Clinical efficacy and its molecular mechanisms of ninjinyoeito on oxaliplatin-induced peripheral neuropathy

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590669
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: Kanazawa Medical University
• Principal Investigator: MOTOO Yoshiharu 金沢医科大学, 医学部, 教授 (80210095)
• Co-Investigator(Kenkyū-buntansha): SAIKI Ikuo 富山大学, 和漢医薬学総合研究所, 教授 (80133776) ; TAKANO Fumihide 日本薬科大学, 薬学部, 准教授 (20236251) ; MAKINO Toshikaki 名古屋市立大学, 大学院・薬学研究科, 准教授 (80326561)
• Co-Investigator(Renkei-kenkyūsha): ISHIGAKI Yasuhito 金沢医科大学, 総合医学研究所, 准教授 (20232275) ; SHIMASAKI Takeo 金沢医科大学, 総合医学研究所, 講師 (50377420)
• Project Period (FY): 2010 – 2012
• Keywords: 大腸癌 / オキサリプラチン / 末梢神経障害 / 人参養栄湯 / 漢方

Research Abstract

In a pilot clinical trial, ninjinyoeito (NYT) was administered to 22 patients with advanced or recurrent colorectal cancer from the beginning of FOLFOX or XELOX, which contained oxaliplatin (L-OHP). Maximal peripheral neuropathy was grade2 in all patients during the observation period. In a mouse model, L-OHP (i.p.)induced cold hypersensitivity and mechanical allodynia, but NYT significantly attenuated these findings. In PC12 cells, L-OHP shortened nerve growth factor-induced neurite outgrowth, which NYT (300 μg/ml) recovered.

Research Products

• [Journal Article] Traditional Japanese medicine in the multidisciplinary approach to cancer. (2012)
  • Author(s): Motoo Y.
  • Journal Title: J Trad Med Volume: 29(2) Pages: 104-107
  • URL: http://aimc.edu/2012/02/traditional-japanese-medicine-in-the-multi-disciplinary-approach-to-cancer/
  • Peer Reviewed
• [Journal Article] Anti-austerity agents from Uvaria dac and their preferential cytotoxic activity against human pancreatic cancer cell lines in nutrient deprived condition. (2012)
  • Author(s): Awale S,Ueda J,Athikomkulchai S,Abdelhamed S,Yokoyama S,Saiki I,Miyatake R.
  • Journal Title: J Nat Prod Volume: 75 Pages: 1177-1183
  • DOI: Doi:10.1021/np300295h.
  • Peer Reviewed
• [Journal Article] Gomisin A enhances TNF-α-induced G1 cell cycle arrest via STAT1-mediated phosphorylation of retinoblastoma protein. (2012)
  • Author(s): Waiwut P,ShinM- S,Yokoyama S,Saiki I,Sakurai H.
  • Journal Title: Biol Pharm Bull Volume: 35 Pages: 1997-2003
  • Peer Reviewed
• [Journal Article] Traditional Japanese medicine,Kampo:its history and current status. (2011)
  • Author(s): Motoo Y,Seki T.Tsutani K.
  • Journal Title: Chin J Integr Med Volume: 17(2) Pages: 85-87
  • DOI: Doi:10.1007/s11655-011-0653-y.
  • Peer Reviewed
• [Journal Article] Metabolic Disorder,Inflammation,and Deregulated Molecular Pathways Convergingin Pancreatic Cancer Development:Implications for New Therapeutic Strategies. (2011)
  • Author(s): Motoo Y,Shimasaki T,Ishigaki Y,Nakajima H,Kawakami K,Minamoto T.
  • Journal Title: Cancers Volume: 3(1) Pages: 446-460
  • DOI: Doi:10.3390/cancers3010446
  • Peer Reviewed
• [Journal Article] Gomisin N enhancesT NF-α-induced apoptosis via inhibitionof NF-κ B and EGFR survival pathways. (2011)
  • Author(s): Waiwut P,Shin M S,Inujima A,Zhou Y,Koizumi K,Saiki I,Sakurai H.
