15). Participants will receive 5.76 g of Ojeok-san plus Saengmaek-san or a placebo three times per day for 6 weeks. The primary outcome measures, which are the frequency and severity of cough, will be recorded using a cough diary. The secondary outcome measures will include a cough visual analogue scale, the Leicester Cough Questionnaire (Korean version), the Gastrointestinal Symptom Rating Scale, the Hull Airway Reflux (hypersensitivity) Questionnaire, the Pattern Identification for Chronic Cough Questionnaire, the Pattern Identification for Gastroesophageal Reflux Disease, and safety testing. Adverse events will also be reported. DISCUSSION: This will be the first clinical trial to explore the use of herbal medicines for GERD-related chronic cough, including patients without GI reflux symptoms. This study will provide useful evidence regarding the efficacy and safety of Ojeok-san plus Saengmaek-san treatment. In addition, this trial will offer a scientific basis for the combination of herbal medicines. This study will also provide important data for conducting a larger-scale clinical trial on GERD-induced chronic cough. TRIAL REGISTRATION: This trial has been registered with Clinical Research Information Service (CRIS) of South Korea (http://cris.nih.go.kr; registration number KCT0003115). Registered August 28, 2018.

Ojeok-san, a traditional Korean herbal medicine attenuates airway inflammation and pulmonary fibrosis induced by repeated ovalbumin challenge.

ETHNOPHARMACOLOGICAL EVIDENCE: Ojeok-san, a traditional Korean herbal medicine, is widely used in China, Japan and Korea for treatment of the common cold, pain and fever. AIM OF THE STUDY: In this study, we investigated the protective effects of Ojeok-san aqueous extract (OJS) against pulmonary fibrosis using a chronic asthma murine model. METHODS: Mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed 1 weeks later by an airway challenge with OVA delivered three times a week for 4 weeks. OJS (50mg/kg or 100mg/kg) was also administered by oral gavage once a day for 4 weeks. RESULTS: OJS significantly reduced interleukin (IL)-4, IL-13, eotaxin, immunoglobulin E and the number of inflammatory cells in bronchoalveolar lavage fluid; in addition, it reduced inflammatory cell infiltration and mucus production in the respiratory tract. We found that OJS also attenuated the OVA-induced increase in vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß1 and Smad3 protein in lung tissue, as determined by Western analysis and immunohistochemistry. These inhibitory effects of OJS were accompanied by a reduction in pulmonary fibrosis, consistent with the histopathology of lung tissue stained with Masson's trichrome. CONCLUSION: Administration of OJS reduced the airway inflammation and pulmonary fibrosis, as well as the level of T helper type 2 cytokines and VEGF and TGF-ß1/Smad3 expressions in lung tissue. These results suggest that OJS might represent a useful new oral therapy for the treatment of chronic asthma.

Compositional Differences of Ojeok-san (Wuji-san) Decoctions Using Pressurized or Non-pressurized Methods for Variable Extraction Times.

This study compared Ojeok-san (Wuji-san in Chinese) decoctions produced using different extraction methods for variable times. Decoctions were extracted in pressurized or non-pressurized conditions for 60, 120, and 180 mins. We investigated the Ojeok-san extract yield, the total soluble solid content, the hydrogen ion concentration (pH), and the reference compound content. The extract yield and the total soluble solid content were higher in decoctions produced by non-pressurized extraction; both were proportional to the extraction time. The pH tended to decrease as the extraction time was increased in decoctions produced using both methods. After 60 and 180 mins, the levels of albiflorin, paeoniflorin, nodakenin, naringin, and neohesperidin were significantly higher in decoctions extracted using the non-pressurized method compared with those extracted using the pressurized method. After 120 mins, only cinnamaldehyde was extracted in a greater amount in pressurized decoctions compared with non-pressurized decoctions. The levels of paeoniflorin, ferulic acid, nodakenin, naringin, hesperidin, neohesperidin, and glycyrrhizin increased with time in non-pressurized decoctions. This study showed that the use of pressurized and non-pressurized extraction methods for different times affected the composition of Ojeoksan (Wuji-san) decoctions.