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1 ver. 4.3 HS
2 14 1, ) 2) 1
3 24% p- 45 1) Schwab D. et al., Hepatic uptake of synthetic chlorogenic acid derivatives by the organic anion transport proteins. J. Pharmacol. Exp. Ther. 296, 91-8 (2001). 2) Moon J. K. et al., Role of roasting conditions in the level of chlorogenic acid content in coffee beans: correlation with coffee acidity. J. Agric. Food Chem. 57, (2009) *) * Fukushima Y. et al., Coffee and green tea as a large source of antioxidant polyphenols in the Japanese population. J. Agric. Food Chem., 57, (2009). 2 2
4 Pellegrini N., et al., Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays. J. Nutr. 133, (2003). 3 1) 2) 1) Tverdal A., et al., Coffee intake and mortality from liver cirrhosis. Ann. Epidemiol. 13, (2003). 2) Inoue M., et al., Effect of coffee and green tea consumption on the risk of liver cancer: cohort analysis by hepatitis virus infection status. Cancer Epidemiol. Biomarkers Prev. 18, (2009). 4HDL- HDL- HDL- Ehrlich A., et al., Effect of processed and non-processed coffee samples on gastric potential difference. Study with healthy male Helicobacter pylori-positive and Helicobacter pylori-negative volunteers. Arzneimittelforschung 49, (1999). 5 Inoue M., et al., Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan. Cancer Causes Control 9, (1998). Jiang Y., et al., Induction of cytotoxicity by chlorogenic acid in human oral tumor cell lines. Phytomedicine 7, (2000) Farah 3) mg 1520% 6 7 3
5 H H H 1 5 H R R=H: R=CH 3 : H H CH R=: H p- H H R 4 R=H: R=CH 3 : H 5 3 R=: H R 3 R=H: R=CH 3 : 4 H 3 R=: CH 3 CH 3 N N N N CH
6 1) 1 Naldini M., et al. Absorption of phenolic acids in humans after coffee consumption. J. Aglic. Food Chem. 50, (2002). 2) 2 lthof M.R., et al. Chlorogenic acid and caffeic acid are absorbed in humans. J. Nutr. 131, (2001). 3) 3 Farah A., et al. Chlorogenic acids from green coffee extract are highly bioavailable in humans. J. Nutr. 138, (2008). 4) -6-in vitro Arion W.J., et al. Chlorogenic acid and hydroxynitrobenzaldehyde:new inhibitors of hepatic glucose 6-phosphatase. Arch. Biochem. Biophys. 339, (1997). 5) in vitro (2001). 6) Adidoff M.T., et al. Special clinical report for Russian Ministry of health. Moscou, clinical report 12 (1999). 7) Greer F., et al. Caffeine ingestion decrease glucose disposal during a hyperinsulinemic-euglycemic clamp in sedentary humans. Diabetes 50, (2001). 8) Ryu S., et al. Caffeine as a lipolytic food component increases endurance performance in rats and athletes. J. Nutr. Sci. Vitaminol. 47, (2001). 9) Graham T.E., et al. Metabolic and exercise endurance effects of coffee and caffeine ingestion. J. Appl. Physiol. 