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Home > Organization > Divisions and Independent Research Units > Group for Translational Research > Division of Cancer Pathophysiology > Research Projects > Analysis of sites of action of Japanese herbal kampo medicine for the treatment of late-stage cancer patients and for reducing side effects caused by chemotherapy

Analysis of sites of action of Japanese herbal kampo medicine for the treatment of late-stage cancer patients and for reducing side effects caused by chemotherapy

We established novel cancer cachexia animal models, and then undertook molecular and cellular analyses to identify the mechanisms of action of the expected compounds to improve the QOL of patients suffering from cancer cachexia. For instance, we found a Japanese Kampo (traditional Oriental) medicine "rikkunshito" usually administered for the prevention of gastritis, nausea, and vomiting, improved the symptoms of cancer cachexia. In addition to rikkunshito, we analyzed and summarized the action mechanisms of other traditional Japanese Kampo medicines to improve chemotherapy-induced side effects such as pain and allodynia.

We recently demonstrated that rikkunshito prolonged survival in mouse models of human aging by activation of ghrelin signal and subsequent sirtuin 1 signal, the important protein for longevity, suggesting that potentiation of this signal with rikkunshito may be helpful to extend health and lifespan.


Recent publication related to research for kampo medicines

  • Ohnishi S, Watari H, Kanno M, Ohba Y, Takeuchi S, Miyaji T, Oyamada S, Nomura E, Kato H, Sugiyama T, Asaka M, Sakuragi N, Yamaguchi T, Iwase S, Uezono Y. Additive effect of rikkunshito, an herbal medicine, on chemotherapy-induced nausea, vomiting, and anorexia in uterine cervical or corpus cancer patients treated with cisplatin and paclitaxel: results of a randomized phase II study (JORTC KMP-02). J Gynecol Oncol, 28: e44, 2017.
  • Terawaki K, Kashiwase Y, Sawada Y, Hashimoto H, Yoshimura M, Ohbuchi K, Sudo Y, Suzuki M, Miyano K, Shiraishi S, Higami Y, Yanagihara K, Hattori T, Kase Y, Ueta Y, Uezono Y. Development of ghrelin resistance in a cancer cachexia rat model using human gastric cancer-derived 85As2 cells and the palliative effects of the kampo medicine rikkunshito on the model. PLoS One, 12: e0173113, 2017. (PMID: 28249026)
  • Tagami K, Kashiwase Y, Yokoyama A, Nishimura H, Miyano K, Suzuki M, Shiraishi S, Matoba M, Ohe Y, Uezono Y. The atypical antipsychotic, olanzapine, potentiates ghrelin-induced receptor signaling: an in vitro study with cells expressing cloned human growth hormone secretagogue receptor. Neuropeptides, 58: 93-101, 2016. (PMID: 26775231)
  • Fujitsuka N, Asakawa A, Morinaga A, Amitani MS, Amitani H, Katsuura G, Sawada Y, Sudo Y, Uezono Y, Mochiki E, Sakata I, Sakai T, Hanazaki K, Yada T, Yakabi K, Sakuma E, Ueki T, Niijima A, Nakagawa K, Okubo N, Takeda H, Asaka M, Inui A. Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1. Mol Psychiatry, 21: 1613-1623, 2016. (PMID: 26830139)
  • Kono T, Shimada M, Yamamoto M, Kaneko A, Oomiya Y, Kubota K, Kase Y, Lee K, Uezono Y. Complementary and synergistic therapeutic effects of multicomponents in daikenchuto. Front Pharmacol, 6: 159, 2015.
  • Kitagawa H, Munekage M, Matsumoto T, Sadakane C, Fukutake M, Aoki K, Watanabe J, Maemura K, Hattori T, Kase Y, Uezono Y, Inui A, Hanazaki K. Pharmacokinetic profiles of active ingredients and its metabolites derived from rikkunshito, a ghrelin enhancer, in healthy Japanese volunteers: A cross-over, randomized study. PLoS One, 10: e0133159, 2015. [PubMed](外部リンク)
