Intragastric administration of rikkunshito stimulates upper gastrointestinal motility and gastric emptying in conscious dogs

Yanai, Mitsuhiro; Mochiki, Erito; Ogawa, Atsushi; Morita, Hiroki; Toyomasu, Yoshitaka; Ogata, Kenichi; Tabe, Yuichi; Ando, Hiroyuki; Ohno, Tetsuro; Asao, Takayuki; Aomori, Tohru; Fujita, Yukiyoshi; Kuwano, Hiroyuki

doi:10.1007/s00535-012-0687-8

Cited by 43 publications

(43 citation statements)

References 34 publications

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“…Additionally, increasing evidence from experimental animal models has shown that rikkunshito ameliorates several types of anorexia (23,24,57). It has been reported that with rikkushito there is an increase in the secretion of the orexigenic hormone ghrelin by the inhibition of 5-HT2B/2C receptors, an enhancement of ghrelin receptor (GHSR) signaling efficiency, and a facilitation of gastric emptying and gastric adaptive relaxation, all of which may contribute to ameliorate anorexia (24,32,57,60,64). Herein, we examined specifically the efficacy of rikkunshito in ameliorating anorexia symptoms in our novel cancer cachexia rat models.…”

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confidence: 99%

New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line

Terawaki

Sawada²,

Kashiwase

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Cancer cachexia (CC), a syndrome characterized by anorexia and body weight loss due to low fat-free mass levels, including reduced musculature, markedly worsens patient quality of life. Although stomach cancer patients have the highest incidence of cachexia, few experimental models for the study of stomach CC have been established. Herein, we developed stomach CC animal models using nude rats subcutaneously implanted with two novel cell lines, i.e., MKN45c185, established from the human stomach cancer cell line MKN-45, and 85As2, derived from peritoneal dissemination of orthotopically implanted MKN45c185 cells in mice. Both CC models showed marked weight loss, anorexia, reduced musculature and muscle strength, increased inflammatory markers, and low plasma albumin levels; however, CC developed earlier and was more severe in rats implanted with 85As2 than in those implanted with MKN45cl85. Moreover, human leukemia inhibitory factor (LIF), a known cachectic factor, and hypothalamic orexigenic peptide mRNA levels increased in the models, whereas hypothalamic anorexigenic peptide mRNA levels decreased. Surgical removal of the tumor not only abolished cachexia symptoms but also reduced plasma LIF levels to below detectable limits. Importantly, oral administration of rikkunshito, a traditional Japanese medicine, substantially ameliorated CC-related anorexia and body composition changes. In summary, our novel peritoneal dissemination-derived 85As2 rat model developed severe cachexia, possibly caused by LIF from cancer cells, that was ameliorated by rikkunshito. This model should provide a useful tool for further study into the mechanisms and treatment of stomach CC. cachexia; leukemia inhibitory factor; rikkunshito; stomach cancer model; anorexia CANCER CACHEXIA, A MULTIFACTORIAL SYNDROME characterized by anorexia and the loss of body weight, adipose tissue, and skeletal muscle, is observed in 80% of advanced cancer patients and accounts for at least 20% of cancer-related deaths (20,35,42). This syndrome causes not only poor quality of life (QOL) but also poor responses to chemotherapy, highlighting the need for improved cancer cachexia treatments. Weight loss, the most prominent clinical feature of cachexia, is observed in 30 -80% of cancer patients, depending on tumor type. For example, weight loss occurs at a very high frequency (83%) in stomach and pancreatic cancer patients but is less prominent in patients with breast cancer, acute nonlymphocytic leukemia, and sarcomas (35). Although cachexia strongly impacts the success of therapeutic treatments, the mechanisms underlying this syndrome are not fully understood. Stomach cancer patients in particular have the highest incidence of cachexia; however, few experimental models for the study of stomach cancer cachexia have been established (4,14,66).A useful cachexia model must meet three of the following five diagnostic criteria in addition to weight loss: anorexia, decreased muscle strength, fatigue, low fat-free mass (FFM) index, and abnormal biochemistry (anemia, in...