85, (1998). 10) Hungu N., et al. Caffeine, carnitine and choline supplementation of rats decreases body fat and serum leptin concentration as dose exercise. J. Nutr. Physiol. 130, (2001). 11) a) Van Dam R.M., et al. Coffee consumption and risk of type 2 diabetes mellitus. Lancet 360, (2002)., b) Tuomilehto J., et al., Coffee consumption and risk of type 2 diabetes mellitus among middle aged Finnish men and woman. J. Am. Med. Assoc. 291, (2004). c) ba S., et al., Consumption of coffee, green tea, oolong tea, black tea, chocolate snacks and the caffeine content in relation to risk of diabetes in Japanese men and women. Br. J. Nutr. 103, (2010). 5
7 (1) in vivo p. 8 in vitro p. 9 (2) 3T3-L1 in vitro p. 9 in vivo p. 11 in vivo p. 14 in vivo p. 14 in vivo p. 18 (3) in vitro p. 19 in vivo p. 20 (4) UCP in vivo, p. 21 in vitro p. 22 CPTin vivo p. 22 (5) in vivo p. 24 -in vitro p. 25 in vitro, p. 26 (6) SD DPPH p. 27 6
8 7
9 4. (1) in vivo 2, 2. [n=6 p<0.01dunnett ] 20 ddy6 30 5w/v %10 ml/kg 1 5 ml/kg 24 6 E 8
10 in vitro in vitro 3 3. (n=2) SIGMA units/ml S (2) 3T3-L1 in vitro 3T3-L1 4 3-GPDH T3-L1 9
11 5. 3T3-L1 n=6-7 3T3-L cells/ml10% DMEM 2 1 g/ml0.25 M0.5 mm 2 1 g/ml GPDH 10
12 in vivo 10.0%27.0% 6 6. (n=6-7) 11
13 7 7. [n=7 p<0.05dunnett ] ddy % % % CE-2, 13 12
14 %11.6% 8 8. (n=6-7) 13
15 in vivo [n=6 p<0.01dunnett ] ddy w/v% 2 in vivo C57BL/6J % 1% 0.5% 1 14
16 (g) 10. n=6 1. (g) (g) (g) (g) 20.6± ± ± HF 21.0± ± ± HF+ 0.5% 23.6± ± ±0.7** 67.4 HF+ 1.0% 21.3± ±0.2* 1.9±0.2** 57.9 [n=6hf p<0.05, p<0.01dunnett ] 0.5 1% 0.5% 2 2. (g) (mg/g ) (g) (mg/g ) 0.30± ± ± ±1.0 HF 0.52± ± ± ±0.8 HF+ 0.5% 0.36± ± ±0.07* 37.1±2.3** HF+ 1.0% 0.26±0.02** 11.3±0.8** 1.00± ±0.9 [n=6hf p<0.05, p<0.01dunnett ] 15
17 %
18 % C57BL/6J CE %20%4% 3.5%1% 66.5% %20%10%13% 20%4%3.5% 1%28.5% 25 17
19 in vivo SD 4 1% 0.5% 0.125% AIN-93G Control (g) 143±2 142±3 g 386±10 303±14* g 244±9 161±12* g 22.7± ±1.0 g /g 0.40± ±0.02* g 24.5± ±1.5* (Liver/100 g ) 6.33± ±0.28 g 6.78± ±0.34* 5.01± ±0.28* g/100g 1.74± ±0.09* 1.28± ±0.06* (mg/dl) 75.6± ±3.2* (mg/dl) 27.7± ±1.0* mg/dl 180.3± ±11.7* mg/dl 184±13 193±9 LPnmol/mL 15.6± ±0.5* SD% 16.5± ±0.6 (nmol/min/mg protein) Fatty acid synthase 4.88± ±1.17* Carnitine palmitoyltransferase 4.12± ±0.34 Malic enzyme 19.3± ±1.49* Glucose-6-phosphate dehydrogenase 15.9± ±1.33 Phosphatidic acid phoshohydrolasemic Mg+ 4.34± ±0.42* Mg- 2.94± ±0.13 n=6*: p<0.05 Tanaka K., Nishizono S., Tamaru S., Kondo M., Shimoda H. Tanaka J., kada T. Anti-obesity and hypotriglyceridemic properties of coffee bean extact in SD rats. Food Sci. Technol. Res. 15, (2009).
