Rikkunshito and 5-HT2C receptor antagonist improve cisplatin-induced anorexia via hypothalamic ghrelin interaction

Yakabi, Koji; Kurosawa, Susumu; Tamai, Mitsuo; Yuzurihara, Mitsutoshi; Nahata, Miwa; Ohno, Shino; Ro, Shoki; Kato, Shingo; Aoyama, Toru; Sakurada, Tomoya; Takabayashi, Hidehiko; Hattori, Tomohisa

doi:10.1016/j.regpep.2010.02.003

Cited by 63 publications

(43 citation statements)

References 42 publications

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“…To clarify whether a decrease in peripheral ghrelin levels participated in the appetite loss caused by the novelty stress, we used exogenous ghrelin and RKT, a drug that enhances ghrelin secretion in rodents (12,47,51) and humans (34). Intravenous administration of ghrelin inhibited the reduction in food intake caused by the novelty stress, and administering the GHS-R antagonist reversed the decrease in food intake compared with mice exposed to the novelty stress.…”

Section: Discussionmentioning

confidence: 99%

Decreased plasma ghrelin contributes to anorexia following novelty stress

Saegusa

Takeda

Muto

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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100

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We hypothesized that anorexia induced by novelty stress caused by exposure to a novel environment may be due to activation of corticotropin-releasing factor (CRF) and subsequently mediated by decreasing peripheral ghrelin concentration via serotonin (5-HT) and melanocortin-4 receptors (MC4R). Each mouse was transferred from group-housed cages to individual cages to establish the novelty stress. We observed the effect of changes in feeding behavior in a novel environment using the method of transferring group-housed mice to individual cages. We investigated the effect of an intracerebroventricular injection of antagonists/agonists of CRF1/2 receptors (CRF1/2Rs), 5-HT(1B)/(2C) receptors (5-HT(1B)/(2C)R), and MC4R to clarify the role of each receptor on the decrease in food intake. Plasma ghrelin levels were also measured. The novelty stress caused a reduction in food intake that was abolished by administering a CRF1R antagonist. Three hours after the novelty stress, appetite reduction was associated with reduced levels of neuropeptide Y/agouti-related peptide mRNA, increased levels of proopiomelanocortin mRNA in the hypothalamus, and a decrease in plasma ghrelin level. Administering a CRF1R antagonist, a 5-HT(1B)/(2C)R antagonist, an MC4R antagonist, exogenous ghrelin, and an enhancer of ghrelin secretion, rikkunshito, resolved the reduction in food intake 3 h after the novelty stress by enhancing circulating ghrelin concentrations. We showed that anorexia during a novelty stress is a process in which CRF1R is activated at the early stage of appetite loss and is subsequently activated by a 5-HT(1B)/(2C)R and MC4R stimulus, leading to decreased peripheral ghrelin concentrations.

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Section: Discussionmentioning

confidence: 99%

Decreased plasma ghrelin contributes to anorexia following novelty stress

Saegusa

Takeda

Muto

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

100

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“…Initially, we believed that the role of Rikkunshito in promoting gastric motility may be mediated by ghrelin because Rikkunshito elevates the low plasma ghrelin levels that are induced by cisplatin (40). Some subsequent studies (41)(42)(43) revealed that the pharmacological actions of Rikkunshito in promoting gastric motility may be associated with ghrelin. Therefore, our results corroborate the evidence obtained by previous studies showing that Rikkunshito has an effect on gastric motility.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Rikkunshito, a Traditional Japanese Medicine (Kampo), in Treating Functional Dyspepsia

et al. 2010

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Background Rikkunshito, a traditional Japanese (Kampo) medicine, is widely prescribed as an oral preparation for the treatment of functional dyspepsia (FD). In our previous study, we reported that extracorporeal ultrasonography (US) is a useful technique for the assessment of the gastric accommodation reflex (AR) and duodenogastric motility. In this study, we examined the effects of Rikkunshito on the gastroduodenal function in patients with FD. Methods Sixteen FD patients (median age, 45 y) underwent US, before and after 14 days of treatment with Rikkunshito (7.5 g b.d.). For assessment of the AR, a cross-sectional area of the proximal stomach was measured after incremental ingestion of a liquid meal up to 400-mL. The expansion rate was used as the parameter to determine the AR. Then, the gastric emptying rate (GER), motility index (MI), and reflux index (RI) were evaluated using previously reported methods. Results Although no significant changes were observed in the total score of the Gastrointestinal Symptom Rating Scale (GSRS), the scores of 3 of the 15 symptoms of GSRS decreased significantly after treatment with Rikkunshito. The expansion rate of the proximal stomach was significantly greater after treatment with Rikkunshito than before the treatment. Although the GER and MI increased significantly, no significant differences in the RI were observed after treatment with Rikkunshito. Conclusion These observations suggested that Rikkunshito may be beneficial for the treatment of FD patients with impaired AR and gastric motility. These results also suggested that Rikkunshito has a therapeutic potential for FD and GERD.

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“…Yakabi and colleagues demonstrated that hypothalamic ghrelin secretion was markedly reduced 24 and 48 h after cisplatin treatment in cisplatin-treated rats compared to saline-treated rats, though their plasma ghrelin levels did not differ [102,103]. In this study, it was found that the plasma acylated ghrelin level returned to the normal level within 24 h after a single administration of cisplatin, though the decreased food intake lasted for more than 48 h. They also demonstrated that i.c.v administration of ghrelin reversed the decreased in food intake in cisplatin-treated anorexic rats [102].…”

Section: Cisplatin-induced Anorexiamentioning

confidence: 99%

Anorexia in human and experimental animal models: physiological aspects related to neuropeptides

Yoshimura

Uezono²,

Ueta

2015

J Physiol Sci

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Anorexia, a loss of appetite for food, can be caused by various physiological and pathophysiological conditions. In this review, firstly, clinical aspects of anorexia nervosa are summarized in brief. Secondly, hypothalamic neuropeptides responsible for feeding regulation in each hypothalamic nucleus are discussed. Finally, three different types of anorexigenic animal models; dehydration-induced anorexia, cisplatin-induced anorexia and cancer anorexia-cachexia, are introduced. In conclusion, hypothalamic neuropeptides may give us novel insight to understand and find effective therapeutics strategy essential for various kinds of anorexia.

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Rikkunshito and 5-HT2C receptor antagonist improve cisplatin-induced anorexia via hypothalamic ghrelin interaction

Cited by 63 publications

References 42 publications

Decreased plasma ghrelin contributes to anorexia following novelty stress

Decreased plasma ghrelin contributes to anorexia following novelty stress

Efficacy of Rikkunshito, a Traditional Japanese Medicine (Kampo), in Treating Functional Dyspepsia

Anorexia in human and experimental animal models: physiological aspects related to neuropeptides

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