天然物医薬品の日独双方向国際展開に資する薬用植物の化学的研究

• Project/Area Number: 15F15108
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 外国
• Research Field: Natural medicines
• Research Institution: National Institute of Health Sciences
• Principal Investigator: 袴塚 高志 国立医薬品食品衛生研究所, 生薬部, 部長 (60221488)
• Co-Investigator(Kenkyū-buntansha): KUCHTA KENNY 国立医薬品食品衛生研究所, 生薬部, 外国人特別研究員
• Project Period (FY): 2015-04-24 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,300,000 (Direct Cost: ¥2,300,000); Fiscal Year 2016: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2015: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: 益母草 / メタボリックシンドローム / オリーブ

Outline of Annual Research Achievements

益母草は シソ科のメハジキ（Leonurus japonicus）を基原とし、産後の止血、月経不順、めまい、腹痛、急・慢性腎炎水腫など に適用される伝承薬であり、ヨーロッパでも近縁のマザーワートが婦人薬として利用されている。日本薬局方にはヤクモソウ（益母草）が収載され、欧州薬局方に同属植物のLeonurus cardiacaが収載されている。一方、オリーブは果実より絞った油がオリブ油として日本薬局方にも収載されているが、 その葉の利用方法は日欧で異なっている。オリーブの葉は、日本の食薬区分では「医薬品的効能効果を標榜しない限り食品と認められる成分本質（原材料）リスト」に区分され、日本では食品として利用されている。
クフタ氏は、日本とヨーロッパの両方で使用されているLeonurus属植物の植物化学研究を進めた。Leonurus属植物の抗不整脈作用を有する天然産物を同定するため、Leonurus japonicus及びLeonurus cardiacaより17種類の成分を単離した。ここでは、当研究所におけるLC/MS及びNMRを活用して活性化合物の構造解析が行われた。日欧双方の局方に収載されるLeonurus属植物において、それぞれの特徴的な化合物が含有されていた。さらに、PPARリガンド結合部位とGAL4結合部位を連結し、その下流にルシフェラーゼレポーター遺伝子を接続した発現ベクター系を用い、PPARβ/δ系に対する効果を評価し、主要な寄与因子として7R-クロロ-6-デスオキシ - ハルパジドを同定した。これらの結果は、第63回国際会議および薬用植物および自然産物研究協会（GA2015）の年次総会で発表された。一方、Olea europaeaのエキスについては、PPARα,β/σ及びγのいずれに関しても影響を及ぼさなかった。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Traditionelle Japanische Medizin-Kampo (Teil 5) Regulatorische Rahmenbedingungen fur Arzneimittel der Kampo- Medizin sowie verwandte phytotherapeutische Praparate in Japan. (2017)
  • Author(s): Kuchta K, Rausch H
  • Journal Title: Z Phytother Volume: 38 Pages: 24-26
  • Peer Reviewed
• [Journal Article] Celastrol, an active constituent of the TCM plant Tripterygium wilfordii Hook.F., inhibits prostate cancer bone metastasis. (2017)
  • Author(s): Kuchta K, Xiang Y, Huang S, Tang Y, Peng X, Wang X, Zhu Y, Li J, Xu J, Lin Z, Pan T
  • Journal Title: Prostate Cancer Prostatic Dis. Volume: 20(2) Issue: 2 Pages: 156-164
  • DOI: 10.1038/pcan.2016.61
  • Peer Reviewed
• [Journal Article] Identiofication of Cardioactive Leonurus and Leonotis Drug by Quantitative HPLC Determination and HPTLC Detection of Phenolic Marker Constituents. (2016)
  • Author(s): Kuchta K, Ortwein J, Calis I, Volk RB, Rauwald HW
  • Journal Title: Natural Product Communications Volume: 11(8) Pages: 1129-1133
  • Peer Reviewed
• [Journal Article] Curcumin, the main active constituent of turmeric (Curcuma longa L.), induces apoptosis in hepatic stellate cells by modulating the abundance of apoptosis-related growth factors. (2015)
  • Author(s): He YJ, Kuchta K, Lv X, Lin Y, Ye GR, Liu XY, Song HD, Wang LX, Kobayashi Y, Shu JC
  • Journal Title: Z Naturforsch C Volume: 70 Issue: 11-12 Pages: 281-285
  • DOI: 10.1515/znc-2015-4143
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] German Kava Ban Lifted by Court: The Alleged Hepatotoxicity of Kava (Piper methysticum) as a Case of Ill-Defined Herbal Drug Identity, Lacking Quality Control, and Misguided Regulatory Politics (2015)
  • Author(s): Kuchta K, Schmidt M, Nahrstedt A
  • Journal Title: Planta Med Volume: 81 Issue: 18 Pages: 1647-1653
  • DOI: 10.1055/s-0035-1558295
  • Peer Reviewed
• [Journal Article] GABAA Receptor Binding Assays of Standardized Leonurus cardiaca and Leonurus japonicus Extracts as Well as Their Isolated Constituents (2015)
  • Author(s): Rauwald HW, Savtschenko A, Merten A, Rusch C, Appel K, Kuchta K
  • Journal Title: Planta Med Volume: 81 Issue: 12/13 Pages: 1103-1110
  • DOI: 10.1055/s-0035-1546234
  • Peer Reviewed
• [Journal Article] Effects of bergamot (Citrus bergamia (Risso) Wright & Arn.) essential oil aromatherapy on mood states, parasympathetic nervous system activity, and salivary cortisol levels in 41 healthy females (2015)
  • Author(s): Watanabe E, Kuchta K, Kimura M, Rauwald HW, Kamei T, Imanishi J
  • Journal Title: Forsch Komplementmed Volume: 22 Issue: 1 Pages: 43-49
  • DOI: 10.1159/000380989
  • Peer Reviewed / Int'l Joint Research
