Therapeutic effect of natural compounds regulating macrophage activation on life style-diseases.

• Project/Area Number: 23790747
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: Kumamoto University
• Principal Investigator: FUJIWARA Yukio 熊本大学, 大学院・生命科学研究部, 助教 (70452886)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 代替医療 / マクロファージ / 天然化合物 / ガン

Research Abstract

It is well known that tumor-associated macrophages play an important role in cancer growth. In this study, we identified several natural compounds, such as corosolic acid and onionin which regulate macrophage activation. These compounds change M2 polarization to M1 polarization by inhibition of STAT3 activation in macrophages. Therefore, these compounds may be potentially new tool for tumor prevention and therapy.

Research Products

• [Journal Article] Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells (2013)
  • Author(s): Horlad Hasita, Fujiwara Yukio, Takemura Kenichi, Ohnishi Koji, Ikeda Tsuyoshi, Tsukamoto Hirotake, Mizuta Hiroshi, Nishimura Yasuharu, Takeya Motohiro, Komohara Yoshihiro
  • Journal Title: Mol. Nutri. Food Res Volume: 57 (6) Issue: 6 Pages: 1-9
  • DOI: 10.1002/mnfr.201200610
  • Peer Reviewed
• [Journal Article] Marked cardiomegaly in a patient with familial amyloidotic polyneuropathy after liver transplantation: a case study. (2013)
  • Author(s): Sakashita N et al
  • Journal Title: Pathology International Volume: in press Issue: 5 Pages: 306-312
  • DOI: 10.1111/j.1440-1827.2011.02652.x
  • Peer Reviewed
• [Journal Article] Role of Stat3 activation in cell-cell interaction between B-cell lymphoma and macrophages: the in vitro study. (2013)
  • Author(s): Bing Bai, Hasita Horlad, Yoichi Saito, Koji Ohnishi, Yukio Fujiwara, Motohiro Takeya, Yoshihiro Komohara.
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: in press
  • NAID: 10031194234
  • Peer Reviewed
• [Journal Article] Importance of direct macrophage-tumor cell interaction on progression of human glioma. (2012)
  • Author(s): Komohara Y, Horlad H, Ohnishi K, Fujiwara Y, Bai B, Nakagawa T, Suzu S, Nakamura H, Kuratsu J, Takeya M.
  • Journal Title: Cancer Sci Volume: 103(12) Issue: 12 Pages: 2165-72
  • DOI: 10.1111/cas.12015
  • Peer Reviewed
• [Journal Article] Glucagon-like peptide-1 (GLP-1) induces M2 polarization of human macrophages via STAT3 activation. (2012)
  • Author(s): Shiraishi D, Fujiwara Y, Komohara Y, Mizuta H, Takeya M.
  • Journal Title: Biochem Biophys Res Commun Volume: 425 Issue: 2 Pages: 304-308
  • DOI: 10.1016/j.bbrc.2012.07.086
  • Peer Reviewed
• [Journal Article] Garlicnins B(1), C(1), and D,from the fraction regulating macrophage activation of Allium sativum (2012)
  • Author(s): Nohara T, Fujiwara Y (7^th author), +7 authors
  • Journal Title: Chem Pharm Bull Volume: 60 Pages: 747-751
  • NAID: 130001852475
  • URL: https://www.jstage.jst.go.jp/article/cpb/60/6/60_c12-00125/_article
  • Peer Reviewed
• [Journal Article] Tomatidine, a Tomato Sapogenol, Ameliorates Hyperlipidemia and Atherosclerosis in ApoE-Deficient Mice by Inhibiting Acyl-CoA : cholesterol Acyl- transferase (ACAT) (2012)
  • Author(s): Fujiwara Yukio, Kiyota Naoko, Tsurushima Keiichiro, Yoshitomi Makiko, Horlad Hasita, Ikeda Tsuyoshi, Nohara Toshihiro, Takeya Motohiro, Nagai Ryoji
  • Journal Title: J. Agri. Food Chem Volume: 60 (10) Issue: 10 Pages: 2472-2479
  • DOI: 10.1021/jf204197r
  • Peer Reviewed
• [Journal Article] Dysregulation of dimethylargininedimethylaminohydrolase/asymmetric dimethylarginine pathway in rat type II diabetic nephropathy (2012)
  • Author(s): Miyoshi N
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 51 Issue: 2 Pages: 143-149
  • DOI: 10.3164/jcbn.11-33
  • NAID: 130004879298
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] A dipeptidylpeptidase-4 inhibitor,des-fluoro-sitagliptin, improvesendothelial function and reducesatherosclerotic lesion formation inapolipoprotein E-deficient mice (2012)
  • Author(s): Matsubara J, Sugiyama S, Sugamura K,Nakamura T, Fujiwara Y, Akiyama E,Kurokawa H, Nozaki T, Ohba K, Konishi M,Maeda H, Izumiya Y, Kaikita K, Sumida H,Jinnouchi H, Matsui K, Kim-Mitsuyama S,Takeya M, Ogawa H
  • Journal Title: J AmColl Cardiol Volume: 59(3) Issue: 3 Pages: 265-76
  • DOI: 10.1016/j.jacc.2011.07.053
  • Peer Reviewed
• [Journal Article] Garlicnins B(1), C(1), and D, from the fraction regulating macrophage activation of Allium sativum. (2012)
  • Author(s): Toshihiro Nohara , Yuka Kiyota, Toyonobu Sakamoto, Hideyuki Manabe, Masateru Ono, Tsuyoshi Ikeda, Yukio Fujiwara, Daisuke Nakano, Junei Kinjo.