  • Journal Title: Mol Cell Biochem Volume: 350 Pages: 169-175
  • DOI: Doi:10.1007/s11010-010-0695-z.
  • Peer Reviewed
• [Journal Article] Effect of hachimijiogan against renal dysfunction and involvement of hypoxia inducible factor-1α in the remnant kidney model. (2011)
  • Author(s): Nakamura S,Tsuneyama K,Zhou Y,Jo M,Sakurai H,Shibahara N,Saiki I,Shimada Y.
  • Journal Title: Evid Based Complement Alternat Med Volume: 348686 Pages: 1-9
  • DOI: Doi:10.1155/2011/348686.
  • Peer Reviewed
• [Journal Article] A Kampo Medicine, Boiogito, Inhibits Obesityin Ovariectomized Rats. (2010)
  • Author(s): Yamakawa J,Moriya J,Takahashi T,Ishige A,Motoo Y,Yoshizaki F,Kanda T.
  • Journal Title: Evidence-based complementary and alternative medicine(eCAM) Volume: 7(1) Pages: 87-95
  • DOI: Doi:10.1093/ecam/neml153.
  • Peer Reviewed
• [Presentation] Proteomic identification of biomarkers for diagnosis and treatment of traditional Japanese (Kampo) medicine. (2012)
  • Author(s): Saiki I.Keynote Lecture
  • Organizer: The 4th Conferenceon Traditional Medicinein ASEAN countries 2Towards Harmonisationof Traditional Medicine Practices"
  • Place of Presentation: Kuala Lumpur,Malaysia
  • Year and Date: 2012-11-26
• [Presentation] Curucumin and cancer metastasis,Joint seminaron (2012)
  • Author(s): Saiki I
  • Organizer: Recent Advancesin Natural Productsand Biotechnology
  • Place of Presentation: Cairo, Egypt
  • Year and Date: 2012-10-31
• [Presentation] Curucumin and cancer metastasis, International Symposium (2012)
  • Author(s): Saiki I.
  • Organizer: Medicinal Plantand Natural Product Research Traditionaland Modern Aspects
  • Place of Presentation: Ulaanbaatar, Mongolia
  • Year and Date: 2012-09-19
• [Presentation] Gomisin N Enhances Tumor Necrosis Factor- Related Apoptosis- Inducing Ligand (TRAIL)- Induced Apoptosis. (2012)
  • Author(s): Inoue H,Sakurai H,Nogami N,Fujimoto M,Hikiami H,Shibahara N,Saiki I,Shimada Y.
  • Organizer: 16 th International Congressof Oriental Medicine(ICOM)
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2012-09-15
• [Presentation] Japanese viewpoint on ICTM Interventions. (2011)
  • Author(s): Motoo Y,Arai I,Hakamatsuka T.
  • Organizer: Informal Consultationon Interventions Modeling
  • Place of Presentation: Geneva, Switzerland
  • Year and Date: 2011-12-12
• [Presentation] Kampo Therapyf or CancerCare Significanceas Supportive Measure (2011)
  • Author(s): Ogawa K,Ogawa M,Motoo Y.
  • Organizer: The First International Symposium for Japanese Kampo Medicine
  • Place of Presentation: Munich,Germany
  • Year and Date: 2011-11-25
• [Presentation] EvidenceReportsonKampoTreatment(EKAT) (2011)
  • Author(s): MotooY,AraiI,TsutaniK.
  • Organizer: TheFirstInternationalSymposiumforJapaneseKampoMedicine
  • Place of Presentation: Munich, Germany
  • Year and Date: 2011-11-25
• [Presentation] Evaluation of Japanese clinical practice guidelines based on Kampo descriptions. (2011)
  • Author(s): Motoo Y.
  • Organizer: Guidelines International Network Conference 2011
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2011-08-29
• [Presentation] Preventionofchemotherapy-inducedtransformationofcancercells. (2011)
  • Author(s): Motoo Y.
