Rikkunshito, a ghrelin potentiator, ameliorates anorexiaâ€“cachexia syndrome

Fujitsuka, Naoki; Uezono, Yasuhito

doi:10.3389/fphar.2014.00271

Cited by 56 publications

(65 citation statements)

References 88 publications

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“…Anorexia-cachexia syndrome is reported in the advanced stages of cancer [106]. This syndrome is a cause of patients' increased rate of morbidity and mortality [107].…”

Section: Cancer Anorexia-cachexiamentioning

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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“…Anorexia-cachexia syndrome is reported in the advanced stages of cancer [106]. This syndrome is a cause of patients' increased rate of morbidity and mortality [107].…”

Section: Cancer Anorexia-cachexiamentioning

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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“…In cancer cachexia-associated anorexia, ghrelin has drawn much attention because of its role in the regulation of gastrointestinal activity and energy consumption. 10) Our findings indicate that impaired mastication should also be considered as a cause of anorexia.…”

Section: Discussionmentioning

confidence: 61%

Effects of Combined Treatment with Branched-Chain Amino Acids, Citric Acid, L-Carnitine, Coenzyme Q10, Zinc, and Various Vitamins in Tumor-Bearing Mice

Awa

Futamura

Higashiguchi

et al. 2017

Biological & Pharmaceutical Bulletin

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A functional dietary supplement (FDS) containing Coenzyme Q10, branched-chain amino acids and L-carnitine was administered to tumor-bearing mice, investigating its effects on tumor and muscle tissues. Experiment (A): B16 melanoma cells were implanted subcutaneously into the right side of the abdomen of 8-to 9-week-old C57BL/6J mice. The mice were divided into two groups: a FDS group that received oral administration of FDS (n=10), and a control group that received oral administration of glucose (n=10). The moribund condition was used as the endpoint, and median survival time was determined. Experiment (B): On day 21 after tumor implantation, tumors, soleus muscle, gastrocnemius muscle, and suprahyoid muscles were collected. Tumor and muscle weight and other aspects were evaluated in each group: FDS group (n=15) and control group (n=15). The median survival time was comparable (21 d in the FDS group vs. 18 d in the control group, p=0.30). However, cumulative food intake was significantly higher in the FDS group than the control group (p=0.011). Metastasis of melanoma to the lung was observed in the control group but not in the FDS group (p=0.043). The weight of the suprahyoid muscles was significantly higher in the FDS group than in the control group (p=0.0045). The weight of the tumor was significantly lower in the FDS group than in the control group (p=0.013). The results possibly suggest oral administration of FDS in tumor-bearing mice enhances the maintenance of suprahyoid muscles, resulting in an extended feeding period and suppression of tumor growth and metastasis.Key words cancer therapy; cachexia; metabolism; branched-chain amino acid; functional maintenance Cancer cachexia is a syndrome that affects many patients with advanced cancer. It is characterized by refractory malnutrition and has significant impact on prognosis and QOL. Managing cachexia is therefore a high priority when providing palliative care. Cachexia is a complex metabolic syndrome, with loss of muscle mass being a primary symptom. Development of cachexia involves many factors and accompanies progressive functional impairment, but the pathogenesis remains unknown. 1,2) Recent studies suggest that metabolic and neuroendocrinological abnormalities in cancer cachexia are caused by inflammatory cytokines secreted by the tumor and host cells and other tumor-derived substances. It is essential for cancer patients to maintain good nutritional status for better prognosis and QOL. As such, managing cancer cachexia is a major goal for the future of cancer therapy and palliative care. Since its foundation in 2003, our laboratory has implemented a unique nutritional support system to manage cancer cachexia.3-5) With the nutritional support, patients with cachexia have shown reduced symptoms and improved bodily function through control of metabolic dynamics. We have developed a functional dietary supplement (FDS) for improving symptoms and function, containing Coenzyme Q10 (CoQ10), branchedchain amino acids (BCAA), L-carnitine and citric acid and repo...

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“…However, treatment with Rikkunshito, a ghrelin potentiator, was observed to prolong survival in an animal model of cachexia 73 , and in a rodent model of cancer cachexia induced by Lewis Lung Carcinoma (LLC) tumor implantation, ghrelin administration prevented the development of cachexia (lean and fat mass loss) and this was associated with improved survival 39 .…”

Section: 6 Long Term Effectsmentioning

confidence: 99%

Anamorelin hydrochloride for the treatment of cancer-anorexia-cachexia in NSCLC

Zhang

García

2015

Expert Opinion on Pharmacotherapy

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Introduction Cancer anorexia-cachexia syndrome (CACS) is associated with increased morbidity and mortality. Anamorelin is a novel, orally active ghrelin receptor agonist in clinical development for the treatment of CACS in non-small cell lung cancer (NSCLC). The aim of this review is to summarize preclinical and clinical studies evaluating anamorelin as a potential promising treatment for CACS in NSCLC. Area covered Pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety, and tolerability of anamorelin for the treatment of CACS in NSCLC were reviewed. Anamorelin administration may lead to increases in food intake, body weight and lean body mass, and a stimulatory effect on GH secretion in NSCLC patients. Anamorelin is well tolerated with no dose-limiting toxicities identified to date. Expert opinion Targeting ghrelin receptors presents the advantage of potentially addressing multiple mechanisms of CACS simultaneously including appetite, muscle protein balance, adipose tissue metabolism, energy expenditure and inflammation. Clinical data suggest that anamorelin is well tolerated and it effectively increases appetite, body weight and lean mass in patients with advanced NSCLC. Long-term safety remains unknown at this time. The potential synergistic effects of anamorelin with nutritional support or exercise as well as its efficacy/safety in other tumor types are also unknown.

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Rikkunshito, a ghrelin potentiator, ameliorates anorexiaâ€“cachexia syndrome

Cited by 56 publications

References 88 publications

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

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

Effects of Combined Treatment with Branched-Chain Amino Acids, Citric Acid, L-Carnitine, Coenzyme Q10, Zinc, and Various Vitamins in Tumor-Bearing Mice

Anamorelin hydrochloride for the treatment of cancer-anorexia-cachexia in NSCLC

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