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 60 Pages: 747-751
  • NAID: 130001852475
  • Peer Reviewed
• [Journal Article] Garlicnin A from the fraction regulating macrophage activation of Allium sativum (2011)
  • Author(s): El-Aasr M, Fujiwara Y (2^nd author), +9 authors
  • Journal Title: Chem Pharm Bull Volume: 59 Pages: 1340-1343
  • NAID: 130001274807
  • URL: https://www.jstage.jst.go.jp/article/cpb/59/11/59_11_1340/_article
  • Peer Reviewed
• [Journal Article] Oleanolic acid inhibits macrophage differentiation into the M2 phenotype and glioblastoma cell proliferation by suppressing the activation of STAT3 (2011)
  • Author(s): Fujiwara Y., Komohara Y., Kudo R., Tsurushima K., Ohnishi K., Ikeda T., Takeya M.,
  • Journal Title: Oncology Reports Volume: 26 Pages: 1533-1537
  • DOI: 10.3892/or.2011.1454
  • Peer Reviewed
• [Journal Article] N^?-(carboxymethyl)arginine Accumulates in Glycated Collagen and Klotho-deficient Mouse Skin (2011)
  • Author(s): Shimasaki S, Fujiwara Y (7^th author), +6 authors
  • Journal Title: Anti-Aging Medicin Volume: 8 Pages: 82-87
  • URL: http://www.anti-aging.gr.jp/english/pdf/2011/8(6)82-87.pdf
  • Peer Reviewed
• [Journal Article] Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204). (2011)
  • Author(s): Ohnishi K, Komohara Y, Fujiwara Y, Takemura K, Lei X, Nakagawa T, Sakashita N, Takeya M.
  • Journal Title: Biochem Biophys Res Commun Volume: 411 Issue: 3 Pages: 516-522
  • DOI: 10.1016/j.bbrc.2011.06.161
  • Peer Reviewed
• [Journal Article] Triterpenes Isolated from Zizyphus Jujuba Inhibit the Foam Cell Formation in Macrophages (2011)
  • Author(s): Y.Fujiwara, et al
  • Journal Title: J.Agric.Food Chem. Volume: 59 Issue: 9 Pages: 4544-4552
  • DOI: 10.1021/jf200193r
  • Peer Reviewed
• [Journal Article] Macrophage infiltration and its prognostic relevance in clear cell renal cell carcinoma. (2011)
  • Author(s): Komohara Y, Hasita H, Ohnishi K, Fujiwara Y, Suzu S, Eto M, Takeya M.
  • Journal Title: Cancer Sci Volume: 102 Issue: 7 Pages: 1424-1431
  • DOI: 10.1111/j.1349-7006.2011.01945.x
  • NAID: 10029295791
  • Peer Reviewed
• [Journal Article] atural compounds containing a catechol group enhance the formation of Nε-(carboxymethyl)lysine of the Maillard reaction. (2011)
  • Author(s): Fujiwara Y, Kiyota N, Tsurushima K, Yoshitomi M, Mera K, Sakashita N, Takeya M, Ikeda T, Araki T, Nohara T, Nagai R.
