Exploration of food functionality of Dioscorea japonica targeting lipid mediator

• Project/Area Number: 24500948
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits, studies on eating habits
• Research Institution: Okayama Prefectural University
• Principal Investigator: TOSHIKO Suzuki-Yamamoto 岡山県立大学, 保健福祉学部, 准教授 (60301313)
• Co-Investigator(Renkei-kenkyūsha): INOUE Hiroyasu 奈良女子大学, 生活環境学部, 教授 (40183743) ; YAMAMOTO Kei 財団法人東京都医学総合研究所, 主席研究員 (30304504) ; KAWAKAMI Yuki 岡山県立大学, 保健福祉学部, 助教 (30453202)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 脂質メディエーター / PGE2 / COX-2 / mPGES-1 / 炎症 / 癌 / 自然薯 / 食品機能性 / 抗炎症 / 抗腫瘍

Outline of Final Research Achievements

In this study, we investigated novel functions of Dioscorea japonica on the related enzymes synthesizing prostaglandin (PG) E2. PGE2 is one of the lipid mediators, and is involved in many pathophysiological conditions such as inflammation and tumorigenesis. Under the conditions, PGE2 is synthesized from arachidonic acid by cyclooxygenase (COX)-2 and microsomal PGE synthase (mPGES)-1. Dioscorea japonica extract (DJE) suppressed COX-2 and mPGES-1 in carcinoma A549 and Caco-2 cells, and inflammatory RAW264 cells. DJE induced cancer cells to apoptosis, and suppressed inflammatory cytokines. In mouse model of squamous cell carcinoma of the skin, Dioscorea japonica inhibited tumor formation, suppressed COX-2 and mPGES-1, and decreased subepidermal eosinophils and neutrophils. These results indicate that Dioscorea japonica may have preventive effects against inflammation and tumorigenesis via suppression of PGE2 synthesis pathway.

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] <i>Dioscorea japonica</i> 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. Biochem. Nutr. Volume: 55(3) Issue: 3 Pages: 162-167
  • DOI: 10.3164/jcbn.14-25
  • NAID: 130004687668
  • ISSN: 0912-0009, 1880-5086
  • 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
  • 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
  • NAID: 120005397778
  • Peer Reviewed
• [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. Nurosci. Res. Volume: in press
  • Peer Reviewed
• [Journal Article] Dioscorea japonica extract suppresses the expression of the related enzymes synthesizing lipid mediator prostaglandin E2. (2013)
  • Author(s): Tsukayama I, Takafuji M, Tanaka S, Kawakami Y, Takahashi Y, Suzuki-Yamamoto T.
  • Journal Title: Ann. Nutr. Metab. Volume: 63 (suppl1) Pages: 1597-1597
• [Journal Article] Proteomic analysis of arginine methylated proteins in rat brain. (2013)
  • Author(s): Kimoto M, Hatanaka H, Suzuki-Yamamoto T, Suzuki M, Ito A, Yokoro M, Yamashita H, Takahashi Y.
  • Journal Title: Ann. Nutr. Metab. Volume: 63 (suppl1) Pages: 327-327
• [Journal Article] Antiatherogenic effect of guava leaf extracts inhibiting leucocyte-type 12-lipoxygenase activity (2012)
  • Author(s): Yuki Kawakami, et al
  • Journal Title: Food Chemistry Volume: 131 Pages: 1069-1075
  • DOI: 10.1016/j.foodchem.2011.10.011
  • 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
• [Presentation] Inhibitory effect of Qing Shan Lu Shui Tea on leukocyte-type 12-lipoxygenase activity. (2014)
  • Author(s): Yuki Kawakami, Akemi Otsuki, Yoshiko Mori, Hideyuki Ito, Toshiko Suzuki-Yamamoto, Hideaki Tsuji, Ding Zhi Fang, Yoshitaka Takahashi.
  • Organizer: ISNFF2013
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Preventive effect of Dioscorea japonica on squamous cell carcinoma of the skin. (2014)
  • Author(s): Toshiko Suzuki-Yamamoto, Izumi Tsukayama, Miki Takafuji, Takuto Mega, Kanako Nakatani, Yuri Wada, Sayaka Hamasaki, Makiko Suzuki, Yuki Kawakami, Yoshitaka Takahashi.
  • Organizer: Okayama Prefectural University-Nanchang University Workshop for Food and Nutritional Sciences,
  • Place of Presentation: Okayama, Japan
• [Presentation] Dioscorea japonica extract suppresses the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in lung carcinoma A549 cells and macrophage-like RAW264 cells. (2014)
  • Author(s): Izumi Tsukayama, Sayuri Tanaka, Risako Takiuchi, Miki Takafuji, Keisuke Toda, Mitsuki Tanaka, Toshiya Arakawa, Yuki Kawakami, Masumi Kimoto, Yoshitaka Takahashi, Toshiko Suzuki-Yamamoto.
