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Review
. 2021 Dec 9:8:761631.
doi: 10.3389/fnut.2021.761631. eCollection 2021.

Ghrelin Enhancer, the Latest Evidence of Rikkunshito

Chihiro Yamada  1 , Tomohisa Hattori  1 , Shunsuke Ohnishi  2 , Hiroshi Takeda  3   4
Affiliations
Review

Ghrelin Enhancer, the Latest Evidence of Rikkunshito

Chihiro Yamada et al. Front Nutr. .

Abstract

Rikkunshito is a Japanese herbal medicine (Kampo) that has been attracting attention and researched by many researchers not only in Japan but also worldwide. There are 214 rikkunshito articles that can be searched on PubMed by August 2021. The reason why rikkunshito has attracted so much attention is due to an epoch-making report (Gastroenterology, 2008) discovered that rikkunshito promotes the secretion of the orexigenic peptide ghrelin. Since then, many researchers have discovered that rikkunshito has a direct effect on the ghrelin receptor, GHS-R1a, and an effect of enhancing the ghrelin signal to the brain. Additionally, a lot of evidence that rikkunshito is expected to be effective for various gastrointestinal diseases have also been demonstrated. Numerous basic and clinical studies have suggested that rikkunshito affects (i) various discomforts caused by anticancer drugs, gastroesophageal reflux disease, functional dyspepsia, (ii) various stress-induced anorexia, (iii) hypophagia in the elderly, and (iv) healthy lifespan. In this review, as one who discovered the ghrelin enhancer effect of rikkunshito, we will review the research of rikkunshito so far and report on the latest research results.

Keywords: GHS-R; Kampo; aging; anorexia; ghrelin; rikkunshito; stress.

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Conflict of interest statement

CY and TH are employees of Tsumura & Co. and get a salary from it. SO and HT receive research funds from Tsumura & Co. The authors declare that this study received funding from Tsumura & Co. The funder had the following involvement with the study: the decision to submit it for publication.

Figures

Figure 1
Figure 1
Summary of the mechanism of action of rikkunshito as a ghrelin enhancer. Ghrelin is produced from X/A-like cells near the gastric mucosa, and the ghrelin receptors at the ends of the vagus nerve in the surrounding tissues are stimulated. Most of it migrates to blood vessels and is carried to the brain. Serotonin, adrenaline, and CRF negatively regulate ghrelin secretion in the periphery. Rikkunshito suppresses the decrease in ghrelin that occurs in diseases by antagonistically acting on these factors with receptors in the periphery or central nervous system. Furthermore, rikkunshito enhances the binding of ghrelin to the ghrelin receptor and also acts on the ghrelin signal transduction system itself to enhance the ghrelin signal.
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