  • Kubota K, Ohtake N, Ohbuchi K, Mase A, Imamura S, Sudo Y, Miyano K, Yamamoto M, Kono T, Uezono Y. Hydroxy-α-sanshool evokes unique colonic migrating motor complex in rat proximal colon via blocking of KCNK9. Am J Physiol Gastrointest Liver Physiol, 308: G579-G590, 2015. [PubMed](外部リンク)
  • Kono T, Takeda H, Shimada M, Kase Y, Uezono Y. Novel therapeutics for adverse effects of antitumor therapy: The promise of multicomponent, traditional Japanese herbal remedies. J Carcinog Mutagen, S8: 007, 2014. (http://www.omicsonline.org/open-access/novel-therapeutics-for-adverse-effects-of-antitumor-therapy-the-promise-of-multicomponent-traditional-japanese-herbal-remedies-2157-2518-S8-007.php?aid=24656)(外部リンク)
  • Fujitsuka N, Uezono Y. Rikkunshito, a ghrelin potentiator, ameliorates anorexia-cachexia syndrome. Front Pharmacol, 5: 271, 2014. [PubMed](外部リンク)
  • Kono T, Kaneko A, Matsumoto C, Miyagi C, Ohbuchi K, Mizuhara Y, Miyano K, Uezono Y. Multitargeted effects of hangeshashinto for treatment of chemotherapy-induced oral mucositis on inducible prostaglandin E2 production in human oral keratinocytes. Integr Cancer Ther, 13: 435-445, 2014. [PubMed](外部リンク)
  • Nagamura Y, Terawaki K, Uezono Y, Tsukada T. Enhancement of catecholamine release from PC12 cells by the traditional Japanese medicine, rikkunshito. BMC Complement Altern Med, 14: 256, 2014. (http://www.ncbi.nlm.nih.gov/pubmed/?term=Uezono+Y+AND+Nagamura+Y)(外部リンク)
  • Mizuno K, Kono T, Suzuki Y, Miyagi C, Omiya Y, Miyano K, Kase Y, Uezono Y. Goshajinkigan, a traditional Japanese medicine, prevents oxaliplatin-induced acute peripheral neuropathy by suppressing functional alteration of TRP channels in rat. J Pharmacol Sci, 125: 91-98, 2014. [PubMed](外部リンク)
  • Terawaki K, Sawada Y, Kashiwase Y, Hashimoto H, Yoshimura M, Suzuki M, Miyano K, Sudo Y, Shiraishi S, Higami Y, Yanagihara K, Kase Y, Ueta Y, Uezono Y. New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line. Am J Physiol Endocrinol Metab, 306: E373-E387, 2014. [PubMed](外部リンク)
  • Yoshimura M, Hagimoto M, Matsuura T, Ohkubo J, Ohno M, Maruyama T, Ishikura T, Hashimoto H, Kakuma T, Yoshimatsu H, Terawaki K, Uezono Y, Toyohira Y, Yanagihara N, Ueta Y. Effects of food deprivatation on the hypothalamic feeding-regulating peptides gene expressions in serotonin depleted rats. J Physiol Sci, 64: 97-104, 2014. [PubMed](外部リンク)
  • Yanagihara K, Takigahira M, Mihara K, Kubo T, Morimoto C, Morita Y, Terawaki K, Uezono Y. Inhibitory effects of isoflavones on tumor growth and cachexia in newly established cachectic mouse models carrying human stomach cancers. Nutr Cancer, 65: 578-589, 2013. [PubMed](外部リンク)
  • Iwase S, Yamaguchi T, Miyaji T, Terawaki K, Inui A, Uezono Y. The clinical use of Kampo medicines (traditional Japanese herbal treatments) for controlling cancer patients' symptoms in Japan: a national cross-sectional survey. BMC Complement Altern Med, 12: 222, 2012. [PubMed](外部リンク)
  • Uezono Y, Miyano K, Sudo Y, Suzuki M, Shiraishi S, Terawaki K. A review of traditional Japanese medicines and their potential mechanism of action. Curr Pharm Des, 18: 4839-4853, 2012. [PubMed](外部リンク)
  • Fujitsuka N, Asakawa A, Uezono Y, Minami K, Yamaguchi T, Niijima A, Yada T, Maejima Y, Sedbazar U, Sakai T, Hattori T, Kase Y, Inui A. Potentiation of ghrelin signaling attenuates cancer anorexia-cachexia and prolongs survival. Transl Psychiatr, 1: e23, 2011. [PubMed](外部リンク)