Inhibition of advanced glycation end product formation on collagen by rutin and its metabolites

Inhibition of advanced glycation end product formation on collagen by rutin and its metabolites
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DOI:
10.1016/j.jnutbio.2005.10.002
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发表时间:
2006-08-01
影响因子:
5.6
通讯作者:
Boissonneault, Gilbert A.
Boissonneault, Gilbert A.
中科院分区:
医学2区
文献类型:
--
作者:
Cervantes-Laurean, Daniel;Schramm, Derek D.;Boissonneault, Gilbert A.

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一些证据表明,水果和蔬菜中的类黄酮芦丁或其代谢产物之一可以有效地调节晚期糖基化终产物(AGE)的形成。摄入后,芦丁形成代谢物,包括3,4-二羟基苯乙酸(3,4-DHPAA)、3,4-二羟基甲苯(3,4-DHT)、间羟基苯乙酸(m-HPAA)、3-甲氧基-4-羟基苯乙酸(香草酸,HVA)和3,5,7,3 ',5'-五羟基黄酮醇(槲皮素)。我们研究了芦丁及其代谢产物对AGE生物标志物形成的影响,如戊糖苷,胶原蛋白相关荧光,N-α-羧甲基赖氨酸(CML)加合物,葡萄糖自氧化和胶原蛋白糖化,使用体外模型,其中胶原蛋白I与葡萄糖孵育。含有邻苯二甲酸二羟基的RbR代谢物,即,3,4-DHT、3,4-DHPAA和槲皮素以剂量依赖性方式抑制戊糖苷和荧光加合物的形成、葡萄糖自氧化和胶原蛋白I的糖化,而不含邻苯二甲酸二羟基的代谢物,即,HVA和m-HPAA的效果要差得多。芦丁的所有五种代谢产物都有效地抑制CML的形成。相反,在糖化和荧光AGE产物积累的初始阶段,只有含邻苯二酚羟基的芦丁代谢产物有效。这些研究表明,芦丁和循环代谢产物的芦丁可以抑制早期糖基化产物的形成,包括荧光和非荧光AGEs诱导的葡萄糖基化的胶原蛋白I在体外。这些影响可能有助于与食用芸香苷相关的有益健康影响。(c)2006爱思唯尔公司All rights reserved.
Several lines of evidence suggest that rutin, flavonoid in fruits and vegetables, or one of its metabolites may effectively modulate advanced glycation end product (AGE) formation. Following ingestion, rutin forms metabolites that include 3,4-dihydroxyphenylacetic acid (3,4-DHPAA), 3,4-dihydroxytoluene (3,4-DHT), m-hydroxyphenylacetic acid (m-HPAA), 3-methoxy-4-hydroxyphenylacetic acid (home-vanillic acid, HVA) and 3,5,7,3',5'-pentahydroxyflavonol (quercetin). We studied the effects of rutin and its metabolites on the formation of AGE biomarkers such as pentosidine, collagen-linked fluorescence, N-epsilon-carboxymethyllysine (CML) adducts, glucose autoxidation and collagen glycation, using an in vitro model where collagen I was incubated with glucose. Rutin metabolites containing vicinyl dihydroxyl groups, i.e., 3,4-DHT, 3,4-DHPAA and quercetin, inhibited the formation of pentosidine and fluorescent adducts, glucose autoxidation and glycation of collagen I in a dose-dependent manner, whereas non-vicinyl dihydroxyl group-containing metabolites, i.e., HVA and m-HPAA, were much less effective. All five metabolites of rutin effectively inhibited CML formation. In contrast, during the initial stages of glycation and fluorescent AGE product accumulation, only vicinyl hydroxyl group-containing rutin metabolites were effective. These studies demonstrate that rutin and circulating metabolites of rutin can inhibit early glycation product formation, including both fluorescent and nonfluorescent AGEs induced by glucose glycation of collagen I in vitro. These effects likely contribute to the beneficial health effects associated with rutin consumption. (c) 2006 Elsevier Inc. All rights reserved.