  • Journal Title: Free Radic Biol Med Volume: 50 Issue: 7 Pages: 883-891
  • DOI: 10.1016/j.freeradbiomed.2010.12.033
  • Peer Reviewed
• [Journal Article] Changes in Esculeoside A Content in Different Regions of the Tomato Fruit during Maturation and Heat Processing. (2011)
  • Author(s): Katsumata A, Fujiwara Y (7^th author), +6 authors
  • Journal Title: J Agric Food Chem Volume: 59 Issue: 8 Pages: 4104-4110
  • DOI: 10.1021/jf104025p
  • Peer Reviewed
• [Journal Article] Corosolic acid Inhibits Glioblastoma Cell Proliferation by Suppressing the Activation of STAT3 and NF-κB in Tumor Cells and Tumor-associated Macrophages. (2011)
  • Author(s): Fujiwara Y, Komohara Y, Ikeda T,Takeya M.
  • Journal Title: Cancer Sci Volume: 102 Issue: 1 Pages: 206-211
  • DOI: 10.1111/j.1349-7006.2010.01772.x
  • Peer Reviewed
• [Journal Article] Content variations of the tomatosaponin esculeoside A in various processedtomatoes. (2011)
  • Author(s): Manabe H, Fujiwara Y (5^th author), +5 authors
  • Journal Title: J Nat Med Volume: 65 Issue: 1 Pages: 176-179
  • DOI: 10.1007/s11418-010-0443-4
  • Peer Reviewed
• [Journal Article] Garlicnin A from the Fraction Regulating Macrophage Activation of <i>Allium sativum</i> (2011)
  • Author(s): Mona El-Aasr, Yukio Fujiwara, Motohiro Takeya, Masateru Ono, Daisuke Nakano, Masafumi Okawa, Junei Kinjo, Tsuyoshi Ikeda, Hiroyuki Miyashita, Hitoshi Yoshimitsu, Toshihiro Nohara
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 59 Issue: 11 Pages: 1340-1343
  • DOI: 10.1248/cpb.59.1340
  • NAID: 130001274807
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed
• [Journal Article] <i>N^&omega;</i>-(carboxymethyl)arginine Accumulates in Glycated Collagen and Klotho-deficient Mouse Skin (2011)
  • Author(s): Shimasaki S., et.al
  • Journal Title: ANTI-AGING MEDICINE Volume: 8 Issue: 6 Pages: 82-87
  • DOI: 10.3793/jaam.8.82
  • NAID: 130001290312
  • ISSN: 1882-2762
  • Peer Reviewed
• [Journal Article] The Tomato Saponin, Esculeoside A
  • Author(s): Nohara T, Fujiwara Y (4^thauthor), +8authors
  • Journal Title: J. Nat. Prod Volume: (in press)
  • URL: http://pubs.acs.org/doi/abs/10.1021/np100311t
  • Peer Reviewed
• [Presentation] 大豆含有成分のマクロファージ活性化制御を介した骨肉腫抑制作用の検討 (2013)
  • Author(s): 藤原章雄、Hasita Horlad、白石大偉輔、菰原義弘、池田剛、竹屋元裕
  • Organizer: 日本薬学会 第133 年会
  • Place of Presentation: パシフィコ横浜(横浜)
• [Presentation] Onionin A suppresses osteosarcoma development by inhibiting Stat3 activation in both macrophages and tumor cells. (2013)
  • Author(s): Yukio Fujiwara, Yoshihiro Komohara, Ohnishi Koji, Motohiro Takeya.
