Biological activities and drug development of natural compounds with bone-resorbing and bone-forming properties during bone metabolism

• Project/Area Number: 26293024
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Chubu University
• Principal Investigator: WOO Je-Tae 中部大学, 応用生物学部, 教授 (20272693)
• Co-Investigator(Kenkyū-buntansha): 大西 素子 中部大学, 応用生物学部, 教授 (00312653) ; 車 炳允 中部大学, 生物機能開発研究所, 准教授 (00410663) ; 中川 大 中部大学, 応用生物学部, 講師 (40397039) ; 林 宣宏 東京工業大学, 生命理工学研究科, 准教授 (80267955)
• Co-Investigator(Renkei-kenkyūsha): TEI Yuichi 東京大学, 大学院工学系研究科, 教授 (30345053) ; OTA Masato 日本女子大学, 家政学部, 准教授 (70313228)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000); Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: 骨代謝 / 骨吸収抑制剤 / 骨形成促進剤 / 天然化合物 / 骨吸収 / 骨形成 / 破骨細胞 / 骨芽細胞 / 天然活性物質

Outline of Final Research Achievements

To elucidate the effect and mechanism of natural compounds which have both anti-resorptive action and anabolic action in bone metabolism, the following studies in vitro and in vivo were performed. It is demonstrated that honokiol might promote osteoblast differentiation throgh retinoid X receptor and sonic hedgehog pathway. The in vivo study revealed that honokiol suppresses bone loss in ovariectomized and RANKL-treated osteoporosis model mice. We also found that Nitensidine A from Pterogynine Nitens and Epimagnolin A from Magnolia Flower interact with ABCB1.