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confidence: 99%

New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line

Terawaki

Sawada²,

Kashiwase

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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“…Ghrelin is expressed by GHRL gene, several SNP are informed for it. In literature is actively studied the SNP allele polymorphism with obesity [10,11], food behavior disorders [12] and metabolism disturbances [13], and also with gastric acid secretion [14] and fast stomach emptying [15,16]. Mutations in this gene can cause low levels of ghrelin, registered at obesity [17].…”

Section: Introductionmentioning

confidence: 99%

Р. Leu72met Mutation of Ghrelin GHRL Gene in Children With Gastroesophageal Reflux Disease

Dats-Opoka

Makukh

Hnateyko

2017

EUREKA: Health Sciences

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Gastroesophageal disease (GERD) is the one of most spread diseases that injures an esophagus. Taking into account the large number of factors that can cause GERD development already in child age, including genetic predisposition, it is necessary to analyze each of them in detail. Aim of this work was to analyze a frequency and possible association type of р. Leu72Met mutation of GHRL gene in children with gastroesophageal reflux disease. The analysis of clinical parameters and course of disease in the group of 100 schoolchildren with GERD was carried out. The molecular-genetic study of c.214C>A locus of GHRL gene by CPR method (rs696217) was carried out in patients with GERD and 40 healthy children from the control group. In 82% of children with GERD was revealed a GHRL 214СС (Leu/Leu) homozygous genotype, at 58% among children from the control group. GHRL 214СА (Leu/ Met) genotype was registered three times more seldom in children of the studied group comparing with ones from the control group: 15,0% and 42,5%, respectively. It was established, that GHRL 214CС genotype presence conditions the increase of GERD development risk in 3,4 times. On the contrary, GHRL 214CА genotype manifests a reliable protective effect that is essentially decreased GERD development risk in a child at such genotype – 0,24 comparing with a conventional unit. There was established alleles and genotypes distribution of c.214C>A (р.Leu72Met) locus of GHRL gene in children with GERD. GHRL 214CС genotype is associated with threefold increase of GERD risk development. Gender differences as to GERD development risk at different genotypes of ghrelin gene were established. At GHRL 214СС (Leu/Leu) genotype the relative GERD risk for boys increased in more than 6 times. There were not established any differences in alleles and genotypes distribution depending on erosive or surface inflammatory changes of a gastrointestinal tract mucosa.

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“…Thus, we were able to compare the effects of various reagents in the same animals. In this context, four to six dogs have been used in recent studies from our institution (Hayashi et al 2010;Sato et al 2010a) and other institutions (Dong et al 2005;Morita et al 2012;Yanai et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Intragastric Dai-Kenchu-To, a Japanese Herbal Medicine, Stimulates Colonic Motility via Transient Receptor Potential Cation Channel Subfamily V Member 1 in Dogs

Kikuchi

Shibata

Imoto

et al. 2013

Tohoku J. Exp. Med.

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Japanese herbal medicine, also known as Kampo, is used for various diseases in Japan. One of those medicines, Dai-Kenchu-To (DKT), is considered clinically effective for adhesive bowel obstruction and chronic constipation. Although scientific evidence of DKT to improve adhesive bowel obstruction was shown in several previous reports, mechanism of DKT to improve constipation remains unknown. Our aim was to study the effect of intragastric DKT on colonic motility and defecation, and the involvement of various receptors in DKT-induced colonic contractions. Five beagle dogs were instructed with serosal strain-gauge force transducers to measure circular muscle activity at the proximal, middle, and distal colon. Dogs are suitable for a present study to administer the drugs repeatedly to the same individual and look at its effect on colonic motility. We studied the effects of DKT (2.5 or 5 g) administered into the stomach on colonic motility. Muscarinic receptor antagonist atropine, nicotinic receptor antagonist hexamthonium, or 5-hydroxytryptamine-3 receptor antagonist ondansetron was injected intravenously 10 min before DKT administration. Capsazepine, an antagonist to transient receptor potential cation channel subfamily V member 1 (TRPV1), was administered into the stomach 5 min before DKT administration. Intragastric DKT (2.5 or 5 g) induced colonic contractions within 10 min after administration but did not induce defecation. Pretreatment with atropine, hexamthonium, ondansetron, or capsazepine inhibited DKT-induced colonic contractions. These results indicate that orally administered DKT stimulates colonic motility via TRPV1, muscarinic, nicotinic, and 5-hydroxytryptamine-3 receptors, thereby providing scientific support for the efficacy of oral DKT in chronic constipation.

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Intragastric administration of rikkunshito stimulates upper gastrointestinal motility and gastric emptying in conscious dogs

Cited by 43 publications

References 34 publications

New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line

New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line

Р. Leu72met Mutation of Ghrelin GHRL Gene in Children With Gastroesophageal Reflux Disease

Intragastric Dai-Kenchu-To, a Japanese Herbal Medicine, Stimulates Colonic Motility via Transient Receptor Potential Cation Channel Subfamily V Member 1 in Dogs

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