20 (3) in vitro 1000 g/ml n=4 19
21 * *Tholon L, et al., An in vitro, ex vivo, and in vivo demonstration of the lipolytic effect of slimming liposomes: An unexpected 2 -adrenergic antagonism. J. Cosmet. Sci. 53, (2002). Wistar Medium F- in vivo ddy w/v%10 ml/kg 1 20
22 (4) UCPin vivo, UCP-1 UCP β 0 KK BAT UCP-1 60 mg/kg 4 UCP-1 mrna RT-PCR,- n=15,, *: p<0.05 Ref. ) Kogure A., et al., Effects of caffeine on the uncoupling protein family in obese yellow KK mice. Clin. Exp. Pharmacol. Physiol. 29, (2002) 21
23 in vitro 1000 g/ml CPTin vivo - CPT CPT 18 CPT CPT 3-22
24 18. CPT n=4-5,, *: p<
25 ddy7 CE-2, M 1 mm EDTA ph , 10 11, mlcpt DTNB *) *) Markwell M. A. K., et al., The subcellular distribution of carnitine acyltransferases in mammalian liver and kidney. J. Biol. Chem., 248, (1973). (5) in vivo mg/kg 200 mg/kg 19. [n=6 p<0.01dunnett ] 18 ddy6 10 ml/kg1 0.5 g/kg 2 g/kg5 ml/kg GL-E 24
26 -in vitro 酵阻害活性 ( % of Control ) 120 生コーヒー豆エキス 濃度 (μ g/ml) サンプル濃度 (μ g/ml) カフェ酸 サンプル濃度 (mg/ml) IC50 IC50 (g/ml) 70 > >
27 Sigma M ph mm 4- --D-Sigma DMS 4DMS 2 50 L/well25 L/well l/well mg protein/ml, 0.05 mm0.2 M Na 2 C 3 (100 l/well) 366 nm 450 nm in vitro, CHL 6- Lineweaver-Burk Glucose-6-P1-10 mm CHL mm Y 6- Slope Y Intercept 26
28 Y Ref.) Arion W.J., et al. Chlorogenic acid and hydroxynitrobenzaldehyde:new inhibitors of hepatic glucose 6-phosphatase. Arch. Biochem. Biophys. 339, (1997). (6) SD DPPH LDL- SD 1,1-2-DPPH 22 SD DPPH SD DPPH SD SD DPPH DPPH DPPH 27
29 %Lot. K320, 100 mg [6, ] BMI25%18 25% 18%20% BMI (kg/m 2 ) = (kg) / (m) / (m) () = [() / ] mg 4 2 t-p< mg/ 4 p= BMI mg/dl mg/dl( 24)6 p= p=
30 200 mg/ Ω mg/4 kg % BMIkg/m Ω (%) (%) cm cm p=0.12 / mm mg/dl p=0.13 mg/dl p=0.15 mg/dl meq/l mg/dl p=0.05 g/dl
31 mg/4 30
32 mg/4 BMI: >23 kg/m mg/ 8 BMI Park J. Y. et al., Korean J. Nutr., 43, (2010). 31
33 6. (1) % (2) ph ph 1 26 ph 100% 32
34 ph 4 ph ph mg 500 ml AB C () 33
35 7 2.2g/100g 29.2g/100g 1 0.3g/100g 10.2g/100g 58.1g/100g 2 352kcal/100g 3 0.5g/ mg/100g 1) ) ( ++++) 3) ; 9; 4; 2, , (1) P 447 (2) LD mg/kg ICR 5 14 LD mg/kg (3) 1 2% 4 34
36 2% (4) Ames test TA100TA1535TA98 TA1537WP2uvrA g/ml 2 (5) mg p p. 29 (6) (7) LD50 * kg mg mg 60 kg ** * ** WH P mg 35
37 10. 1) 2) 3) 4) 1) 2) 1) 2) 11 -P -PCR 5kg P -PCR INCI CFFEA RBUSTA SEED EXTRACT
38 24.0 % 45.0 % HPLC HPLC 10.0 % 1g1052 ) 1 30 ppm 2 1 ppm /g /g BGLB 100 % 2 37
39 25.0 % Folin-Denis 10.0 % 1g1052 ) 1 30 ppm ( 2 ) 2 1 ppm ( 3 ) /g /g BGLB 100% 2 38
40 TEL(0586) () FAX(0586) URL/ F TEL (03) FAX (03) * * * * -PCR PC
41 40
ver5.1 HS 1. ALPHA LIPOIC ACID () S S COOH HS 1. α - SH COOH - ( 1) CoA -( 2)- - --P80 (--WSP8-L1-WSPC8 -LC1) - 1
ORYZA OIL & FAT CHEMICAL CO., LTD. ALPHA LIPOIC ACID --P () --P80 () --WSP8 () --L1 () --PC () --PC80 () --WSPC8 () --LC1 () ver. 5.1HS ver5.1 HS 1. ALPHA LIPOIC ACID 16 3 31 0331009 - () 19 5 24 0524001
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RYZA IL & FAT CHEMICAL C., LTD. SAKURA EXTRACT Ver.1.4MK Ver. 1.4MK 1) 1300 1929 1 Ver. 1.4MK Sakura 1-caffeoyl---D-glucopyranoside quercetin 3---D-glucopyranoside 1) :, 4, 11-22 (1995). 2 Ver. 1.4MK 3
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ORYZA POLYAMINE ORYZA POLYAMINE -P -PC -LC 1. Ver.1.0 MM ver. 1.0MM 1) Roseeuw D.I. et al., Epidermal keratinocytes actively maintain their intracellular polyamine levels. Cell Tissue Kinet. 16, 493-504
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