• [Presentation] A New Phytotherapeutic Preparation Based on Traditional Japanese Kampo Medicine Developed and Optimized for the Treatment of Neuronal Disorders. (2016)
  • Author(s): Kuchta K
  • Organizer: International Symposium on Natural Products for the Future 2016
  • Place of Presentation: Tokushima, Japan
  • Year and Date: 2016-09-01
  • Int'l Joint Research
• [Presentation] Quality control of saffron (Crocus sativus L.) via a novel HPLC method. (2016)
  • Author(s): Kuchta K, Jin HH, Wang RW, He HH, Fang L, Yao JB
  • Organizer: 9th Joint Meeting of AFERP, ASP, GA, JSP, PSE & SIF
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2016-07-24
  • Int'l Joint Research
• [Presentation] Development and optimization of a phytotherapeutic preparation based on traditional Japanese Kampo medicine against gastrointestinal sidorders. (2016)
  • Author(s): Frank L, Weimer K, Cameron S, Kuchta K, Rausch H
  • Organizer: 9th Joint Meeting of AFERP, ASP, GA, JSP, PSE & SIF
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2016-07-24
  • Int'l Joint Research
• [Presentation] Development and optimization of a phytotherapeutic preparation based on traditional Japanese Kampo medicine against neuronal disorders. (2016)
  • Author(s): Weimer K, Frank L, Cameron S, Kuchta K, Rausch H
  • Organizer: 9th Joint Meeting of AFERP, ASP, GA, JSP, PSE & SIF
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2016-07-24
  • Int'l Joint Research
• [Presentation] Isolation and profilig of coumarin glycosides from the antihyperuricemic ethanol extract of mulberry (Morus alba L.) twings (Chin. Ph.) (2016)
  • Author(s): Kuchta K, He HH, Yao JB, Ai W, Wang JF, Wu J, Hu JN, Wang RW
  • Organizer: 9th Joint Meeting of AFERP, ASP, GA, JSP, PSE & SIF
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2016-07-24
  • Int'l Joint Research
• [Presentation] The neuroprotective activity of a proanthocyanidin enriched Gingko biloba L. leaves extract in vitro and in vivo. (2016)
  • Author(s): Kuchta K, Qiao HX, Huang HB, Fang L, Chen Y, Wang RW
  • Organizer: 9th Joint Meeting of AFERP, ASP, GA, JSP, PSE & SIF
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2016-07-24
  • Int'l Joint Research
• [Presentation] Neuroprotective activity in vivo and HPLC determination of 6-hydroxykynurenic acid (6-HKA), an active constituent of Ginkgo biloba L. leaves extract. (2016)
  • Author(s): Kuchta K, Qiao HX, Wang RW, Huang HB, Jin ZM, Chen Y
  • Organizer: 9th Joint Meeting of AFERP, ASP, GA, JSP, PSE & SIF
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2016-07-24
  • Int'l Joint Research
• [Presentation] Seasonal variations of the contents of genistein and 6-HKA in Ginkgo biloba L. leaves from different regions of China. (2016)
  • Author(s): Kuchta K, Yao JB, Du X, Jin HH, Fang L, Min H, Qiao HX, Wang RW
  • Organizer: 9th Joint Meeting of AFERP, ASP, GA, JSP, PSE & SIF
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2016-07-24
  • Int'l Joint Research
• [Presentation] Entwicklung und Optimierung eines Phytopharmakons aus der japanischen Kampo-Tradition im Anwendungsbereich bei neuronalen Storungen. (2016)
  • Author(s): Weimer K, Frank L, Cameron S, Kuchta K, Rausch H
  • Organizer: Phytotherapie 2016
  • Place of Presentation: Bonn, Germany
  • Year and Date: 2016-07-02
• [Presentation] Entwicklung und Optimierung eines Phytopharmakons aus der japanischen Kampo-Tradition im Anwendungsbereich "Gastrointestinaltrakt.". (2016)
  • Author(s): Frank L, Weimer K, Cameron S, Kuchta K, Rausch H
  • Organizer: Phytotherapie 2016
  • Place of Presentation: Bonn, Germany
  • Year and Date: 2016-07-02
• [Presentation] Neuentwicklung einer HPLC-Methode zur Qualitatskontrolle von Safran (Crocus sativus L.). (2016)
  • Author(s): Kuchta K, Jin HH, Wang RW, He HH, Fang L, Yao JB
  • Organizer: Phytotherapie 2016
  • Place of Presentation: Bonn, Germany
  • Year and Date: 2016-07-02
• [Presentation] Entwicklung und Optimierung eines Phytopharmakons aus der japanischen Kampo-Tradition im Anwendungsbereich bei neuronalen Storungen. (2016)
  • Author(s): Kuchta K
  • Organizer: Phytotherapie-Kongress der Gesellschaft fur Phytotherapie.
