自然薯の脂質メディエーターをターゲットとした食品機能性の探索

2014 Fiscal Year Annual Research Report

• Project/Area Number: 24500948
• Research Institution: Okayama Prefectural University
• Principal Investigator: 山本 登志子(鈴木登志子) 岡山県立大学, 保健福祉学部, 准教授 (60301313)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 脂質メディエーター / PGE2 / COX-2 / mPGES-1 / 自然薯 / 癌 / 炎症

Outline of Annual Research Achievements

本研究では、炎症や癌の惹起に関わる脂質メディエーターのPGE2合成系をターゲットとした食品機能性の探索を行ってきた。
これまでの実験から、自然薯抽出物によるシクロオキシゲナーゼ（COX）-2と膜結合型PGE合成酵素(mPGES)-1の発現抑制によって、PGE2産生低下にともなう抗炎症・抗腫瘍効果を、癌や炎症のモデル細胞、あるいは、炎症をともなう皮膚癌モデルマウスにおいて明らかにした。皮膚癌モデルマウスにおいては、自然薯の経口摂取と抽出物塗布のいずれでも、COX-2とmPGES-1の発現抑制と腫瘍形成抑制や炎症性細胞の浸潤低下ならびに、炎症性サイトカインや炎症性脂質メディエーターの産生低下が明らかとなった。さらに、大腸癌モデルとアトピー性皮膚炎モデルに対する効果についても実施し、現在解析中である。
このような効果を有する自然薯抽出物から、その効果に寄与する機能生成分を同定するために、各種クロマトグラフィーを用いて分析したところ、少なくともCOX-2に対する効果を有する成分は2つ存在した。その一つが植物ステロールのジオスゲニンであることを明らかにし、効果を検証したところ、COX-2に対しては発現抑制効果を有するものの、その程度は自然薯抽出物よりも弱く、また、mPGES-1に対しては有意な効果が認められなかった。このことから、自然薯抽出物で観察された効果は、いくつかの機能性成分の複合的な効果であることが考えられ、現在さらに別の機能生成分についても分析を進めているところである。