  • Organizer: 2011CPMDRCInternationalSymposiumCancerPreventionandPhytochemicals
  • Place of Presentation: Seoul,Korea
  • Year and Date: 2011-08-26
• [Presentation] Japanese view point of ISO/TC249. (2011)
  • Author(s): Motoo Y.
  • Organizer: The Second Plenary Meetingof ISO/TC249
  • Place of Presentation: The Hague,the Netherlands
  • Year and Date: 2011-05-02
• [Presentation] Chemo the rapy for pancreatic cancer:Molecular analysis and clinical application. (2011)
  • Author(s): Motoo Y.
  • Organizer: Asian Oncology Summit 2011"GISymposium3
  • Place of Presentation: Hong Kong SAR, China
  • Year and Date: 2011-04-09
• [Presentation] Proposal of comparative analysis of herbal medicines among C JK and alignment of the ICTM Herbal Interventions with other international initiatives. (2011)
  • Author(s): Motoo Y.
  • Organizer: WHO ICTMTAG Classification of Interventions
  • Place of Presentation: Hong Kong SAR,China
  • Year and Date: 2011-04-02
• [Presentation] Curcumin and Cancer Metastasis. (2010)
  • Author(s): Saiki I,Ohashi Y,Tsuchiya Y,Koizumi K,Sakurai H.
  • Organizer: The 9 th Joint Seminar"Natural Medicine Research for the Next Decade:New Challenges and Future Collaboration",NRCT-JSPS Core University ProgramonNatural Medicinein Pharmaceutical Sciences
  • Place of Presentation: Bankok
  • Year and Date: 2010-12-08
• [Presentation] Gomisin Nenhances TNF-□-induced apoptosis via inhibition of the NF-□B and EGFR survival pathways. (2010)
  • Author(s): Waiwut P,ShinM- S,Inujima A,Koizumi K,Saiki I,Sakurai H.
  • Organizer: The9thJointSeminar"NaturalMedicineResearchfortheNextDecade:NewChallengesandFutureCollaboration",NRCT-JSPSCoreUniversityProgramonNaturalMedicineinPharmaceuticalSciences.2010
  • Place of Presentation: Bankok
  • Year and Date: 2010-12-08
• [Presentation] The Controlling of Lymphangiogenesis. (2010)
  • Author(s): Prangsaengtong O,Koizumi K,Senda K,Urano T,Nagata A,Sakurai H,Tohda C,Saiki I.
  • Organizer: The 9th Joint Seminar"Natural Medicine Research for the Next Decade: New Challengesand Future Collaboration",NRCT-JSPS Core University Programon Natural Medicinein Pharmaceutical Sciences
  • Place of Presentation: Bankok, Thailand
  • Year and Date: 2010-12-08
• [Presentation] Molecular mechanisms of cross-talk between TNF-□and EGFR signaling pathways.Konkuk University Chungju 30t Anniversary (2010)
  • Author(s): ShinM- S,Saiki I,Sakurai H.
  • Organizer: 2010InternationalSymposiumonBiomedicalandHelthScience&4thAnnualSymposiumofCollageBiomedicalandHealthScience
  • Place of Presentation: Chungju, Korea
  • Year and Date: 2010-10-27
• [Presentation] Curcumin and cancer metastasis.Konkuk University Chungju 30th Anniversary (2010)
  • Author(s): Saiki I.
  • Organizer: 2010 International Symposiumon Biomedical and Helth Science & 4 th Annual Symposiumof Collage Biomedical and Health Science
  • Place of Presentation: Chungju, Korea
  • Year and Date: 2010-10-27
• [Presentation] A ginseng sapon in metabolitesppressesTNF-〓-promoted metastasis by suppressing NF-〓B signaling. (2010)
  • Author(s): Saiki I,ChooM-K,KimD-H,Sakurai H.
