The mechanism by which rikkunshito increases acylated ghrelin

• Project/Area Number: 22590676
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hokkaido University
• Principal Investigator: TAKEDA Hiroshi 北海道大学, 大学院・薬学研究院, 教授 (60261294)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: グレリン・漢方 / グレリン / GOAT / 漢方薬 / 六君子湯

Research Abstract

This study was conducted to uncover the mechanism by which rikkunshito increases plasma acylatedto desacyl-ghrelin ratio in cisplatin-treated rats. Several components of rikkunsito including 10-gingeroldemonstrated inhibitory activity against ghrelin deacylating enzyme, carboxylesterase. Furthermore,stably transfected GOAT/ preproghrelin HEK 293 cells were successfully established to explore theeffects of rikkunshito on ghrelin producing machinery.

Research Products

• [Journal Article] Serotonin 2Creceptor antagonism ameliorates novelty- induced hypophagia in aged mice. (2013)
  • Author(s): Nahata M, Muto S, Nakagawa K, Ohnishi S, Sadakane C, Saegusa Y, Iizuka S, Hattori T, Asaka M, Takeda H.
  • Journal Title: Psychoneuroendocrinology. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Changes in ghrelin-related factors in gastroesophageal reflux disease in rats. (2013)
  • Author(s): Nahata M, Saegusa Y, Harada Y, Tsuchiya N, Hattori T, Takeda H.
  • Journal Title: Gastroenterology Research and Practice. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Cisplatin-induced anorexia and ghrelin. (2013)
  • Author(s): Hattori T, Yakabi K, Takeda H.
  • Journal Title: Vitam Horm Volume: 92 Pages: 301-317
  • Peer Reviewed
• [Journal Article] Comparison of Gastric Relaxation and Sensory Functions between Functional Dyspepsia and Healthy Subjects Using Novel Drinking-Ultrasonography Test. (2013)
  • Author(s): Hata T, Kato M, Kudo T, Nishida M, Nishida U, Imai A, Yoshida T, Hirota J, Kamada G, Ono S, Nakagawa M, Nakagawa S, Shimizu Y, Takeda H, Asaka M.
  • Journal Title: Digestion. Volume: 87 Pages: 34-39
  • NAID: 120005228164
  • Peer Reviewed
• [Journal Article] Rikkunshito and ghrelin secretion. (2012)
  • Author(s): Takeda H, Muto S, Nakagawa K, Ohnishi S, Asaka M.
  • Journal Title: Curr Pharm Des. Volume: 18 Pages: 4827-4838
  • Peer Reviewed
• [Journal Article] Rikkunshito as a ghrelin enhancer. (2012)
  • Author(s): Takeda H, Muto S, Nakagawa K, Ohnishi S, Sadakane C, Saegusa Y, Nahata M, Hattori T, Asaka M.
  • Journal Title: Methods Enzymol. Volume: 514 Pages: 333-351
• [Journal Article] Impaired ghrelin signaling is associated with gastrointestinal dysmotility in rats with gastroesophageal reflux disease. (2012)
  • Author(s): Nahata M, Muto S, Oridate N, Ohnishi S, Nakagawa K, Sadakane C, Saegusa Y, Hattori T, Asaka M, Takeda H.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol. Volume: 303
  • Peer Reviewed
• [Journal Article] Efficacy of carbon dioxide-insufflating colonoscopy in patients with irritable bowel syndrome (IBS): a randomized double-blind study. (2012)
  • Author(s): Imai A, Kato M, Ono S, Shimizu Y, Takeda H, Asaka M.
  • Journal Title: J Gastroenterol Hepatol. Volume: 27 Pages: 1623-1628
  • Peer Reviewed
• [Journal Article] 10-Gingerol, a component of rikkunshito, improves cisplatin -induced anorexia by inhibiting acylated ghrelin degradation. (2011)
  • Author(s): Sadakane C, Muto S, Nakagawa K, Ohnishi S, Saegusa Y, Nahata M, Hattori T, Asaka M, Takeda H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 412 Pages: 506-511
  • Peer Reviewed
• [Journal Article] Decreased plasma ghrelin contributes to anorexia following novelty stress. (2011)
  • Author(s): Saegusa Y, Takeda H, Muto S, Nakagawa K, Ohnishi S, Sadakane C, Nahata M, Hattori T, Asaka M.