  • Organizer: EMBO Workshop
  • Place of Presentation: Centre d'Immunologie Marseille-Luminy, Marseille (France)
• [Presentation] 大豆含有成分のマクロファージ活性化制御を介した骨肉腫抑制作用の検討 (2013)
  • Author(s): 藤原章雄、Hasita Horlad、白石大偉輔、菰原義弘、池田剛、竹屋元裕
  • Organizer: 日本薬学会 第133年会
  • Place of Presentation: パシフィコ横浜（ 横浜）
• [Presentation] GLP-1 はマクロファージをM2 フェノタイプへ誘導する (2012)
  • Author(s): 藤原章雄、白石大偉輔、菰原義弘、水田博志、竹屋元裕
  • Organizer: 第85回 日本生化学会大会
  • Place of Presentation: マリンメッセ福岡(福岡)
• [Presentation] マクロファージの活性化を制御する天然化合物の探索研究 ～ガン免疫療法への応用を目指して～ (2012)
  • Author(s): 藤原章雄
  • Organizer: 日本生薬学会 第59回年会
  • Place of Presentation: かずさアカデミアパーク(千葉)
• [Presentation] Onionin A のマクロファージ活性化制御を介した腫瘍免疫賦活作用 (2012)
  • Author(s): 藤原章雄、白石大偉輔、Horlad Hasita、菰原義弘、工藤梨乃、野原稔弘、竹屋元裕
  • Organizer: 第52回 日本リンパ網内系学会総会
  • Place of Presentation: ホテル福島グリーンパレス(福島)
• [Presentation] マクロファージの活性化を制御する Corosolic acid の骨肉腫移植モデルマウスにおける効果の検討 (2012)
  • Author(s): 藤原章雄、Horlad Hasita 、菰原義弘、大西紘二、池田剛、竹屋元裕
  • Organizer: 第101回 日本病理学会総会
  • Place of Presentation: 京王プラザホテル(東京)
• [Presentation] Corosolic acid suppresses osteosarcoma development and lung metastasis by targeting STAT3 signaling pathway (2012)
  • Author(s): Yukio Fujiwara, Yoshihiro Komohara,Horlad Hasita, Koji Ohnishi, Kenichi Takemura, Tsuyoshi Ikeda, Motohiro Takeya
  • Organizer: The 11th Korean-Japanese lymphoreticular workshop
  • Place of Presentation: Seoul University(Korea)
• [Presentation] マクロファージの活性化を制御するCorosolic acidの骨肉腫移植モデルマウスにおける効果の検討 (2012)
  • Author(s): 藤原章雄、Horlad Hasita 、菰原義弘、大西紘二、池田剛、竹屋元裕
  • Organizer: 第101回 日本病理学会総会
  • Place of Presentation: 京王プラザホテル（ 東京）
• [Presentation] Onionin Aのマクロファージ活性化制御を介した腫瘍免疫賦活作用 (2012)
  • Author(s): 藤原章雄、白石大偉輔、Horlad Hasita、菰原義弘、工藤梨乃、野原稔弘、竹屋元裕
  • Organizer: 第52回 日本リンパ網内系学会総会
  • Place of Presentation: 福島ビューホテル（ 福島）
• [Presentation] マクロファージの活性化を制御する天然化合物の探索研究 ～ガン免疫療法への応用を目指して～ (2012)
  • Author(s): 藤原章雄
  • Organizer: 日本生薬学会 第59回年会
  • Place of Presentation: かずさアカデミアパーク（ 千葉）
  • Invited
• [Presentation] GLP-1 はマクロファージをM2フェノタイプへ誘導する (2012)
  • Author(s): 藤原章雄、白石大偉輔、 菰原義弘、水田博志、竹屋元裕
  • Organizer: 第85回 日本生化学会大会
  • Place of Presentation: 福岡国際会議場（ 福岡）
• [Presentation] Corosolic acid suppresses osteosarcoma development and lung metastasis by targeting STAT3 signaling pathway. (2012)
  • Author(s): Yukio Fujiwara, Yoshihiro Komohara, Horlad Hasita, Koji Ohnishi, Kenichi Takemura, Tsuyoshi Ikeda, Motohiro Takeya
  • Organizer: The 11th Korean-Japanese lymphoreticular workshop, January 27-29, 2012 (Seoul, Korea, Seoul University)
  • Place of Presentation: Seoul University（ソウル・韓国）
• [Presentation] CMA 生成を阻害する天然化合物の探索 (2011)
  • Author(s): 藤原章雄、吉冨万希子、池田剛、永井竜児、竹屋元裕
  • Organizer: 第21回 日本メイラード学会年会
  • Place of Presentation: サピアタワー(東京)
  • Year and Date: 2011-10-28
• [Presentation] タマネギ由来新規化合物 onionin A のマクロファージ活性化に対する作用の検討 (2011)
  • Author(s): 藤原章雄、工藤梨乃、菰原義弘、Horlad Hasita、大西紘二、野原稔弘、竹屋元裕
  • Organizer: 日本生薬学会 第58回年会
  • Place of Presentation: 昭和大学(東京)
