Background: Yeokwisan, a standardized herbal formula, has exhibited clinical benefit for patients suffering from refractory functional dyspepsia (FD) in Korea since 2016. However, data about the mechanism of action of this formula are yet not available.Aim of the study: To evaluate and explore the effects of Yeokwisan on gastric emptying, a major symptom of functional dyspepsia, and its underlying mechanisms of action using a mouse model.Materials and methods: BALB/C mice were pretreated with Yeokwisan (100, 200, and 400 mg/kg, po) or mosapride (3 mg/kg, po) for 5 days and then treated with loperamide (10 mg/kg, ip) after 20 h of fasting. A solution of 0.05% phenol red (500 μL) or diet of 5% charcoal (200 μL) was orally administered, followed by assessment of gastric emptying or intestinal transit. Plasma acyl-ghrelin (ELISA), C-kit (immunofluorescence and western blotting), nNOS (western blotting) and gastric contraction- and ghrelin-related gene/protein expression levels were examined in stomach and small intestine tissues.Results: Loperamide injection substantially delayed gastric emptying, while Yeokwisan pretreatment (especially 200 and 400 mg/kg Yeokwisan) significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of phenol red retained in the stomach (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The levels of plasma acyl-ghrelin and expression of gastric ghrelin-related genes, such as growth hormone secretagogue receptor (GHSR), ghrelin-O-acyltransferase (GOAT), adrenergic receptor β1 (ADRB1) and somatostatin receptor (SSTR), were significantly normalized (p < 0.05 or 0.01) by Yeokwisan (400 mg/kg). Yeokwisan (400 mg/kg) significantly tempered the loperamide-induced alterations in the c-kit and nNOS levels (p < 0.01) as well as the expression of contraction- and ghrelin-related genes, such as 5-HT4 receptor (5-HT4R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK), in the stomach, but not in the small intestine.Conclusion: The present results showed the clinical relevance of Yeokwisan, in treating FD, especially in promoting gastric emptying but not small intestinal transit. The main mechanisms corresponding to these effects may involve the modulation of the ghrelin pathway and activation of interstitial cells of Cajal in stomach tissue.

The gastrointestinal (GI) tract has an intriguing and critical role beyond digestion in both modern and complementary and alternative medicine (CAM), as demonstrated by its link with the immune system. In this review, we attempted to explore the interrelationships between increased GI permeability and phlegm, an important pathological factor in CAM, syndrome, and therapeutic herbs for two disorders. The leaky gut and phlegm syndromes look considerably similar with respect to related symptoms, diseases, and suitable herbal treatment agents, including phytochemicals even though limitations to compare exist. Phlegm may be spread throughout the body along with other pathogens via the disruption of the GI barrier to cause several diseases sharing some parts of symptoms, diseases, and mechanisms with leaky gut syndrome. Both syndromes are related to inflammation and gut microbiota compositions. Well-designed future research should be conducted to verify the interrelationships for evidence based integrative medicine to contribute to the promotion of public health. In addition, systems biology approaches should be adopted to explore the complex synergistic effects of herbal medicine and phytochemicals on conditions associated with phlegm and leaky gut syndromes.

Introduction. The pathophysiology of functional dyspepsia (FD) remains uncertain, but the interstitial cells of Cajal (ICCs), pacemakers that regulate gastrointestinal motility, are garnering attention as key modulators and therapeutic targets in FD. This review comprehensively discusses the involvement of ICCs in the pharmacologic actions of FD and as therapeutic targets for herbal products for FD. Methods. A search of the literature was performed using PubMed by pairing “interstitial cells of Cajal” with “medicinal plant, herbal medicine, phytotherapy, flavonoids, or traditional Chinese medicine (TCM).” Results. From the 55 articles screened in the initial survey, 34 articles met our study criteria. The search results showed that herbal products can directly depolarize ICCs to generate pacemaker potentials and increase the expression of c-kit and stem cell factors, helping to repair ICCs. Under certain pathological conditions, medicinal plants also protect ICCs from oxidative stress and/or inflammation-induced impairment. Two representative herbal decoctions (Banhasasim-tang, 半夏泻心汤, and Yukgunja-tang, 六君子汤) have been shown to modulate ICC functions by both clinical and preclinical data. Conclusion. This review strongly indicates the potential of herbal products to target ICCs and suggests that further ICC-based studies would be promising for the development of FD treatment agents.

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.