  • Journal Title: Am J Physiol Endocrinol Metab. Volume: 301
  • NAID: 130004626089
  • Peer Reviewed
• [Journal Article] Decreased motility of the lower esophageal sphincter in a rat model of gastroesophageal reflux disease may be mediated by reductions of serotonin and acetylcholine signaling. (2011)
  • Author(s): Saegusa Y, Takeda H, Muto S, Oridate N, Nakagawa K, Sadakane C, Nahata M, Harada Y, Iizuka M, Hattori T, Asaka M.
  • Journal Title: Biol Pharm Bull. Volume: 34 Pages: 704-711
  • NAID: 130000657784
  • Peer Reviewed
• [Journal Article] Decreased plasma ghrelin contributes to anorexia following novelty stress (2011)
  • Author(s): Saegusa Y, Takeda H, Muto S, Nakagawa K, Ohnishi S, Sadakane C, Nahata M, Hattori T, Asaka M
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 301 Issue: 4 Pages: E685-E696
  • DOI: 10.1152/ajpendo.00121.2011
  • NAID: 130004626089
  • Peer Reviewed
• [Journal Article] 10-Gingerol, a component of rikkunshito, improves cisplatin-induced anorexia by inhibiting acylated ghrelin degradation (2011)
  • Author(s): Sadakane C, Muto S, Nakagawa K, Ohnishi S, Saegusa Y, Nahata M, Hattori T, Asaka M, Takeda H
  • Journal Title: Biochem Biophys Res Commun Volume: 412 Issue: 3 Pages: 506-511
  • DOI: 10.1016/j.bbrc.2011.08.002
  • Peer Reviewed
• [Journal Article] Rikkunshito ameliorates the aging-associated decrease in ghrelin receptor reactivity via phosphodiesterase III inhibition. (2010)
  • Author(s): Takeda H, Muto S, Hattori T, Sadakane C, Tsuchiya K, Katsurada T, Ohkawara T, Oridate N, Asaka M.
  • Journal Title: Endocrinology. Volume: 151 Pages: 244-252
  • Peer Reviewed
• [Journal Article] 機能性ディスペプシアおよび食欲不振に対する漢方治療 (2010)
  • Author(s): 武田宏司, 武藤修一, 大西俊介, 浅香正博
  • Journal Title: 日本消化器病学会雑誌 Volume: 107 Pages: 1586-1591
  • NAID: 10027493726
• [Journal Article] 消化器疾患に対する心身医学的アプローチ高齢者における食欲不振の病態 (2010)
  • Author(s): 武田宏司, 武藤修一
  • Journal Title: 日本医事新報 Volume: 4500 Pages: 76-80
  • NAID: 40017200498
• [Presentation] 機能性消化管障害の病態生理と治療戦略 (2013)
  • Author(s): 武田宏司
  • Organizer: 第9回日本消化管学会総会(ランチョンセミナー)
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2013-01-26
• [Presentation] グレリンシグナルの低下がGERDにおける胃排出低下に関与する (2012)
  • Author(s): 武田宏司、武藤修一、大西俊介
  • Organizer: JDDW2012(シンポジウム)
  • Place of Presentation: 神戸国際会議場他(兵庫県神戸市)
  • Year and Date: 2012-10-12
• [Presentation] セロトニン、グレリンシグナルと食欲の異常 (2012)
  • Author(s): 武田宏司
  • Organizer: 第16回活性アミンに関するワークショップ
  • Place of Presentation: 北海道医療大学(北海道札幌市)
  • Year and Date: 2012-08-24
• [Presentation] 癌患者における食欲不振のメカニズム (2012)
  • Author(s): 武田宏司
  • Organizer: 第53回日本心身医学会総会
  • Place of Presentation: かごしま県民交流センター(鹿児島県鹿児島市)
  • Year and Date: 2012-05-25
• [Presentation] A Study on Gender Differences in Feeding Behavior and Plasma Acyl Ghrelin Levels in Aged Mice Following Exposure to a Novel Environmental Stress. (2012)
  • Author(s): Ohnishi S, Takeda H, Muto S, Nakagawa K, Sadakane C, Nahata M, Saegusa Y, Hattori T, Asaka M.
  • Organizer: DDW2012.
  • Place of Presentation: San Diego Convention Center(米国カリフォルニア州サンディエゴ市)
  • Year and Date: 2012-05-20
• [Presentation] The Ghrelin Enhancer Rikkunshito Improves Gastric Dysmotility in Restraint Stress Mice. (2012)
  • Author(s): Takeda H, Muto S, Ohnishi S, Nakagawa K, Nahata M, Saegusa Y, Sadakane C, Hattori T, Asaka M.
