Study on the prenylflavonoids suppressing to advanced glycation end products, and preventing to diabetic complication.

• Project/Area Number: 26460141
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Sojo University
• Principal Investigator: IKEDA Tsuyoshi 崇城大学, 薬学部, 教授 (80295138)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 糖化終末化合物 / 糖尿病合併症 / プレニルフラボノイド / イカリソウ / 終末糖化生成物 / 生成阻害 / CML / CMA / フラボノイド

Outline of Final Research Achievements

Because advanced glycation end products (AGEs) are reported that involved in the pathogenesis and progression of lifestyle-related diseases and aging diseases, treatment with AGEs inhibitors is believed to be a potential strategy for the prevention of these diseases. Accordingly, we have been searched for natural products that inhibits the formation of AGEs. In our previous study, MeOH extract of Epimedii Herba (EH) was found to inhibit the formation of AGEs during incubation of collagen-derived gelatin with ribose.
Epimedokoreanin B (EKB) which was typical prenylflavonoid from EH was found having most strong inhibitory activity among the tested samples. This result was able to demonstrate the potential of anti-glycation effect in EH in addition to the traditional tonic effect. Furthermore the development of foodstuff including EKB is expected as a supplement, tea or cosmetics with anti-glycation action.

Research Products

• [Journal Article] Eucommia ulmoides extracts prevent the formation of advanced glycation end products. (2016)
  • Author(s): Sugawa Hikari, Ohno Rei-ichi, Shirakawa Jun-ichi, Nakajima Akari, Kanagawa Amane, Hirata Tetsuya, Ikeda Tsuyoshi, Moroishi Narumi, Nagai Mime, Nagai Ryoji
  • Journal Title: Food & Function Volume: 7(6) Issue: 6 Pages: 2566-2573
  • DOI: 10.1039/c5fo01563d
  • Peer Reviewed
• [Journal Article] Onionin A, a sulfur-containing compound isolated from onions, impairs tumor development and lung metastasis by inhibiting the protumoral and immunosuppressive functions of myeloid cells (2016)
  • Author(s): Fujiwara Yukio, Horlad Hasita, Shiraishi Daisuke, Tsuboki Junko, Kudo Rino, Ikeda Tsuyoshi, Nohara Toshihiro, Takeya Motohiro, Komohara Yoshihiro
  • Journal Title: Molecular Nutrition & Food Research Volume: 60(11) Issue: 11 Pages: 2467-2480
  • DOI: 10.1002/mnfr.201500995
  • Peer Reviewed
• [Journal Article] Antimicrobial and Immunomodulatory Activities of Flavonol Glycosides Isolated From Atriplex halimus L. Herb. (2016)
  • Author(s): Mona El-Aasr, Amal Kabbash, Kamilia A. Abo El-Seoud, Lamiaa A. Al-Madboly, Tsuyoshi Ikeda
  • Journal Title: J. Pharm. Sci. & Res. Volume: 8(10) Pages: 1159-1168
  • Peer Reviewed
• [Journal Article] Two new prenylflavonoids from Epimedii Herba and their inhibitory effects on advanced glycation end-products (2016)
  • Author(s): Nakashima, Keisuke; Miyashita, Hiroyuki; Yoshimitsu, Hitoshi; Fujiwara, Yukio; Nagai, Ryoji; Ikeda, Tsuyoshi
  • Journal Title: Journal of Natural Medicines Volume Volume: 70 (2) Issue: 2 Pages: 290-295
  • DOI: 10.1007/s11418-015-0962-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Two new bicyclic sulfoxides from Welsh onion (2016)
  • Author(s): Nohara, Toshihiro; Fujiwara, Yukio; Ikeda, Tsuyoshi; Murakami, Kotaro; Ono, Masateru; El-Aasr, Mona; Nakano, Daisuke; Kinjo, Junei
  • Journal Title: Journal of Natural Medicines Volume Volume: 70 (2) Issue: 2 Pages: 260-265
  • DOI: 10.1007/s11418-015-0947-z
  • NAID: 40020758269
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Soyasapogenols contained in soybeans suppress tumour progression by regulating macrophage differentiation into the protumoural phenotype (2015)