Research Products

• [Journal Article] Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity. (2017)
  • Author(s): Kim YJ, Choi MS, Woo JT, Jeong MJ, Kim SR, Jung UJ.
  • Journal Title: Mol Nutr Food Res Volume: 印刷中 Issue: 8
  • DOI: 10.1002/mnfr.201600889
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Biopiracy of natural products and good bioprospecting practice (2016)
  • Author(s): Efferth T, Banerjee M, Paul NW, Abdelfatah S,Khalid HE, Kuete V, Lee IS, Liu L, Midiwo J, Mora R, Nakagawa H, Ngassapa O, Noysang C, Omosa LK, Roland FH, Shahat AA, Saab A, Saeed EM, Shan L, Titinchi SJ
  • Journal Title: Phytomedicine Volume: 23 Issue: 2 Pages: 166-173
  • DOI: 10.1016/j.phymed.2015.12.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Honokiol, magnolol, and a combination of both compounds improve glucose metabolism in high-fat diet-induced obese mice (2015)
  • Author(s): Lee YS, Choi SS,Yonezawa T, Teruya T, Woo JT, Kim HJ, Cha BY
  • Journal Title: Food Science and Biotechnology Volume: 24 Pages: 1467-1474
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Hyperpigmentation mechanism of methyl 3,5-di-caffeoylquinate through activation of p38 and MITF induction of tyrosinase. (2015)
  • Author(s): Kim HJ, Kim JS, Woo JT, Lee IS, Cha BY.
  • Journal Title: Acta Biochim Biophys Sin Volume: 47 Issue: 7 Pages: 548-556
  • DOI: 10.1093/abbs/gmv040
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Nitensidine A, a guanidine alkaloid from Pterogyne nitens, induces osteoclastic cell death. (2015)
  • Author(s): Tajima Y, Muras H, Satake K, Mitani Y, Regasini LO, Bolzani Vda S, Efferth T, Nakagawa H,
  • Journal Title: Cytotechnology. 585-592. Volume: 67 Issue: 4 Pages: 585-592
  • DOI: 10.1007/s10616-013-9590-2
  • Peer Reviewed
• [Journal Article] Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens. (2015)
  • Author(s): Satake K, Tsukamoto M, Mitani Y, Regasini LO, Bolzani Vda S, Efferth T, Nakagawa H
  • Journal Title: Biomed Mater Eng Volume: 25 Issue: 3 Pages: 249-256
  • DOI: 10.3233/bme-151282
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rosmarinic acid exerts an anti-osteoporotic effect in the RANKL-induced mouse model of bone loss by promotion of osteoblastic differentiation and inhibition of osteoclastic differentiation. (2014)
  • Author(s): Lee JW, Asai M, Jeon SK, Iimura T, Yonezawa T, Cha BY, Woo JT, Yamaguchi A
  • Journal Title: Mol Nutr Food Res Volume: 59 Issue: 3 Pages: 386-400
  • DOI: 10.1002/mnfr.201400164
  • Peer Reviewed / Open Access
• [Presentation] ノビレチン高純度製法と多様な生理機能 (2017)
  • Author(s): 禹 済泰
  • Organizer: 日本動物細胞工学会
  • Place of Presentation: 総合コミュニティセンター（愛媛県松山）
  • Year and Date: 2017-07-20
  • Invited
• [Presentation] シークヮーサーからノビレチンの高純度粉末製法と多様な生理機能 (2017)
  • Author(s): 禹 済泰
  • Organizer: 日本栄養食糧学会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾）
  • Year and Date: 2017-05-19
  • Invited
• [Presentation] 抗マラリア薬Artsunate類による破骨細胞傷害作用機構の解析 (2017)
  • Author(s): 古川沙織, 丹羽悠菜, 柳瀬亜美, 中川大
  • Organizer: 137年会日本薬学会
  • Place of Presentation: 仙台国際センター（宮城県仙台）
  • Year and Date: 2017-03-24
• [Presentation] 卵巣摘出・更年期障害モデルマウスにおけるネポジンの糖・脂質代謝改善作用 (2016)
  • Author(s): 渡辺 章夫、丹羽 悠菜、森 美里、芝田 祐輔
  • Organizer: 第14回日本機能性食品医用学会総会
  • Place of Presentation: 順天堂大学（東京都東京）
  • Year and Date: 2016-12-10
• [Presentation] シークヮーサー由来ノビレチンの高含量抽出法確立と排尿障害改善効果 (2016)
  • Author(s): 禹 済泰、菅谷公男、伊藤由彦、山田静雄
  • Organizer: 第14回日本機能性食品医用学会総会
  • Place of Presentation: 順天堂大学（東京都東京）
  • Year and Date: 2016-12-10
  • Invited
• [Presentation] Effect of cinnamic acid derivatives from Brazilian green propolis on 3T3-L1 cells and RAW264.7 cells. (2016)
  • Author(s): Yusuke Deguchi, Akio Watanabe, Jairo Kenupp Bastos, Byung-Yoon Cha, Takayuki Yonezawa, and Je-Tae Woo
  • Organizer: 第3回 薬食国際カンファレンス
  • Place of Presentation: 日本平ホテル（静岡県静岡）
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] Melanogenic effect of 3-pyridinol isolated from coffee silver-skin on B16 melanoma. (2016)
  • Author(s): Akio Watanabe, Takayuki Yonezawa, Je-Tae Woo, Kiyotaka Nakagawa, Takashi Mishima, and Masatoshi Watai.
  • Organizer: 第3回 薬食国際カンファレンス
  • Place of Presentation: 日本平ホテル（静岡県静岡）
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] Immune modulating effect of extracts from Curucuma aromatica. (2016)
  • Author(s): Mizuki Goto, Akio Watanabe, Takayuki Yonezawa, Je-Tae Woo.
  • Organizer: 第3回 薬食国際カンファレンス
  • Place of Presentation: 日本平ホテル（静岡県静岡）
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] Effects of nepodin isolated from of Rumex japonicus in ovariectomized ddY mice. (2016)
  • Author(s): Ryuzo kozuka, Akio Watanabe, Takayuki Yonezawa, Je-Tae Woo.
  • Organizer: 第3回 薬食国際カンファレンス
  • Place of Presentation: 日本平ホテル（静岡県静岡）
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] Inhibitory Effects of Toddaculin Derived from Toddalia asiatica on Melanogenesis in B16 Melanoma Cells and 3D Human Skin Model. (2016)
  • Author(s): Akio Watanabe, Julia Ota, Takayuki Yonezawa, Je-Tae Woo,
  • Organizer: 第3回 薬食国際カンファレンス
  • Place of Presentation: 日本平ホテル（静岡県静岡）
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] Baccharin, Artepillin C, and Drupanin enhance adipocyte differentiation in 3T3-L1 cells (2016)
  • Author(s): Je-Tae Woo, Yusuke Deguch1, Akio Watanabe, Jairo Kenupp Bastos, Maria Palmira Daflon Gremião, Franciane Marquele de Oliveira, Andresa Aparecida Berretta, Byung-Yoon Cha, Takayuki Yonezawa
  • Organizer: Propolis Conference 2016
  • Place of Presentation: Glasgow, UK
  • Year and Date: 2016-06-17
  • Int'l Joint Research
• [Presentation] Epimagnolin, a tetrahydrofurofuranoid lignan from Magnolia sp., reverses ABCB1-mediated multidrug resistance. (2016)
  • Author(s): Nakagawa H, Mitani Y, Satake K, Tsukamoto M, Teruy T, Cha BY, Woo JT
  • Organizer: The 6th Special Meeting on ABC Proteins - ABC2016: From Multidrug Resistance
  • Place of Presentation: Innsbruck（オーストリア）
  • Year and Date: 2016-03-05
  • Int'l Joint Research
• [Presentation] Effect of a neolignan compound on bone-periodontal tissue formation (2015)
  • Author(s): Woo JT, Ohta M, Lee JW, Nakagawa H, Cha BY,Yonezawa T
  • Organizer: 2nd International Conference of Traditional and Complementary Medicine on Health
  • Place of Presentation: Taipei（台湾）
  • Year and Date: 2015-10-24
  • Int'l Joint Research
• [Presentation] Predicted crucial amino acid residues for substrate recognition by human ABCB1:in vitro analysis-based calculation using novel substrates for human ABCB1 from Pterogyne nitens and Magnolia sp. (2015)
  • Author(s): Nakagawa H, Satake K, Tsukamoto M, Toyoda Y, Kadioglu O, Regasini LO, Bolzani Vda S, Ishikawa T, T Fricker G, Efferth T
  • Organizer: Gordon Research Conference on Multi-Drug Efflux Systems.
  • Place of Presentation: Lucca（イタリア）
  • Year and Date: 2015-04-26
  • Int'l Joint Research