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Plantagoside as Maillard reaction inhibitor—its inhibitory mechanism and application
International Congress Series 1245 (2002) 411 – 412
Plantagoside as Maillard reaction inhibitor—its inhibitory mechanism and application Nobuyasu Matsuura a,*, Chihiro Sasaki a, Tadashi Aradate a, Makoto Ubukata a, Hiroyuki Kojima b, Mitsuharu Ohara b, Junichi Hasegawa b a
Biotechnology Research Center, Toyama Prefectural University, 5180 Kosugi-machi, Imizu-gun, Toyama 939-0398, Japan b Ichimaru Pharcos Company, Limited, 318-1 Shinsei-cho, Motosu-gun, Gifu 501-0475, Japan
Abstract An improvement of the Maillard reaction inhibitor screening system was carried out and led to the decrease of the background on fluorescent analysis with which we were able to perform the efficient screening, separation and purification of active compounds. As a result, plantagoside (Pl) (5,7,4V,5V-tetrahydroxyflavanone-3V-O-glucoside) from the seed of Plantago asiatica was isolated as an active compound. Plantagoside (Pl: IC50 1.2 AM) was about 90 times more potent than aminoguanidine (AG) which has been reported as a Maillard reaction inhibitor. We report on the structure – activity relationship, the effect for decline of an enzyme function by glycation and site and mechanism of action. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Inhibitor; Flavonoid; Plantagoside; Superoxide dismutase; Inhibitory mechanism
Only a few compounds, i.e. aminoguanidine (AG) and its derivatives, have been reported as Maillard reaction inhibitors. Thus, the screening for new Maillard reaction inhibitors from plant extracts was carried out. A fluorometric analysis of advanced glycation endproducts (AGEs) was applied to detection of the inhibitory activity. An improvement of the screening system led to the decrease of the background on fluorescent analysis with which we were able to perform the efficient screening, separation and purification of active compounds. As a result, plantagoside (Pl) (5,7,4V,5V-tetrahydroxy*
Corresponding author. Tel.: +81-766-56-7500; fax: +81-766-56-2498. E-mail address: [email protected] (N. Matsuura).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 2 ) 0 0 9 6 0 - 3
412
N. Matsuura et al. / International Congress Series 1245 (2002) 411–412
flavanone-3V-O-glucoside) from the seed of Plantago asiatica was isolated as an active compound. Plantagoside (Pl: IC50 1.2 AM) was about 90 times more potent than AG, and it was also clarified that glycation-derived cross-link of protein was inhibited. We report that (1) the structure –activity relationship, (2) site and mechanism of action and (3) the effect for decline of an enzyme function by glycation. (1) The structure – activity relationship: Four kinds of compounds, whose oxidation pattern was the same, but whose fundamental skeleton was different, were prepared and their inhibitory activities were evaluated. The order of inhibitory activity was flavone > flavonolHflavanone>flavanonol, based on the difference of the fundamental skeleton. (2) Site and mechanism of action: The inhibitory activity of Pl for each reaction step (condensation of glucose with protein, and generation of Amadori compound) in the early stage was examined. However, only the weak inhibitory activities for both steps were detected. The result suggested that Pl had little effect in the early stage. Hence, it seems that Pl mainly inhibits the late stage of the Maillard reaction. In addition, the structural change of Pl under the reaction conditions was examined. The result showed that Pl was decomposed into the chromone corresponding to the A and C ring of flavonoid skeleton and a putative 2,3-dihydroxybenzene-1V-O-glucoside (DHG) corresponding to the B ring of its skeleton, and the chromone showed the inhibitory activity by combining with the glucose. Although the structure of the unstable DHG could be isolated, one standard sample of DHG derivatives, 1V,2V,3V-trihydroxybenzene, inhibited the late stage of the Maillard reaction. (3) The effect for decline of an enzyme function by glycation: It is known that the enzymatic activity of superoxide dismutase (SOD) is declined by glycation. Thus, we evaluated the effect of Pl for the loss of the enzyme function. It was clarified that lowering of the SOD activity by glycation was suppressed by about 40% by addition of Pl at the low concentration of 3.1 –12.5 AM.