  • Organizer: DDW2012.
  • Place of Presentation: San Diego Convention Center(米国カリフォルニア州サンディエゴ市)
  • Year and Date: 2012-05-19
• [Presentation] Potential New Treatment to Alleviate Stress-Induced Anorexia. (2012)
  • Author(s): Muto S, Takeda H, Ohnishi S, Nakagawa K, Saegusa Y, Nahata M, Sadakane C, Hattori T, Asaka M.
  • Organizer: DDW2012
  • Place of Presentation: San Diego Convention Center(米国カリフォルニア州サンディエゴ市)
  • Year and Date: 2012-05-19
• [Presentation] Stress-Related Differences in Appetite-Related Genes Between Advanced-Age Male and Female Mice. (2012)
  • Author(s): Muto S, Takeda H, Ohnishi S, Nakagawa K, Sadakane C, Saegusa Y, Nahata M, Hattori T, Asaka M.
  • Organizer: DDW2011
  • Place of Presentation: McCormick Place(米国イリノイ州シカゴ市)
  • Year and Date: 2012-05-07
• [Presentation] 社会的ストレスと消化器症状 (2012)
  • Author(s): 武田宏司、武藤修一、大西俊介
  • Organizer: 第78回消化器心身医学研究会(シンポジウム)
  • Place of Presentation: パークハイアット東京(東京)
  • Year and Date: 2012-04-20
• [Presentation] 性差が末梢グレリン分泌に与える影響 (2012)
  • Author(s): 大西俊介、武藤修一、武田宏司
  • Organizer: 98回日本消化器病学会(ワークショップ)
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2012-04-19
• [Presentation] 新奇環境ストレスによる食欲不振は血中グレリン低下が原因である (2012)
  • Author(s): 武藤修一、大西俊介、武田宏司
  • Organizer: 第8回日本消化管学会
  • Place of Presentation: 仙台国際センター(宮城県仙台市)
  • Year and Date: 2012-02-10
• [Presentation] 六君子湯の食欲改善作用のメカニズム (2011)
  • Author(s): 武田宏司、武藤修一、大西俊介
  • Organizer: 第13回日本神経消化器病学会総会(シンポジウム)
  • Place of Presentation: 栃木県総合文化センター(栃木県宇都宮市)
  • Year and Date: 2011-11-05
• [Presentation] 六君子湯は社会的隔離による食欲不振を改善する (2011)
  • Author(s): 武田宏司,武藤修一,大西俊介
  • Organizer: 第97回日本消化器病学会総会(ワークショップ)
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2011-05-14
• [Presentation] 六君子湯は社会的隔離による食欲不振を改善する (2011)
  • Author(s): 武田宏司, 武藤修一, 大西俊介
  • Organizer: 第97回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2011-05-14
• [Presentation] Novelty Stress-Induced Anorexia is Due to the Decrease in the Plasma Ghrelin Level via 5-HT1b/2C-Melanocortin4 System Activation. (2011)
  • Author(s): Muto S, Takeda H, Ohnishi S, Nakagawa K, Sadakane C, Saegusa Y, Nahata M, Hattori T, Asaka M.
  • Organizer: DDW2011
  • Place of Presentation: McCormick Place(米国イリノイ州シカゴ市)
  • Year and Date: 2011-05-10
• [Presentation] Potential New Treatment to Alleviate Chemotherapy Anorexia. (2011)
  • Author(s): Ohnishi S, Takeda H, Muto S, Nakagawa K, Sadakane C, Saegusa Y, Nahata M, Hattori T, Asaka M.
  • Organizer: DDW2011
  • Place of Presentation: McCormick Place(米国イリノイ州シカゴ市)
  • Year and Date: 2011-05-10
• [Presentation] Impaired Gastric Emptying in Gastroesophageal Reflux Disease Rat Models is Caused by a Reduced Response to Ghrelin. (2011)
  • Author(s): Takeda H, Muto S, Oridate N, Ohnishi S, Nakagawa K, Sadakane C, Saegusa Y, Nahata M, Sadakane C, Hattori T, Asaka M.