  • Organizer: Okayama Prefectural University-Nanchang University Workshop for Food and Nutritional Sciences,
  • Place of Presentation: Okayama, Japan
• [Presentation] Inhibitory effect of tea extracts on leukocyte-type 12-lipoxygenase activity. (2014)
  • Author(s): Yuki Kawakami, Akemi Otsuki, Mai Kinoshita, Yoshiko Mori, Makiko Suzuki, Toshiko Suzuki-Yamamoto, Masumi Kimoto, Hideaki Tsuji, Hiromi Yamashita, Hideyuki Ito, Ding Zhi Fang, Yoshitaka Takahashi.
  • Organizer: Okayama Prefectural University-Nanchang University Workshop for Food and Nutritional Sciences,
  • Place of Presentation: Okayama, Japan
• [Presentation] 自然薯のプロスタグランジンE2合成系抑制と皮膚癌モデルにおける抗腫瘍効果． (2014)
  • Author(s): 山本登志子、津嘉山泉、高藤美樹、瀧内理紗子、鈴木麻希子、荒川俊哉、川上祐生、高橋吉孝．
  • Organizer: 第68回日本栄養・食糧学会大会
  • Place of Presentation: 札幌
• [Presentation] Dioscorea japonica extract suppresses the expression of the related enzymes synthesizing lipid mediator prostaglandin E2. (2013)
  • Author(s): Izumi Tsukayama, Miki Takafuji, Sayuri Tanaka, Yuki Kawakami, Yoshitaka Takahashi and Toshiko Suzuki-Yamamoto.
  • Organizer: IUNS 20th International Congress of Nutrition
  • Place of Presentation: Granada, Spain
• [Presentation] Proteomic Analysis of Arginine Methylated Proteins in Rat Brain. (2013)
  • Author(s): Kimoto M, Hatakenaka H, Suzuki-Yamamoto T, Suzuki M, Ito A, Yokoro M, Yamashita H, Takahashi Y.
  • Organizer: IUNS 20th International Congress of Nutrition
  • Place of Presentation: Granada, Spain
• [Presentation] Dioscorea japonica extract suppresses COX-2 and mPGES-1 expression and has preventive effects against squamous cell carcinoma. (2013)
  • Author(s): Toshiko Suzuki-Yamamoto, Izumi Tsukayama, Miki Takafuji, Sayuri Tanaka, Yuki Kawakami, Yoshitaka Takahashi.
  • Organizer: 16th GEM/10th GERLI lipidomics meeting: from membranes to pathologies.
  • Place of Presentation: Saint-Jean-Cap-Ferrat, France
• [Presentation] 白血球型12-リポキシゲナーゼに対する中国茶葉抽出物の阻害効果. (2013)
  • Author(s): 川上祐生、大槻朱美、平野詩織、木下麻衣、山本登志子、辻英明、木本眞順美、山下広美、伊東秀之、Ding Zhi Fang、高橋吉孝.
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 仙台
• [Presentation] 部位特異的変異体を用いた抗ロイコトリエンC4単鎖抗体の抗原結合に関与するアミノ酸の同定. (2013)
  • Author(s): 木下麻衣、勝原加奈子、川上祐生、山本登志子、菅原光明、堀哲哉、齊野廣道、宮野雅司、山本尚三、高橋吉孝.
  • Organizer: 第86回日本生化学会
  • Place of Presentation: 横浜
• [Presentation] 中国茶に含まれる白血球型12-リポキシゲナーゼ阻害成分の解析. (2013)
  • Author(s): 大槻朱美、森香子、森ひとみ、李鵬、川上祐生、山本登志子、辻英明、伊東秀之、方定志、高橋吉孝.
  • Organizer: 第86回日本生化学会
  • Place of Presentation: 横浜
• [Presentation] マウス海馬におけるタンパク質の非対称性アルギニンメチル化に及ぼす加齢と高脂肪食の影響. (2013)
  • Author(s): 鈴木麻希子，守谷智恵，山本登志子，山下広美，高橋吉孝，坪井誠二,辻英明，木本眞順美.
  • Organizer: 第86回日本生化学会
  • Place of Presentation: 横浜
• [Presentation] マウス海馬におけるタンパク質の非対称性アルギニンメチル化に及ぼす加齢と高脂肪食の影響. (2013)
  • Author(s): 鈴木麻希子，守谷智恵，山本登志子，山下広美，高橋吉孝，辻英明，木本眞順美.
  • Organizer: 第６７回日本栄養・食糧学会大会
  • Place of Presentation: 名古屋
• [Presentation] 自然薯抽出物によるシクロオキシゲナーゼ－２と膜結合型プロスタグランジンE合成酵素-1の発現抑制． (2013)
  • Author(s): 津嘉山泉，田中小百合，高藤美樹，吉尾壯兒，川上祐生，高橋吉孝，山本登志子.