Plantagoside as Maillard reaction inhibitor—its inhibitory mechanism and application Nobuyasu Matsuura a,*, Chihiro Sasaki a, Tadashi Aradate a, Makoto Ubukata a, Hiroyuki Kojima b, Mitsuharu Ohara b, Junichi Hasegawa b a
Biotechnology Research Center, Toyama Prefectural University, 5180 Kosugi-machi, Imizu-gun, Toyama 939-0398, Japan b Ichimaru Pharcos Company, Limited, 318-1 Shinsei-cho, Motosu-gun, Gifu 501-0475, Japan
Abstract An improvement of the Maillard reaction inhibitor screening system was carried out and led to the decrease of the background on fluorescent analysis with which we were able to perform the efficient screening, separation and purification of active compounds. As a result, plantagoside (Pl) (5,7,4V,5V-tetrahydroxyflavanone-3V-O-glucoside) from the seed of Plantago asiatica was isolated as an active compound. Plantagoside (Pl: IC50 1.2 AM) was about 90 times more potent than aminoguanidine (AG) which has been reported as a Maillard reaction inhibitor. We report on the structure – activity relationship, the effect for decline of an enzyme function by glycation and site and mechanism of action. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Inhibitor; Flavonoid; Plantagoside; Superoxide dismutase; Inhibitory mechanism
Only a few compounds, i.e. aminoguanidine (AG) and its derivatives, have been reported as Maillard reaction inhibitors. Thus, the screening for new Maillard reaction inhibitors from plant extracts was carried out. A fluorometric analysis of advanced glycation endproducts (AGEs) was applied to detection of the inhibitory activity. An improvement of the screening system led to the decrease of the background on fluorescent analysis with which we were able to perform the efficient screening, separation and purification of active compounds. As a result, plantagoside (Pl) (5,7,4V,5V-tetrahydroxy*
Corresponding author. Tel.: +81-766-56-7500; fax: +81-766-56-2498. E-mail address: [email protected] (N. Matsuura).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 2 ) 0 0 9 6 0 - 3
412
N. Matsuura et al. / International Congress Series 1245 (2002) 411–412
flavanone-3V-O-glucoside) from the seed of Plantago asiatica was isolated as an active compound. Plantagoside (Pl: IC50 1.2 AM) was about 90 times more potent than AG, and it was also clarified that glycation-derived cross-link of protein was inhibited. We report that (1) the structure –activity relationship, (2) site and mechanism of action and (3) the effect for decline of an enzyme function by glycation. (1) The structure – activity relationship: Four kinds of compounds, whose oxidation pattern was the same, but whose fundamental skeleton was different, were prepared and their inhibitory activities were evaluated. The order of inhibitory activity was flavone > flavonolHflavanone>flavanonol, based on the difference of the fundamental skeleton. (2) Site and mechanism of action: The inhibitory activity of Pl for each reaction step (condensation of glucose with protein, and generation of Amadori compound) in the early stage was examined. However, only the weak inhibitory activities for both steps were detected. The result suggested that Pl had little effect in the early stage. Hence, it seems that Pl mainly inhibits the late stage of the Maillard reaction. In addition, the structural change of Pl under the reaction conditions was examined. The result showed that Pl was decomposed into the chromone corresponding to the A and C ring of flavonoid skeleton and a putative 2,3-dihydroxybenzene-1V-O-glucoside (DHG) corresponding to the B ring of its skeleton, and the chromone showed the inhibitory activity by combining with the glucose. Although the structure of the unstable DHG could be isolated, one standard sample of DHG derivatives, 1V,2V,3V-trihydroxybenzene, inhibited the late stage of the Maillard reaction. (3) The effect for decline of an enzyme function by glycation: It is known that the enzymatic activity of superoxide dismutase (SOD) is declined by glycation. Thus, we evaluated the effect of Pl for the loss of the enzyme function. It was clarified that lowering of the SOD activity by glycation was suppressed by about 40% by addition of Pl at the low concentration of 3.1 –12.5 AM.