研究成果報告書

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2 Arterioscler Thromb Vasc Biol., 27, (2007) J. Agri. Food Chem., 59, (2011) Bioorg. Med. Chem. Lett., 21, (2011) Advanced glycation end products (AGEs) AGEs AGEs AGEs HbA1c N AGEs 1,2-eminal A G E Advanced Glycation End products 1) 2) 3) 4) AGE CMLCMA CMLCMA ELISA AGEs Nagai R., Ikeda T.,et al., Ann. N.Y. Acad. Sci., 1126, (2008) 54 CML CMA 14 CML 6 CMA CML CMLCMA Astragaloside V Ikeda T.,et al., J. Agri. Food Chem., 57, (2009)Luteolin CML CMA Batta B., et al., Curr. Med. Chem., 12, (2005) AGEs Disease processes AGEs AGEs 30 AGEs lysine CMLN ε -(carboxymethyl) lysine arginine CMA N - (carboxymethyl) argininecml AGEs CML RAGE (receptor for AGE) CMA AGEs CMA AGEs CMLCMA AGEs AGEs CML CMA ELISA Luteolin

3 2,3 HPLC MCI gel CHP-20P AGEs 80% 100% Sephadex LH HPLC NMR AGEs CMLCMA CMLCMA (30 mm) (2 mg/ml) DMSO (100M) 37 C 7 CML Mouse monoclonal anti-cml antibody (6D12)CMA Mouse monoclonal anti-cma antibody (3F5) CML, CMA ELISA AGEs Pyridoxamine Luteolin ELISA 96 well 10 g protein/ml 2 Blocking buffer 1 1 HRP-goat anti-mouse IgG nm Ribose + Gelatin (30 mm) (2 mg/ml) in 10 mm PBS (CML) in 100 mm Na-PB (CMA) 35 CML, CMA ELISA CML, CMA glycosides aglycones Incubation 37ºC 7 days Sample CML: 1 µm glycosides aglycones 2 1 ELISA AGEs CMA: 10 µm CML, CMA

4 Epimedokoreanin B (EKB) Epimedonin E, G, H B A 8B 5 A 5 gallic acid, pyrogallol, chlorogenic acid) EKB EK-B (8) Luteolin Chlorogenic acid Pyrogallol Gallic acid 8 A C 5 B Epimedokoreanin B (8) Epimedonin E (21) Epimedonin G (22) Epimedonin H (24) (EK-B) CML: 1.0 µm (meansd, n=3) CMA: 10 µm (meansd, n=3) Epimedonin G, H Epimedonin G1, G2, H1, H2 S R CML, CMA (meansd, n=3) (meansd, n=3) Artepillin C, Baccharin, Drupanin Artepillin C Baccharin Drupanin Epimedonin G1 (22-1) Epimedonin G2 (22-2) Epimedonin H1 (24-1) Epimedonin H2 (24-2) CML: 1.0 µm (meansd, n=3) CMA: 10 µm (meansd, n=3) EKB (meansd, n=3) (meansd, n=3) (meansd, n=3) (meansd, n=3) OMe OH OSugar Epimedokoreanin B (EK-B) B A 8 B 5 A 5 C 4 (0.084%) CML, CMA

5 EKB icaritin EKB 9 Kariu T., Nakao R., Ikeda T., Nakashima K., Potempa J., Imamura T., Inhibition of gingipains and Porphyromonas gingivalis growth and biofilm formation by prenyl flavonoids. Journal of periodontal research,, 52 (1), 2017, DOI: /jre Sugawa H., Ohno R., Shirakawa J., Nakajima A., Kanagawa A., Hirata T., Ikeda T., Moroishi N., Nagai M., Nagai R., Eucommia ulmoides extracts prevent the formation of advanced glycation end products. Food Funct.,, 7 (6), 2016, DOI: /C5FO01563D Nakashima K., Miyashita H., Yoshimitsu H., Fujiwara Y., Nagai R., Ikeda T., Two new prenylflavonoids from Epimedii Herba and their inhibitory effects on advanced glycation end-products. J. Nat. Med.,, 70 (2), 2016, DOI: /s Usui K., Ikeda T., Horibe Y., Nakao M., Hoshino T., Mizushima T., Identification of HSP70-inducing activity in Arnica montana extract and purification and characterization of HSP70-inducers. J. Dermatol. Sci.,, 78 (1), 2015, DOI: /j.jdermsci 研究 ローズレッドについて Ikeda Tsuyoshi Prenylflavonoids from Epimedii Herba inhibits formation of advanced glycation end-products International conference on conservation of biodiversity and sustainable use of tropical and subtropical plants Guilin Plaza HotelGuilinChina AGEs AGEs AGEs AGEs AGEs ( ) IKEDA Tsuyoshi

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