Kampo treatment for functional dyspepsia: focusing on rikkunshito “1st International Symposium on Kampo Medicine”

To the editor, The title of this gastrointestinal session is “Kampo treatment for functional dyspepsia: Focusing on rikkunshito,” and the discussion will focus on rikkunshito. Rikkunshito is very famous as a Kampo formula that improves gastrointestinal dysfunction. In Japan, not only Kampo doctors but also doctors who practice western medicine frequently use it in daily clinical practice. Rikkunshito is one of the Kampo formulas with the most fully elucidated mechanism of action, and research on rikkunshito related to the appetite-promoting hormone ghrelin is actively discussed at international conferences every year. Furthermore, in clinical practice, rikkunshito is not just an alternative medicine drug, but the subject of an international consensus clinical guideline for the upcoming revision of the Rome criteria dealing with the treatment of functional gastrointestinal disorders (FGIDs). In this way, rikkunshito has become remarkably popular internationally in recent years. Therefore, the purpose of this symposium is to give practitioners and researchers an updated understanding of rikkunshito and to suggest the best treatment for functional dyspepsia (FD). In this symposium, the current and future state of Kampo treatment of FD centered on rikkunshito will be explained and discussed from four points of view: clinical, basic, international, and evidencebased medicine from global authorities in each field. The first presentation is “Treatment strategies for functional dyspepsia in Kampo medicine.” In Kampo treatment for FD, it is important to find out if there is epigastric pain, as in western medicine. For postprandial distress syndrome without epigastric pain, rikkunshito and hangeshashinto are the main formulas clinically. Novices may first use rikkunshito according to the disease name. Secondly, if you have some knowledge about Kampo medicine, differentiating between excess and deficiency patterns in patients increases treatment efficiency. However, when the patient’s constitution is medium and the judgment is difficult, the chief complaints should be noted as the basis for selection of the prescription. Rikkunshito should be chosen for the chief complaint of loss of appetite, and hangeshashinto for that of epigastric discomfort. Furthermore, it may be better to consider the patient’s age. In general, rikkunshito is often adopted for treatment in the elderly because they tend to present the deficiency pattern. As other clinical differential formulas, hangekobokuto is frequently used for stress-induced FD accompanied by obstructive discomfort in the throat and chest, and anxiety and depression. The prescription used for the treatment of epigastric pain syndrome (EPS) differs depending on whether the pain is spastic or non-spastic. Saikokeishito is the first-line drug for treating EPS with spastic pain, while anchusan is prescribed for EPS with non-spastic pain. The second presentation is “Current knowledge about the pharmacological and molecular basis of rikkunshito’s action.” Although rikkunshito is widely used for the treatment of upper gastrointestinal symptoms, the molecular mechanisms were poorly understood. In 2008, we reported that rikkunshito is able to stimulate ghrelin secretion by antagonizing serotonin 2b/2c receptors. Later, we disclosed another interesting finding that rikkunshito extended healthy lifespan in mice by activating hypothalamic sirtuin 1 activity, which depends on the ghrelin system. Ghrelin is a peptide hormone discovered by Kojima et al. in 1999 as an endogenous ligand of the growth hormone secretagogue receptor, but shortly thereafter, it became evident that ghrelin has a much wider range of functions: it regulates food intake, adiposity, and glucose metabolism. It also stimulates gut motility and gastricacid secretion. More recent evidence strongly suggests that ghrelin acts as a “survival hormone” protecting the body from extreme nutritional and psychological stresses. Therefore, rikkunshito may enhance the selfdefending systems by activating ghrelin signaling, suggesting that it may be efficacious in the treatment of not only gastrointestinal dysfunctions but also a variety of pathologies including wasting diseases and neuropsychiatric disorders. Here, I will review current knowledge about the pharmacological and molecular basis of rikkunshito’s pleiotropic action. The third presentation is “International position of rikkunshito in the treatment of functional dyspepsia.” The Rome criteria, the international consensus clinical guideline for FGIDs, were revised in 2016 and Received: 20 May 2022 Revised: 12 July 2022 Accepted: 13 July 2022