  • Place of Presentation: Bonn, Germany
  • Year and Date: 2016-06-02
• [Presentation] 欧州における漢方について (2016)
  • Author(s): ケニー クフタ
  • Organizer: 漢方産業化推進研究会 平成28年度第１回研究会
  • Place of Presentation: 東京
  • Year and Date: 2016-05-11
  • Invited
• [Presentation] Phytotherapy in Europe (2016)
  • Author(s): Kuchta K
  • Organizer: 18th International Congress of Oriental Medicine（ICOM)
  • Place of Presentation: Ginowan, Okinawa, Japan
  • Year and Date: 2016-04-15
  • Invited
• [Presentation] Effects of herbs of the genus Leonurus and 17 of their isolated constituents on PPARα, β/δ, and γ in a luciferase reporter gene assay. (2015)
  • Author(s): Kuchta K
  • Organizer: 日本生薬学会第62回年会
  • Place of Presentation: 岐阜市
  • Year and Date: 2015-09-12
• [Presentation] Screening of 22 Medicinal Plant Extracts with an in vitro Luciferase Reporter Gene Assay for Effects on the Metabolic Syndrome Related Targets PPARα, β/δ, and γ - Mainly Concentrating on the Genus Leonurus and 17 of its Isolated Constituents. (2015)
  • Author(s): Kuchta K
  • Organizer: ISPSA2015, the Inaugural Symposium of the Phytochemical Society of Asia
  • Place of Presentation: 徳島市
  • Year and Date: 2015-09-01
  • Int'l Joint Research
• [Presentation] Effects of medicinal plants of the genus Leonurus and seventeen of their isolated constituents on the activity of PPARα, β/δ, and γ in an in vitro luciferase reporter gene assay. (2015)
  • Author(s): Kuchta K, Matsuura N, Rauwald HW, Rusch C, Shoyama Y, Iinuma M
  • Organizer: XIXth International Congress PHYTOPHARM
  • Place of Presentation: Bonn (Germany)
  • Year and Date: 2015-07-23
  • Int'l Joint Research
• [Presentation] Screening of 19 traditional Mexican medicinal plants for effects on the metabolic syndrome related targets PPARα, β/δ, and γ in an in vitro luciferase reporter gene assay (2015)
  • Author(s): Kuchta K, Matsuura N, Rauwald HW, Quintanilla-Licea R, Iinuma M
  • Organizer: XIXth International Congress PHYTOPHARM
  • Place of Presentation: Bonn (Germany)
  • Year and Date: 2015-07-23
  • Int'l Joint Research
• [Presentation] Curcumin induces apoptosis in hepatic stellate cells via inhibition of the MyD88 pathway. (2015)
  • Author(s): Shu JC, Kuchta K, He YJ, Deng YM, Lin Y, Ye GR, Lv X, Liu XY, Kobayashi Y
  • Organizer: XIXth International Congress PHYTOPHARM
  • Place of Presentation: Bonn (Germany)
  • Year and Date: 2015-07-22
  • Int'l Joint Research
• [Presentation] Celastrol, an active constituent of the TCM plant Tripterygium wilfordii, inhibits prostate cancer bone metastasis. (2015)
  • Author(s): Kuchta K, Xiang Y, Huang S, Tang Y, Peng X, Wang X, Zhu Y, Li J, Xu J, Lin Z, Pan T
  • Organizer: XIXth International Congress PHYTOPHARM
  • Place of Presentation: Bonn (Germany)
  • Year and Date: 2015-07-22
  • Int'l Joint Research
• [Presentation] How to receive regulatory approval in Japan for Western Herbal Medicinal Products (WHMP) (2015)
  • Author(s): Kuchta K
  • Organizer: XIXth International Congress PHYTOPHARM
  • Place of Presentation: Bonn (Germany)
  • Year and Date: 2015-07-22
  • Int'l Joint Research
• [Presentation] Effects of Leonurus japonicus Houtt. and eight of its bioactive constituents on the activity of PPARα, β/δ, and γ in a newly developed in vitro luciferase reporter gene assay. (2015)
  • Author(s): Kuchta K
  • Organizer: International Symposium for Japanese Kampo Medicine
  • Place of Presentation: Vienna (Austria)
  • Year and Date: 2015-06-20
  • Int'l Joint Research
• [Presentation] Inhibition of Prostate Cancer Bone Metastasis by Celastrol, a Bioactive Constituent of Tripterygium wilfordii 雷公藤. (2015)
  • Author(s): Kuchta K
  • Organizer: 第2回日本健康促進医学会学術総会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-05-18
• [Book] Lehrbuch Phytotherapie 13th edition (2016)
  • Author(s): Fintelmann V, Weiss RF, Kuchta K
  • Total Pages: 440
  • Publisher: Haug