Research Products

• [Journal Article] 4.脂質メディエーター合成系をターゲットとした抗炎症・高腫瘍効果を有する食品機能性の探索． (2015)
  • Author(s): 山本 登志子、津嘉山 泉、武田 泰典、目賀 拓斗、戸田 圭祐、田中 充樹．
  • Journal Title: アサヒグループ学術振興財団 研究紀要 Volume: 27 Pages: 7-15
  • Acknowledgement Compliant
• [Journal Article] Dioscorea japonica extract down-regulates prostaglandin E2 synthetic pathway and induces apoptosis in lung cancer cells. (2014)
  • Author(s): Suzuki-Yamamoto T, Tanaka S, Tsukayama I, Takafuji M, Hanada T, Arakawa T, Kawakami Y, Kimoto M, Takahashi Y.
  • Journal Title: J. Clin.Biol.Nutri. Volume: 55(3) Pages: 162-167
  • DOI: 10.3164/jcbn.14-25.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cellular localization of 5a-reductasein the rat cerebellum. (2014)
  • Author(s): Kiyokage E, Toida K, Suzuki-Yamamoto T, Kazunori I.
  • Journal Title: J. Chem. Neuroanat. Volume: 59 Pages: 8-16
  • DOI: 0.1016/j.jchemneu.2014.04.002.
  • Peer Reviewed
• [Journal Article] Neutralization of leukotriene C4 and D4 activity by monoclonal and single-chain antibodies. (2014)
  • Author(s): Kawakami Y, Hirano S, Kinoshita M, Otsuki A, Suzuki-Yamamoto T; Suzuki M, Kimoto M, Sasabe S, Fukushima M, Kishimoto K, Izumi T, Oga T, Narumiya S, Sugahara M, Miyano M, Yamamoto S, Takahashi Y.
  • Journal Title: Biochim Biophys Acta. Volume: 1840 Pages: 1625-1633
  • DOI: 10.1016/j.bbagen.2013.12.016.
  • Peer Reviewed
• [Journal Article] Food functionality of the diet containing Dioscorea japonica powder targeting bioactive lipid synthesis pathway (2014)
  • Author(s): Suzuki-Yamamoto T, Tanaka S, Tsukayama I, Ohmoto A, Yoshio S, Kawakami Y, Kimoto M, Takahashi Y.
  • Journal Title: Bulletin of Faculty of Health and Welfare Science, Okayama Prefectural University Volume: 20 Pages: 37-44
  • Peer Reviewed
• [Presentation] Dioscorea japonica extract suppresses cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in lung carcinoma A549 cells. (2015)
  • Author(s): Keisuke Toda, Izumi Tsukayama, Takuto Mega, Yuka Konoike, Toshiya Arakawa, Yuki Kawakami, Masumi Kimoto, Yoshitaka Takahashi, Toshiko Suzuki-Yamamoto.
  • Organizer: 14th International Conference of Bioactive Lipids in Cancer, Inflammation and Related Diseases.
  • Place of Presentation: Budapest, Hungary.
  • Year and Date: 2015-07-12 – 2015-07-15
• [Presentation] Preventive effect of Dioscorea japonica on squamous cell carcinoma of the mouse skin involving down-regulation of prostaglandin E2 synthetic pathway. (2015)
  • Author(s): Izumi Tsukayama, Yasunori Takeda , Takuto Mega, Keisuke Toda, Yuki Kawakami, Yoshitaka Takahashi, Masumi Kimoto, Kei Yamamoto, Makoto Murakami, Toshiko Suzuki-Yamamoto.
  • Organizer: 14th International Conference of Bioactive Lipids in Cancer, Inflammation and Related Diseases.
  • Place of Presentation: Budapest, Hungary.
  • Year and Date: 2015-07-12 – 2015-07-15
• [Presentation] Purification and characterization of bovine lipocalin-type prostaglandin D synthase from cow’s milk. (2015)
  • Author(s): Toshiko Suzuki-Yamamoto, Mitsuki Tanaka, Erika Kawai, Keisuke Toda, Yui Serai, Takuto Mega, Yuki Kawakami, Yoshitaka Takahashi, Kei Yamamoto, Makoto Murakami, Masumi Kimoto.
  • Organizer: 14th International Conference of Bioactive Lipids in Cancer, Inflammation and Related Diseases.
  • Place of Presentation: Budapest, Hungary.
  • Year and Date: 2015-07-12 – 2015-07-15
• [Presentation] Preventive effect of Dioscorea japonica on squamous cell carcinoma of mouse skin. (2015)
  • Author(s): Yasunori Takeda, Izumi Tsukayama, Takuto Mega, Keisuke Toda, Mitsuki Tanaka, Yuki Kawakami, Yoshitaka Takahashi, Kei Yamamoto, Makoto Murakami, Toshiko Suzuki-Yamamoto.
  • Organizer: 12th Asian Congress of Nutrition
  • Place of Presentation: Yokohama, Japan.
  • Year and Date: 2015-05-14 – 2015-05-18
• [Presentation] Dioscorea japonica extract suppresses cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in lung carcinoma A549 cells and macrophage-like RAW264 cells. (2015)
  • Author(s): Keisuke Toda, Izumi Tsukayama, Takuto Mega, Mitsuki Tanaka, Yasunori Takeda, Toshiya Arakawa, Yuki Kawakami, Masumi Kimoto, Yoshitaka Takahashi, Toshiko Suzuki-Yamamoto.
  • Organizer: 12th Asian Congress of Nutrition
  • Place of Presentation: Yokohama, Japan.
  • Year and Date: 2015-05-14 – 2015-05-18
• [Presentation] Dioscorea japonica suppresses COX-2 and mPGES-1 expression and has preventive effects on squamous cell carcinoma. (2015)
  • Author(s): Izumi Tsukayama, Yasunori Takeda, Kanako Nakatani, Takuto Mega, Keisuke Toda, Yuki Kawakami, Yoshitaka Takahashi, Toshiya Arakawa, Kei Yamamoto, Makoto Murakami, Toshiko Suzuki-Yamamoto.
  • Organizer: 6th International Conference on Phosphplipaze A2 and Lipid Medoators (PLM2015)
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] Prevention by food functionalities targeting prostaglandin E2 synthesis pathway on inflammation and carcinogenesis. (2014)
  • Author(s): Suzuki-Yamamoto, T.
  • Organizer: The Conference on Food and Nutrition Science among Sichuan University, Nanchang University, Woosong University, and Okayama Prefectural University
  • Place of Presentation: Chengdu, China.
  • Year and Date: 2014-09-12
  • Invited
• [Presentation] Inhibition of leukocyte-type 12-lipoxygenase activity by Chinese tea. (2014)
  • Author(s): Yoshiko Mori, Akemi Otsuki, Shuji Okochi, Kensuke Okamoto, Yuki Kawakami, Toshiko Suzuki-Yamamoto, Hideaki Tsuji, Hideyuki Ito, Ding Zhi Fang, Yoshitaka Takahashi.
  • Organizer: The Conference on Food and Nutrition Science among Sichuan University, Nanchang University, Woosong University, and Okayama Prefectural University
  • Place of Presentation: Chengdu, China.
  • Year and Date: 2014-09-12
• [Presentation] Monoclonal and single-chain antibodies neutralize biological activities of leukotriene C4 and D4. (2014)
  • Author(s): Yuki Kawakami, Mai Kinoshita, Yoshiko Mori, Shuji Okochi, Kensuke Okamoto, Sae Sasabe, Toshiko Suzuki-Yamamoto, Hiromi Yamashita, Masumi Kimoto, Mitsuo Fukushima, Hideaki Tsuji, Yoshitaka Takahashi.
  • Organizer: The Conference on Food and Nutrition Science among Sichuan University, Nanchang University, Woosong University, and Okayama Prefectural University
  • Place of Presentation: Chengdu, China.
  • Year and Date: 2014-09-12
• [Presentation] 40S ribosomal protein subunit 2 is a major arginine methylated protein in rat tissues. (2014)
  • Author(s): Ryosuke Morimoto, Toshiko Suzuki-Yamamoto, Sayaka Yamamoto, Nao Nomura, Yoshitaka Takahashi, Hiromi Yamashita, Masumi Kimoto.
  • Organizer: The Conference on Food and Nutrition Science among Sichuan University, Nanchang University, Woosong University, and Okayama Prefectural University
  • Place of Presentation: Chengdu, China.
  • Year and Date: 2014-09-12
• [Presentation] Dioscorea japonica extract suppressed the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in lung carcinoma A549 cells and macrophage-like RAW 264 cells. (2014)
  • Author(s): Izumi Tsukayama, Takuto Mega, Keisuke Toda, Yasunori Takeda, Yuki Kawakami, Masumi Kimoto, Yoshitaka Takahashi, Toshiko Suzuki-Yamamoto.
  • Organizer: The Conference on Food and Nutrition Science among Sichuan University, Nanchang University, Woosong University, and Okayama Prefectural University
  • Place of Presentation: Chengdu, China.
  • Year and Date: 2014-09-12