  • Author(s): Fujiwara, Yukio; Shiraishi, Daisuke; Yoshitomi, Makiko; Ikeda, Tsuyoshi; Mizuta, Hiroshi; Takeya, Motohiro; Komohara, Yoshihiro
  • Journal Title: Journal of Functional Foods Volume: 19 A Pages: 594-605
  • DOI: 10.1016/j.jff.2015.09.055
  • Peer Reviewed / Open Access
• [Journal Article] Saponins, Esculeosides B-1 and B-2, in Tomato Juice and Sapogenol, Esculeogenin B₁ (2015)
  • Author(s): Nohara, Toshihiro; Fujiwara, Yukio; Zhou, Jian-Rong; Urata, Jun; Ikeda, Tsuyoshi; Murakami, Kotaro; El-Aasr, Mona; Ono, Masateru
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 63 Issue: 10 Pages: 848-850
  • DOI: 10.1248/cpb.c15-00449
  • NAID: 130005100922
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of HSP70 inducing activity in Arnica montana extract and purification and characterization of HSP70 inducers (2015)
  • Author(s): Usui, Keiko; Ikeda, Tsuyoshi; Horibe, Yuumi; Nakao, Mitsuyoshi; Hoshino, Tatsuya; Mizushima, Tohru
  • Journal Title: Journal of Dermatological Science Volume: 78 Issue: 1 Pages: 67-75
  • DOI: 10.1016/j.jdermsci.2015.01.014
  • Peer Reviewed
• [Journal Article] A new hemiterpene glycoside from the ripe tomatoes (2015)
  • Author(s): M. Ono, S. Yasuda, Y. Shiono, C. Furusawa, S. Inaba, T. Tanaka, T. Ikeda, T. Nohara
  • Journal Title: Nat. Prod. Res. Volume: 29 Issue: 3 Pages: 262-267
  • DOI: 10.1080/14786419.2014.974053
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 終末糖化生成物の生成を阻害する天然薬物の探索研究ーローズレッドについてー (2017)
  • Author(s): 池田 剛、中嶋圭介、中村海里、野津原仙子、増田優姫子、 宮下裕幸、吉満 斉、藤原章雄、永井竜児
  • Organizer: 日本薬学会第137年会（仙台）
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2017-03-26
• [Presentation] 終末糖化生成物の生成を抑制する天然有機化合物の探索 (2016)
  • Author(s): 中嶋圭輔、宮下裕幸、吉満 斉、藤原章雄、永井竜児、池田 剛
  • Organizer: 日本薬学会第１３６年会（神奈川）
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-03-28
• [Presentation] Prenylated Flavonoids from Epimedii Herba Inhibits the Formation of Advanced Glycation End-products (2015)
  • Author(s): Tsuyoshi Ikeda
  • Organizer: International Conference on Conservation of Biodiversity and Sustainable Use of Tropical and Subtropical Plants
  • Place of Presentation: Guilin, China
  • Year and Date: 2015-11-02
  • Int'l Joint Research / Invited
• [Presentation] プレニル誘導体のAGEs生成阻害活性の検討 (2015)
  • Author(s): 中嶋圭輔、宮下裕幸、吉満 斉、藤原章雄、永井竜児、池田 剛
  • Organizer: 日本生薬学会第６２年会（岐阜）
  • Place of Presentation: 長良川国際センター（岐阜県岐阜市）
  • Year and Date: 2015-09-11
• [Presentation] イカリソウ由来のプレニルフラボノイド類のAGEs生成阻害活性の検討 (2015)
  • Author(s): 中嶋圭介、宮下裕幸、吉満 斉、藤原章雄、永井竜児、池田 剛
  • Organizer: 日本薬学会第135年会（神戸）
  • Place of Presentation: デザイン・クリエイティブセンター神戸（兵庫県、神戸市）
  • Year and Date: 2015-03-27
• [Presentation] イカリソウに含まれるAGEs生成阻害成分の探索研究 (2014)
  • Author(s): 中嶋圭介、宮下裕幸、吉満 斉、藤原章雄、永井竜児、池田 剛
  • Organizer: 第 24 回日本メイラード学会 年会（熊本）
  • Place of Presentation: 熊本市国際交流会館（熊本県、熊本市）
  • Year and Date: 2014-11-07
• [Presentation] イカリソウ由来のAGEs生成阻害活性プレニルフラボノイドの光学分割に関する研究 (2014)
  • Author(s): 中嶋圭介、宮下裕幸、吉満 斉、藤原章雄、永井竜児、池田 剛
  • Organizer: 日本生薬学会 第61回年会（福岡）
  • Place of Presentation: 福岡大学薬学部（福岡県、福岡市）
  • Year and Date: 2014-09-14
• [Presentation] イカリソウの終末糖化産物（AGEs）生成抑制成分について (2014)
  • Author(s): 中嶋圭介、宮下裕幸、吉満 斉、藤原章雄、永井竜児、池田 剛
  • Organizer: 生薬若手懇話会 第12回勉強会（佐世保）
  • Place of Presentation: 長崎国際大学薬学部（長崎県、佐世保市）
  • Year and Date: 2014-08-16
• [Book] Studies in Natural Products Chemistry (2014)
  • Author(s): Hirata, Tetsuya; Ikeda, Tsuyoshi; Fujikawa, Takahiko; Nishibe, Sansei
  • Total Pages: 35
  • Publisher: Elsevier B.V.