  • Organizer: DDW2011
  • Place of Presentation: McCormick Place(米国イリノイ州シカゴ市)
  • Year and Date: 2011-05-08
• [Presentation] Influence of Gender on Peripheral Ghrelin Secretion-Examination in the Aging Mice-. (2011)
  • Author(s): Ohnishi S, Takeda H, Muto S, Nakagawa K, Sadakane C, Saegusa Y, Nahata M, Hattori T, Asaka M.
  • Organizer: DDW2011
  • Place of Presentation: McCormick Place(米国イリノイ州シカゴ市)
  • Year and Date: 2011-05-07
• [Presentation] 腹部膨満の病態と大建中湯の役割 (2011)
  • Author(s): 武田宏司、加藤寛士、浅香正博
  • Organizer: 第7回日本消化管学会総会
  • Place of Presentation: 国立京都国際会館(京都府京都市)
  • Year and Date: 2011-02-19
• [Presentation] 加齢による食欲不振のメカニズムとその対策 (2010)
  • Author(s): 武藤修一、平山剛、武田宏司
  • Organizer: JDDW2010(シンポジウム)
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2010-10-14
• [Presentation] 消化器疾患と六君子湯・大建中湯 (2010)
  • Author(s): 武田宏司
  • Organizer: 第12回日本神経消化器病学会(市民講座)
  • Place of Presentation: 鹿児島大学稲盛会館(鹿児島県鹿児島市)
  • Year and Date: 2010-10-02
• [Presentation] 食欲不振に対する六君子湯の効果 (2010)
  • Author(s): 武田宏司、武藤修一、大西俊介、浅香正博
  • Organizer: 第12回日本神経消化器病学会総会(シンポジウム)
  • Place of Presentation: 城山観光ホテル(鹿児島県鹿児島市)
  • Year and Date: 2010-10-01
• [Presentation] Social Isolation After Anorexia is Mediated by Abnormalities in Serotonin 2C Receptor Reactivity. (2010)
  • Author(s): Sadakane C, Takeda H, Saegusa Y, Hattori T, Nakagawa K, Muto S, Asaka M.
  • Organizer: DDW2010.
  • Place of Presentation: The Ernest N. Morial Convention Center(米国ルイジアナ州ニューオリンズ市)
  • Year and Date: 2010-05-05
• [Presentation] Ghrelin Alleviates Social Isolation-Associated Anorexia in Mice. (2010)
  • Author(s): Saegusa Y, Takeda H, Sadakane C, Hattori T, Katsurada T, Muto S, Asaka M.
  • Organizer: DDW2010.
  • Place of Presentation: The Ernest N. Morial Convention Center(米国ルイジアナ州ニューオリンズ市)
  • Year and Date: 2010-05-03
• [Presentation] 消化器癌化学療法にともなう食欲不振のメカニズムとその対策 (2010)
  • Author(s): 武藤修一、武田宏司、浅香正博
  • Organizer: 第96回日本消化器病学会総会シンポジウム
  • Place of Presentation: 新潟市朱鷺メッセ(新潟県新潟市)
  • Year and Date: 2010-04-23
• [Presentation] 食欲の科学 (2010)
  • Author(s): 武田宏司
  • Organizer: 第96回日本消化器病学会総会(ランチョンセミナー)
  • Place of Presentation: 新潟市朱鷺メッセ(新潟県新潟市)
  • Year and Date: 2010-04-23
• [Presentation] 消化器癌化学療法にともなう食欲不振のメカニズム (2010)
  • Author(s): 武藤修一、武田宏司、浅香正博
  • Organizer: 第96回日本消化器病学会総会
  • Place of Presentation: 新潟
  • Year and Date: 2010-04-23
• [Presentation] グレリンシグナルの低下がGERDにおける胃排出低下に関与する
  • Author(s): 武田宏司、武藤修一、大西俊介
  • Organizer: JDDW2012
  • Place of Presentation: 神戸国際会議場他（兵庫県神戸市）
• [Presentation] 社会的ストレスと消化器症状
  • Author(s): 武田宏司
  • Organizer: 第53回日本心身医学会総会
  • Place of Presentation: かごしま県民交流センター（鹿児島県鹿児島市）
  • Invited
• [Presentation] セロトニン、グレリンシグナルと食欲の異常
  • Author(s): 武田宏司
  • Organizer: 第16回活性アミンに関するワークショップ
  • Place of Presentation: 北海道医療大学（北海道札幌市）
  • Invited
• [Remarks]
  • URL: http://www.pharm.hokudai.ac.jp/byoutai/index.html