Chapter 23
Some Biological Effects of Raspberry Ketone and Its Precursor
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Takeshi Ikemoto, Tomohiro Yokota, and Shintaro Inoue Basic Research Laboratory, Kanebo Cosmetics Inc., 3-28,5-Chome, Kotobuki-Cho, Odawara, Kanagawa 250-0002 Japan
Naturalfragrantchemicals have been screened for their potential uses as alternatives such as antimicrobials and antioxidants. Recently, glycosidically bound volatiles have been studied as fragrant precursors in essential oil plants and have also been the subject of interest in various industries. Raspberry ketone (RK; 4-(p-hydroxyphenyl)-2-butanone) is well known as a typical aroma chemical of red raspberry (Rubus idaeus), and its β-Dglucoside (RaG) has been isolated as its precursor. RK has a similar structure to capsaicin, a compound known to exert an anti-obesity action. We confirmed that RK accelerated lipolysis in vitro more potently than capsaicin and prevented high-fat diet (HFD)-induced elevations in body and liver weights. We found that RaG inhibited melanin synthesis more than hydroquinone βD-glucoside (arbutin), a compound that is already used as a melanin inhibitor in cosmetics.
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© 2008 American Chemical Society In Food Flavor; Tamura, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2008.
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267 Essential oils have provoked interest as sources of natural fragrant chemicals and some of them such as eugenolfromclove buds and wo-eugenol from nutmeg have been screened for potential uses as antimicrobials and antioxidants (7). Capsaicin (A^-[(4-hydroxy-3-methoxyphenyl)-methyl]-8-methyl6-nonamide), a pungent principle of hot red pepper, is known to exert an antiobesity action. Fragrant chemicals and spice ingredients have been subjects of interest not only in food industries but also in pharmaceutical and cosmetics companies. Raspberry ketone (RK; 4-(p-hydroxyphenyl)-2-butanone), a typical aroma chemical of red raspberry, is mainly used by flavorists (Figure 1). RK has GRAS (Generally Recognized As Safe) status and was also on the list of artificial flavoring substances given by the Council of Europe. Its world consumption for all uses is estimated at over 10,000 kg per year (2). We expected that RK might influence lipid metabolism in ways similar to capsaicin due to its structural similarity. In this study, the effects of RK on obesity and lipid metabolism are discussed. Numerous glycosidically bound volatiles (GBVs) have been isolated from flowers,fruitsand tea leaves (5). GBVs have been known to be flavoring and fragrance precursors, and have been the subject of interest in the food, tobacco and wine industries. Arbutin (hydroquinone /?-D-glucoside), isolatedfromthe leaves of Arctostaphylos uva-ursi, is widely used in skin care cosmetics as a tyrosinase inhibitor (4). However, there is little discussion about the effects of other glycoside derivatives. The depigmentation activity of several GBVs, especially raspberry ketone /?-D-glucoside, in cultured B16 melanoma cells are discussed.
0
Raspberry ketone (RK)
OH
Raspberry ketone /J-D-glucoside (RaG)
OH
Capsaicin
Arbutin
Figure 1. Structures of Raspberry ketone and its P-D-glucoside.
In Food Flavor; Tamura, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2008.
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Anti-obesity Action of Raspberry Ketone
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Effect of RK on Norepinephrine-Induced Lipolysis and Localization of HSL in White Adipocytes To compare the effects of RK and capsaicin on norepinephrine-induced lipolysis, the following in vitro examination was performed. Young male Crj: Wistar rats were sacrificed by cervical dislocation to minimize endogenous catecholamine secretion, and their epididymal adipose tissues were quickly removed. Isolated fat cells were obtainedfromthe removed epididymal adipose tissue by the method of Rodbell (5). The fat cells were incubated at 37°C for lh in Hanks' buffer (pH 7.4) supplemented with 2.5% (w/v) bovine serum albumin and the indicated concentrations of each sample and norepinephrine. After incubation, the reaction mixture was centrifiiged to separate the medium and fat cells. The free fatty acids (FFAs) contents of the medium was estimated by the method of Warnick (6). It was observed that 10" M of capsaicin and RK increased norepinephrineinduced lipolysis though the effect was only significant with RK (Figure 2). RK enhanced FFAs release by fat cells in a dose-dependent manner (Figure 3). RK significantly increased the amount of hormone-sensitive lipase protein (HSL, 84kDa) in the fat layer and concominantly reduced the amount in the supernatant. We also confirmed that RK didn't enhance HSL activity at the same concentration (data not shown). Morimoto et al. (7) reported that the conversion of HSL translocation to its substrate on the surfaces of lipid droplets is a crucial step for triacylglycerol hydrolysis. The results suggest that RK enhances norepinephrineinduced lipolysis but not via HSL activation. 3
1. No addition 2. Control (0.01 fig/ml NE ) 3. NE + Capsaicin 10 M 4. NE + R K 10 M 3
3
•a E
Figure 2. Effect ofraspberry ketone and capsaicin on lipolysis. Lipolysis was expressed asfreefatty acids mEq/mL packed fat cells per h. * *p