  • Organizer: 第６７回日本栄養・食糧学会大会
  • Place of Presentation: 名古屋
• [Presentation] ラット組織におけるアルギニンメチル化タンパク質の検索と同定. (2013)
  • Author(s): 森本亮祐，大森由香子，鈴木麻希子，野村奈央，山本登志子，山下広美，高橋吉孝，木本眞順美.
  • Organizer: 第４６回日本栄養・食糧学会中国・四国支部大会
  • Place of Presentation: 山口
• [Presentation] 自然薯抽出物によるシクロオキシゲナーゼ－２と膜結合型プロスタグランジンE合成酵素-1の発現抑制 (2013)
  • Author(s): 津嘉山泉，田中小百合，高藤美樹，吉尾壯兒，川上祐生，高橋吉孝，山本登志子
  • Organizer: 第６７回日本栄養食糧学会大会
  • Place of Presentation: 名古屋
• [Presentation] Dioscorea japonica extract suppresses the expression of the related enzymes synthesizing lipid mediator prostaglandin E2 (2013)
  • Author(s): Izumi Tsukayama, Miki Takafuji, Sayuri Tanaka, Yuki Kawakami, Yoshitaka Takahashi and Toshiko Suzuki-Yamamoto
  • Organizer: IUNS 20th International Congress of Nutrition
  • Place of Presentation: Granada, Spain
• [Presentation] Inhibitory effect of Chinese tea on leukocyte-type 12-lipoxygenase activity. International Conference on Biologically Active Substances (2012)
  • Author(s): Akemi Otsuki, Shiori Hirano, Mai Kinoshita, Ichika Shimoda, Yuki Kawakami, Toshiko Suzuki-Yamamoto, Hideaki Tsuji, Hideyuki Ito, Ding Zhi Fang and Yoshitaka Takahashi
  • Organizer: International Conference on Biologically Active Substances, Bioactive Okayam BAO2012
  • Place of Presentation: Okayama, Japan
• [Presentation] Dioscorea japonica extract suppresses the expression of COX-2 and prostaglandin E synthase. (2012)
  • Author(s): Izumi Tsukayama, Miki Takayama, Sayuri Tanaka, Yuki Kawakami, Yoshitaka Takahashi and Toshiko Suzuki-Yamamoto.
  • Organizer: International Conference on Biologically Active Substances, Bioactive Okayam BAO2012
  • Place of Presentation: Okayama, Japan
• [Presentation] 中国茶に含まれる白血球型12-リポキシゲナーゼ阻害成分の解析. (2012)
  • Author(s): 川上祐生、大槻朱美、平野詩織、木下麻衣、下田一花、山本登志子、辻英明、木本眞順美、伊東秀之、Ding Zhi Fang、高橋吉孝
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] ロイコトリエン単鎖抗体を利用した炎症性疾患治療薬の開発を目指した研究.
  • Author(s): 木下麻衣，大槻朱美，森香子，勝原加奈子，川上祐生，山本登志子，高橋吉孝.
  • Organizer: 第43回おかやまバイオアクティブシンポジウム 2013.
  • Place of Presentation: 岡山
• [Presentation] 白血球型12-リポキシゲナーゼを阻害する新規化合物の解明.
  • Author(s): 大槻朱美，森香子，木下麻衣，勝原加奈子，森ひとみ，李鵬，川上祐生，山本登志子，辻英明，伊東秀之，Ding Zhi Fang，高橋吉孝.
  • Organizer: 第43回おかやまバイオアクティブシンポジウム 2013.
  • Place of Presentation: 岡山
• [Presentation] 自然薯抽出物のプロスタグランジンＥ2合成系抑制による抗炎症・抗腫瘍効果.
  • Author(s): 津嘉山泉、田中小百合、高藤美樹、瀧内理紗子、川上祐生、高橋吉孝、山本登志子.
  • Organizer: 第44回おかやまバイオアクティブシンポジウム 2013.
  • Place of Presentation: 岡山
• [Presentation] 新規モノテルペン配糖体による白血球型 12-リポキシゲナーゼ阻害．
  • Author(s): 川上祐生，大槻朱美，森香子，伊東秀之，山本登志子，辻 英，DingZhiFang，高橋吉孝．
  • Organizer: 52 回日本油化学会年会 2013
  • Place of Presentation: 仙台
• [Presentation] ヒドロペルオキシ基を持つ新規モノテルペン配糖体による白血球型12-リポキシゲナーゼの阻害.
  • Author(s): 川上祐生、大槻朱美、木下麻衣、森香子、山本登志子、辻英明、伊東秀之、FANG Ding Zhi、高橋吉孝.
  • Organizer: 日本過酸化脂質・抗酸化物質学会 第21回年会.
  • Place of Presentation: 仙台