Rikkunshito, a Japanese Kampo Medicine, Ameliorates Decreased Feeding Behavior via Ghrelin and Serotonin 2B Receptor Signaling in a Novelty Stress Murine Model

Yamada, Chihiro; Saegusa, Yayoi; Nakagawa, Koji; Ohnishi, Shunsuke; Muto, Shuichi; Nahata, Miwa; Sadakane, Chiharu; Hattori, Tomohisa; Sakamoto, Naoya; Takeda, Hiroshi

doi:10.1155/2013/792940

Cited by 25 publications

(33 citation statements)

References 35 publications

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“…The ameliorative effect of RKT on hypophagia in young mice has been previously reported in several studies1823. Therefore, we investigated the distribution of RKT components in young animals in the present study.…”

Section: Resultsmentioning

confidence: 72%

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

Mogami

Sadakane

Nahata

et al. 2016

Sci Rep

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Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities.

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Section: Resultsmentioning

confidence: 72%

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

Mogami

Sadakane

Nahata

et al. 2016

Sci Rep

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“…Isoliquiritigenin had a spasmolytic effect on uterine contraction in a concentration‐dependent fashion in vitro and reduced the acetic acid‐induced writhing response and hot‐plate test in vivo, of which the mechanism involved Ca 2+ channels, NOS, and COX (Shi et al, ). Likewise, it suggested that ISL, isolated from RKT, could improve the decrease in food intake after exposure to novelty stress by antagonizing 5‐HT2B receptor (Yamada et al, ).…”

Section: Pharmacological Effectsmentioning

confidence: 99%

A Review: The Pharmacology of Isoliquiritigenin

Peng

et al. 2015

Phytotherapy Research

200

139

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Isoliquiritigenin (ISL) is one of the bioactive ingredients isolated from the roots of plants belonging to licorice, including Glycyrrhiza uralensis, Mongolian glycyrrhiza, Glycyrrhiza glabra, and so forth. Liquiritigenin is available in common foods and alternative medicine, and its derivative-ISL is applied into food additives and disease treatment like cancer therapy, antibiotic therapy, and so on. This review aims at providing a comprehensive summary of the pharmacological activities of ISL. The information published between 1972 and 2014 from a number of reliable sources including PubMed, ScienceDirect, Springer, and Wiley-Blackwell. The practical application of ISL on the various disease prevention and treatments may stem from its numerous pharmacological properties such as antiinflammatory, anti-microbial, anti-oxidative, anticancer activities, immunoregulatory, hepatoprotective, and cardioprotective effects. However, further studies are needed to verify the target-organ toxicity or side effects investigation.

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“…A previous study has shown that a 5‐HT 2B receptor antagonist reversed stress‐induced colonic hypersensitivity in a rat model of brain‐gut axis dysfunction . Another study reported that 5‐HT 2B receptor antagonists suppressed a decrease in food intake in a rat novelty stress model . However, there have not been any studies on the relationship between 5‐HT 2B receptors and stress‐induced impairment of GA.…”

Section: Introductionmentioning

confidence: 99%

Impairment of gastric accommodation induced by water‐avoidance stress is mediated by 5‐HT_2B receptors

Miwa

Koseki

Oshima

et al. 2016

Neurogastroenterology Motil

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Key Points• Psychological stress causes impaired gastric accommodation (GA), which is associated with early satiety in patients with functional dyspepsia. However, the mechanism by which stress inhibits GA remains unknown.• The aim of this study was to investigate the influence of stress on GA, and the involvement of 5-HT 2B receptors in the impairment of GA using an animal model.• After subjection to water-avoidance stress, GA in conscious guinea pigs was evaluated by measuring the intrabag pressure following administration of a liquid meal.• The present study revealed that GA was inhibited by stress, and that this inhibition was mediated by an increased responsiveness of 5-HT 2B receptors in the gastric fundus. AbstractBackground Psychological stress has been shown to impair gastric accommodation (GA), but its mechanism has not been elucidated. This study was conducted to clarify the role of 5-HT 2B receptors in a guinea pig model of stress-induced impairment of GA. Methods Gastric accommodation was evaluated by measuring the intrabag pressure in the proximal stomach after administration of a liquid meal. The guinea pigs were subjected to water-avoidance stress. The role of 5-HT 2B receptors in impairment of GA was investigated by administering a 5-HT 2B receptor agonist (BW723C86) or antagonist (SB215505), the traditional Japanese medicine rikkunshito (RKT), a muscarinic M 3 receptor antagonist (1,1-dimethyl-4-diphenylacetoxypiperidium iodide [4-DAMP]), or a nitric oxide synthase inhibitor (N x -nitro-L-arginine [L-NNA]). Key Results In normal animals, liquid meal-induced GA was inhibited by BW723C86, but was not affected by SB215505. The inhibition of GA by BW723C86 was reversed by co-administration of 4-DAMP. Compared to normal animals, GA in stressed animals was significantly inhibited. SB215505 and RKT significantly suppressed stress-induced impairment of GA. After meal administration, the level of cyclic guanosine monophosphate in gastric fundus tissue increased by approximately twofold in normal animals, but did not change in stressed animals. The inhibition of GA by L-NNA was suppressed by SB215505 or RKT. At a dose that did not affect GA in normal animals, BW723C86 exacerbated the impairment of GA in stressed animals. Conclusions and Inferences Stress-induced impairment of GA may be mediated by an increased responsiveness of 5-HT 2B receptors, and activation of the 5-HT 2B receptor signaling pathway may have an inhibitory effect on nitric oxide function.

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Rikkunshito, a Japanese Kampo Medicine, Ameliorates Decreased Feeding Behavior via Ghrelin and Serotonin 2B Receptor Signaling in a Novelty Stress Murine Model

Cited by 25 publications

References 35 publications

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

A Review: The Pharmacology of Isoliquiritigenin

Impairment of gastric accommodation induced by water‐avoidance stress is mediated by 5‐HT_2B receptors

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Rikkunshito, a Japanese Kampo Medicine, Ameliorates Decreased Feeding Behavior via Ghrelin and Serotonin 2B Receptor Signaling in a Novelty Stress Murine Model

Cited by 25 publications

References 35 publications

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

A Review: The Pharmacology of Isoliquiritigenin

Impairment of gastric accommodation induced by water‐avoidance stress is mediated by 5‐HT2B receptors

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Impairment of gastric accommodation induced by water‐avoidance stress is mediated by 5‐HT_2B receptors