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Inashiki, Japan

Hattori T.,Tsumura and Co.
International Journal of Peptides | Year: 2010

Rikkunshito is a popular Japanese traditional medicine that is prescribed in Japan to treat various gastrointestinal tract disorders. In a double-blind controlled study, rikkunshito significantly ameliorated dysmotility-like dyspepsia and brought about a generalized improvement in upper gastric symptoms such as nausea and anorexia when compared with a control group. Several studies in rats have shown enhanced gastric emptying and a protective effect on gastric mucosa injury with rikkunshito administration. In addition, rikkunshito in combination with an anti-emetic drug is effective against anorexia and vomiting that occur as adverse reactions to chemotherapy in patients with advanced breast cancer. However, the mechanism by which rikkunshito alleviates gastrointestinal disorders induced by anticancer agents remains unclear. It has recently been shown that rikkunshito ameliorates cisplatin-induced anorexia by mediating an increase in the circulating ghrelin concentration. Moreover, Fujitsuka et al. found that decreased contractions of the antrum and duodenum in rats treated with a selective serotonin reuptake inhibitor were reversed by rikkunshito via enhancement of the circulating ghrelin concentration. These findings show that rikkunshito may be useful for treatment of anorexia and may provide a new strategy for improvement of upper gastrointestinal dysfunction. © 2010 Tomohisa Hattori.

Hattori T.,Tsumura and Co. | Yakabi K.,Saitama University | Takeda H.,Hokkaido University
Vitamins and Hormones | Year: 2013

Cisplatin, a formidable anticancer treatment, is used for several varieties of cancer. There are, however, many cases in which treatment must be abandoned due to a decrease in the patient's quality of life from loss of appetite associated with vomiting and nausea. There is a moderate degree of improvement in prevention of cisplatin-induced nausea and vomiting when serotonin (5-HT) 3 receptor antagonists, neurokinin 1 receptor antagonists, and steroids-either alone or in combination-are administered. The mechanism of action for anorexia, which continues during or after treatment, is, however, still unclear. This anorexia is, similar to the onset of vomiting and nausea, caused by the action of large amounts of 5-HT released as a result of cisplatin administration on tissue 5-HT receptors. Among the 5-HT receptors, the activation of 5-HT2b and 5-HT2c receptors, in particular, seems to play a major role in cisplatin-induced anorexia. Following activation of these two receptors, there is reduced gastric and hypothalamic secretion of the appetite-stimulating hormone ghrelin. There is ample evidence of the usefulness of exogenous ghrelin, synthetic ghrelin agonists, and the endogenous ghrelin signal-enhancer rikkunshito, which are expected to play significant roles in the clinical treatment and prevention of anorexia in future. © 2013 Elsevier Inc.

Mogami S.,Keio University | Mogami S.,Tsumura and Co. | Suzuki H.,Keio University | Tsugawa H.,Keio University | And 2 more authors.
Neurogastroenterology and Motility | Year: 2013

Background: Streptozotocin (STZ) is known to induce type I diabetes and the loss of the interstitial cells of Cajal (ICC). However, the regulation of heme oxygenase-1 (HO-1) expression, which is reported to protect ICC, has not yet been elucidated in this model. The aim of this study was to investigate the alterations of HO-1 expression and clarify the mechanism of ICC loss in the stomach using the rat model of STZ-induced diabetes. Methods: Streptozotocin (65 mg kg-1) was intraperitoneally administered to 8-week-old female Wistar rats. Cobalt protoporphyrin (CoPP), an HO-1 inducer, was administered subcutaneously once a week after the STZ injection. The expressions of HO-1 and the receptor tyrosine kinase c-Kit (a marker for ICC) proteins were investigated by western blot analysis and immunofluorescence staining. Key Results: Expression of c-Kit, particularly in the gastric antrum, was significantly decreased at 8 weeks, not at 1 week, compared to those of the control group. Significantly increased induction of HO-1 expression, especially in the gastric corpus but not in the antrum, was observed in the STZ group at 8 weeks after the STZ injection relative to control. CoPP administration significantly up-regulated HO-1 expression in the STZ diabetic group and significantly restored the previously reduced ICC in the gastric antrum. Conclusions & Inferences: Up-regulation of HO-1 expression in the STZ diabetic model was limited to the gastric corpus and impaired up-regulation of HO-1 expression in the gastric antrum likely induced the disruption of the ICC network. © 2013 John Wiley & Sons Ltd.

Fujitsuka N.,Tsumura and Co. | Uezono Y.,National Cancer Center Research Institute
Frontiers in Pharmacology | Year: 2014

Anorexia-cachexia syndrome develops during the advanced stages of various chronic diseases in which patients exhibit a decreased food intake, weight loss, and muscle tissue wasting. For these patients, this syndrome is a critical problem leading to an increased rate of morbidity and mortality. The present pharmacological therapies for treating anorexia-cachexia have limited effectiveness. The Japanese herbal medicine rikkunshito is often prescribed for the treatment of anorexia and upper gastrointestinal (GI) disorders. Thus, rikkunshito is expected to be beneficial for the treatment of patients with anorexia-cachexia syndrome. In this review, we summarize the effects of rikkunshito and its mechanisms of action on anorexia-cachexia. Persistent loss of appetite leads to a progressive depletion of body energy stores, which is frequently associated with cachexia. Consequently, regulating appetite and energy homeostasis is critically important for treating cachexia. Ghrelin is mainly secreted from the stomach, and it plays an important role in initiating feeding, controlling GI motility, and regulating energy expenditure. Recent clinical and basic science studies have demonstrated that the critical mechanism of rikkunshito underlies endogenous ghrelin activity. Interestingly, several components of rikkunshito target multiple gastric and central sites, and regulate the secretion, receptor sensitization, and degradation of ghrelin. Rikkunshito is effective for the treatment of anorexia, body weight loss, muscle wasting, and anxiety-related behavior. Furthermore, treatment with rikkunshito was observed to prolong survival in an animal model of cachexia. The use of a potentiator of ghrelin signaling, such as rikkunshito, may represent a novel approach for the treatment of anorexia-cachexia syndrome. © 2014 Fujitsuka and Uezono.

Mogami S.,Tsumura and Co. | Hattori T.,Tsumura and Co.
Evidence-based Complementary and Alternative Medicine | Year: 2014

Background. Kampo medicines are traditional herbal medicines which have been approved for medicinal use by the Japanese Ministry of Health and Welfare and are currently being used more and more, often in combination with Western drugs. Thus, the need for investigation of interactions between Kampo medicines and Western drugs is now widely recognized. Aim. To summarize the effects and drug interactions of rikkunshito, a Kampo medicine often prescribed for upper gastrointestinal disorders and anorexia. Methods. Animal and human studies were systematically reviewed to identify published data on rikkunshito. Results describing its effects were abstracted, with an emphasis on drug interactions. Results and Discussion. Rikkunshito ameliorates anorexia induced by anticancer drugs, improves quality of life scores, and can even prolong survival compared with monotherapy. Rikkunshito combined with proton pump inhibitor therapy is shown to be useful in the treatment of PPI-refractory gastroesophageal reflux disease patients and patients with gastrointestinal symptoms after endoscopic submucosal dissection. Rikkunshito reduces antidepressant-induced adverse events and improves quality of life without influencing antidepressant effects. Conclusions. Rikkunshito shows ameliorative effects on adverse reactions induced by various Western drugs and can achieve better results (e.g., anticancer drugs and proton pump inhibitor) without influencing the efficacy and bioavailability of Western drugs. © 2014 Sachiko Mogami and Tomohisa Hattori.

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