Metabolic effects of silibinin in the rat liver
Metabolic effects of silibinin in the rat liver
复制标题
DOI：
10.1016/j.cbi.2011.11.006
复制
发表时间：
2012-01-25
影响因子：
5.1
通讯作者：
Constantin, Jorgete
中科院分区：
文献类型：
--
作者：
Colturato, Carina Parisoto;Constantin, Rodrigo Polimeni;Constantin, Jorgete
黄酮木脂素水飞蓟宾是两种非对映异构体水飞蓟宾 A 和水飞蓟宾 B 的混合物，是从杂色水飞蓟 (Silybum marianum (L) Gaertn. (Asteraceae)) 的果实和种子中提取的成分，称为水飞蓟素。在水飞蓟宾的治疗特性中，其抗高血糖作用已被广泛探索。水飞蓟宾在结构上与类黄酮槲皮素和非瑟酮相关，此前已证明它们对与血糖调节相关的肝脏代谢过程非常活跃。目前工作的目的是研究水飞蓟宾对灌注大鼠肝脏中负责维持血糖的代谢途径的影响，特别是糖原分解和糖异生。还检查了这些途径中一些关键酶的活性以及对分离线粒体中能量代谢参数的影响。在50-300μM的浓度范围内，水飞蓟宾在禁食条件下抑制糖异生，并在进食条件下抑制糖原分解和糖酵解。水飞蓟宾发挥这些作用的机制是多重且复杂的。它抑制葡萄糖6-磷酸酶的活性，抑制丙酮酸载体，降低线粒体能量转导效率。它还可以通过其促氧化作用减少糖异生和线粒体的 NADH 供应。一般来说，水飞蓟宾的作用和效力与槲皮素和非瑟酮相似。然而，水飞蓟宾发挥了一些独特的作用，例如对进食条件下耗氧量的抑制作用以及灌注肝脏能量状态的变化。可以得出结论，水飞蓟宾对肝脏葡萄糖代谢的影响可以解释其降血糖特性。然而，这种效应在一定程度上是继发于细胞能量代谢受损的，这一发现在其治疗用途中应予以考虑。 (C) 2011 Elsevier Ireland Ltd. 保留所有权利。
The flavonolignan silibinin, which is a mixture of two diastereoisomers, silybin A and silybin B, is a component of the extract obtained from the fruit and seeds of the variegated milk thistle (Silybum marianum (L) Gaertn. (Asteraceae)), known as silymarin. Among the therapeutic properties credited to silibinin, its antihyperglycaemic action has been extensively explored. Silibinin is structurally related to the flavonoids quercetin and fisetin, which have been previously demonstrated to be very active on liver metabolic processes related to glycaemic regulation. The aim of the present work was to investigate the effects of silibinin on metabolic pathways responsible for the maintenance of glycaemia, particularly glycogenolysis and gluconeogenesis, in the perfused rat liver. The activities of some key enzymes in these pathways and on parameters of energy metabolism in isolated mitochondria were also examined. At a concentration range of 50-300 mu M, silibinin inhibited gluconeogenesis in the fasted condition and inhibited glycogenolysis and glycolysis in the fed condition. The mechanisms by which silibinin exerted these actions were multiple and complex. It inhibited the activity of glucose 6-phosphatase, inhibited the pyruvate carrier, and reduced the efficiency of mitochondrial energy transduction. It can also act by reducing the supply of NADH for gluconeogenesis and mitochondria through its pro-oxidative actions. In general, the effects and the potency of silibinin were similar to those of quercetin and fisetin. However, silibinin exerted some distinct effects such as the inhibitory effect on oxygen consumption in the fed condition and a change in the energy status of the perfused livers. It can be concluded that the effects of silibinin on liver glucose metabolism may explain its antihyperglycaemic property. However, this effect was, in part, secondary to impairment in cellular energy metabolism, a finding that should be considered in its therapeutic usage. (C) 2011 Elsevier Ireland Ltd. All rights reserved.