• [Presentation] Onionin A のマクロファージ活性化制御を介したガン細胞増殖抑制作用 (2011)
  • Author(s): 藤原章雄、工藤梨乃、菰原義弘、Horlad Hasita 、大西紘二 、野原稔弘 、竹屋元裕
  • Organizer: 第84回 日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都)
• [Presentation] Corosolic acid,onionin A and garlicnin A Inhibit Tumor Cells Proliferation by Suppressing the Activation of STAT3 in Tumor Cells and Tumor-associated Macrophages (2011)
  • Author(s): Yukio Fujiwara, Yoshihiro Komohara,Rino Kudo, Tsuyoshi Ikeda, Toshihiro Nohara, Motohiro Takeya
  • Organizer: XI ASIAN CONGRESS OF NUTRITION 2011
  • Place of Presentation: Suntec Singapore International Convention and Exhibition Centre (Singapore)
• [Presentation] Corosolic acid のマクロファージ活性化制御を介した癌免疫賦活作用 (2011)
  • Author(s): 藤原章雄、菰原義弘、竹村健一、池田剛、竹屋元裕
  • Organizer: 第51回 日本リンパ網内系学会
  • Place of Presentation: 福岡国際会議場(福岡)
• [Presentation] Onionin A のマクロファージ活性化制御作用 (2011)
  • Author(s): 藤原章雄、工藤梨乃、菰原義弘、野原稔弘、坂下直実、竹屋元裕
  • Organizer: 第100回 日本病理学会総会
  • Place of Presentation: パシフィコ横浜 (神奈川)
• [Presentation] Corosolic acid Inhibits Glioblastoma Cell Proliferation by Suppressing the Activation of STAT3 and NF-κB in Tumor Cells and Tumor-associated Macrophages. (2011)
  • Author(s): Yukio Fujiwara, Yoshihiro Komohara, Tsuyoshi Ikeda, Motohiro Takeya
  • Organizer: 19th International Synposium on Molecular Cell Biology of Macrophages
  • Place of Presentation: ANA Gate Tower Hotel（大阪）
• [Presentation] Corosolic acid, onionin A and garlicnin A Inhibit Tumor Cells Proliferation by Suppressing the Activation of STAT3 in Tumor Cells and Tumor-associated Macrophages. (2011)
  • Author(s): Yukio Fujiwara, Yoshihiro Komohara, Rino Kudo, Tsuyoshi Ikeda, Toshihiro Nohara, Motohiro Takeya
  • Organizer: XI ASIAN CONGRESS OF NUTRITION 2011
  • Place of Presentation: The Suntec Singapore International Convention & Exhibition Centre（シンガポール）
• [Presentation] Onionin Aのマクロファージ活性化制御作用 (2011)
  • Author(s): 藤原章雄、工藤梨乃、菰原義弘、野原稔弘、坂下直実、竹屋元裕
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: パシフィコ横浜（神奈川）
• [Presentation] Corosolic acidのマクロファージ活性化制御を介した癌免疫賦活作用 (2011)
  • Author(s): 藤原章雄、菰原義弘、竹村健一、池田剛、竹屋元裕
  • Organizer: 第51回日本リンパ網内系学会
  • Place of Presentation: 福岡国際会議場（福岡）
• [Presentation] Onionin Aのマクロファージ活性化制御を介したガン細胞増殖抑制作用 (2011)
  • Author(s): 藤原章雄、工藤梨乃、菰原義弘、Horlad Hasita、大西紘二、野原稔弘、竹屋元裕
  • Organizer: 第84回日本生化学会大会 平成23年9月21-24日
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] タマネギ由来新規化合物 onionin A のマクロファージ活性化に対する作用の検討 (2011)
  • Author(s): 藤原章雄、工藤梨乃、菰原義弘、Horlad Hasita、大西紘二、野原稔弘、竹屋元裕
  • Organizer: 日本生薬学会 第58回年会
  • Place of Presentation: 昭和大学（東京）
• [Presentation] CMA生成を阻害する天然化合物の探索 (2011)
  • Author(s): 藤原章雄、吉冨万希子、池田剛、永井竜児、竹屋元裕
  • Organizer: 第21回日本メイラード学会年会
  • Place of Presentation: サピアタワー（東京）
• [Remarks] 研究室ホームページ
  • URL: http://www.medic.kumamoto-u.ac.jp/dept/patho2/patho2.html
• [Remarks] 熊本大学大学院生命科学研究部細胞病理学分野ホームページ
  • URL: http://www.medic.kumamoto-u.ac.jp/dept/patho2/patho2.html
• [Remarks]
  • URL: http://srv02.medic.kumamoto-u.ac.jp/dept/patho2/patho2.html