  • Organizer: The 10th International Symposiumon Ginseng.-〓Ginseng,the Root of Human Well-being〓2010
  • Place of Presentation: Seoul,Korea
  • Year and Date: 2010-09-14
• [Presentation] Current status of cancert reatment in Japan. (2010)
  • Author(s): Motoo Y.
  • Organizer: Academic lecture series on cancer:basic and clinical aspects
  • Place of Presentation: Shanghai,China
  • Year and Date: 2010-09-05
• [Presentation] enhances TNF induced apoptosis via inhibition of NF-kB and EGFR survival pathways. (2010)
  • Author(s): Waiwut P,ShinM-S,Inujima A,Koizumi K,Saiki I,Sakurai H.Gomisin N
  • Organizer: 第27回和漢医薬学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2010-08-29
• [Presentation] Juzentaihoto-induced inhibition of cancer metastasis-Establishment of molecular basisforKampomedicine-.Sympojium 8:Strategies and problem of Asian traditional medicine in cancer treatment (2010)
  • Author(s): Saiki I.
  • Organizer: 9th International Conference of the Asian Clinical Oncology Society"Talk to the world wide from Asia"-Multidisciplinary treatment for Asiancancer patients-
  • Place of Presentation: Gifu
  • Year and Date: 2010-08-26
• [Presentation] Resveratrol improves hippocampal atrophy in mice with chronic fatigue by enhancing neurogenesis and inhibiting apoptosis of granularcells. (2010)
  • Author(s): Moriya J,Yamakawa J,Motoo Y.
  • Organizer: The 9th Meeting of Consortium for Globalization of Chinese Medicine (CGCM)
  • Place of Presentation: Hong Kong SAR,China
  • Year and Date: 2010-08-23
• [Presentation] The role of eNOS-Hsp90 interaction and Calpain 1 involvement in lymphangiogenesis in vitro. (2010)
  • Author(s): Prangsaengtong O,Koizumi K,Sakurai H,Saiki I.
  • Organizer: The 6th International Conferenceon the Biology,Chemistry,and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Kyoto
  • Year and Date: 2010-06-05
• [Book] Traditional Medicine:New Research (2013)
  • Author(s): Ogawa-Ochiai K,Ogawa M,Motoo Y.
  • Total Pages: 1-14
  • Publisher: Nova Science Publishers
• [Book] Traditional Medicine: New Research (2013)
  • Author(s): Waiwut P,Inoue H,Saiki I,Sakurai H
  • Total Pages: 147-157
  • Publisher: Nova Science Publishers
• [Book] 治療薬ハンドブック薬剤選択と処方のポイント2013 (2013)
  • Author(s): 元雄良治
  • Total Pages: 1390-1435
  • Publisher: じほう
• [Book] The Primo Vascular System:Its Role in Cancer and Regeneration (2012)
  • Author(s): Motoo Y,Xia QS,Nakaya N,Shimasaki T,Nakajima H,Ishigaki Y.
  • Total Pages: 213-217
  • Publisher: Springer
• [Book] In:Colorectal cancer biology from genes to tumor (2012)
  • Author(s): Minamoto T,Kotake M,Nakada M,Shimasaki T,Motoo Y,Kawakami K.
  • Total Pages: 107-134
  • Publisher: InTech
• [Book] 治療薬ハンドブック薬剤選択と処方のポイント2012 (2012)
  • Author(s): 元雄良治
  • Total Pages: 1369-1372
  • Publisher: じほう
• [Book] がん漢方 (2012)
  • Author(s): 済木育夫
  • Total Pages: 110-122
  • Publisher: 南山堂
• [Book] 消化器がん化学療法ハンドブック (2011)
  • Author(s): 中島日出夫,元雄良治
  • Total Pages: 25-36
  • Publisher: 中外医学社
• [Book] がん転移‐臨床と研究の羅針盤‐細胞工学別冊 (2010)
  • Author(s): 櫻井宏明,小泉桂一,済木育夫.
  • Total Pages: 139-143
  • Publisher: 秀潤社